The 200th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened virtually at 10:30 a.m. on Monday, January 31, 2022. Dr. Anthony S. Fauci, director, National Institute of Allergy and Infectious Diseases (NIAID) presided as chair.
In accordance with the provisions of Public Law 92-463, the meeting was open to the public from 10:30 a.m. to 11:38 a.m. and from 1:00 p.m. to 4:32 p.m. The meeting was closed to the public from 8:00 a.m. to 10:30 a.m. and from 11:45 a.m. to 12:00 noon for review and consideration of individual grant applications. Notice of the meeting was published in the Federal Register.
Meeting Attendees
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Table of Contents
I. Review of Grant Applications
II. Remarks of the Director, NIAID—Anthony S. Fauci, M.D.
III. Guest Speaker—Lyric Jorgenson, Ph.D., acting NIH associate director for science policy, and acting director, NIH Office of Science Policy
IV. Report of the Allergy, Immunology, and Transplantation Subcommittee–Daniel Rotrosen, M.D., director, DAIT
V. Report of the Microbiology and Infectious Diseases Subcommittee–Emily Erbelding, M.D., M.P.H., director, DMID
VI. Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)–Carl Dieffenbach, Ph.D., director, DAIDS
VII. Adjournment
I. Review of Grant Applications
The National Advisory Allergy and Infectious Diseases Council convened in closed session to consider applications in allergy and immunology, microbiology and infectious diseases, and AIDS.
Funding Actions: The Council reviewed 5,495 research and training applications with primary assignment to NIAID for a requested amount of $1,782,675,802 in first-year direct costs and recommended approval of 2,821 applications with $1,019,987,480 in first-year direct costs.
II. Remarks of the Director, NIAID—Anthony S. Fauci, M.D.
Dr. Fauci opened the Council session by welcoming visitors to the meeting. He introduced a new Council member: Dr. Keith Jerome, professor in the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center, and professor and head of the Virology Division in the Department of Laboratory Medicine and Pathology at the University of Washington. Dr. Fauci also introduced two Division of Allergy, Immunology, and Transplantation (DAIT) ad hoc members: Dr. Rafi Ahmed, director of the Vaccine Center in the Department of Microbiology and Immunology at Emory University, and Dr. Julie McElrath, director of the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center.
Consideration of Minutes of Previous Meeting
Council considered the minutes of the September 13, 2021 meeting and concepts that had been presented and approved them as written.
Staff and Organizational Changes
Dr. Fauci announced appointments and transitions that have taken place since the last Council meeting.
In December, Dr. Francis Collins stepped down as NIH director after serving for more than 12 years under three U.S. presidents, which makes him the longest serving presidentially appointed NIH director. Dr. Larry Tabak will serve as acting NIH director, and Dr. Tara Schwetz will serve as acting NIH principal deputy director.
Dr. Shelma Middleton Little has been named acting director of NIH’s Office of Equity, Diversity, and Inclusion.
President Biden has nominated Dr. Robert Califf to be FDA commissioner.
In the Division of AIDS, Dr. Fatima Jones has been appointed chief of the Drug Development and Clinical Sciences Branch in the Therapeutics Research Program.
Dr. Masaru Kanekiyo has been selected as chief of the Vaccine Research Center’s (VRC) new Molecular ImmunoEngineering Section and Respiratory Viruses Core.
Dr. Carolina Barillas-Mury is the new chief of the Laboratory of Malaria and Vector Research in the Division of Intramural Research.
Tributes and Awards
In December, Drs. Kizzmekia Corbett, Barney Graham, Drew Weissman, and Katalin Kariko were named TIME Heroes of the Year for their groundbreaking work on the development of mRNA vaccines for COVID-19.
Meetings and Events
On November 4, HHS Secretary Xavier Becerra and Deputy Secretary Andrea Palm visited the VRC. During their visit, they took a laboratory tour and received an overview of VRC’s efforts to develop the NIH-Moderna mRNA COVID-19 vaccine and NIAID’s broader pandemic preparedness goals for future disease outbreaks.
Later in November, Dr. Fauci participated in the White House Tribal Nations Summit. Chairwoman Victoria Kitcheyan of the Winnebago Tribe of Nebraska moderated the Summit session that focused on the Biden Administration’s response to COVID-19.
On December 2, President Biden visited NIH to discuss the nation’s new strategy against the pandemic.
Dr. Fauci reported on virtual meetings that have been held with international delegations and health officials, including UK’s Chief Medical Officer, Quebec’s Minister of Health and Social Services, Minister of Health of the Republic of Indonesia, and the Minister of Health for Poland.
In September, Dr. Fauci provided virtual remarks to the fourth India-U.S. Health Dialogue in New Delhi, India. Dr. Fauci and Dr. Balram Bhargava, Director General of the Indian Council of Medical Research, virtually co-signed a Memorandum of Understanding that renewed the Indo-U.S. International Center of Excellence in Research Program.
Budget Update
NIAID is operating under a continuing resolution set to expire on February 18, 2022. The House and Senate are working to reach an agreement on the fiscal year (FY) 2022 annual appropriation.
The proposed overall increase for NIH is 15.1 percent under the House bill and 11.6 percent under the Senate bill. NIAID would receive an 8.0 percent increase under the House bill and a 4.5 percent increase under the Senate bill. Most of the increases are earmarked for research on universal flu vaccine, rapid vaccine platform technologies, and other disease-specific areas, therefore the actual budget increase available for new research programs is 4.0 percent in the House bill and 2.5 percent in the Senate bill.
Dr. Fauci summarized NIAID’s FY 2022 financial management plan. Our R01 payline is set at the 10 percentile for established principal investigators (PIs) and the 14 percentile for new PIs. NIAID does not plan to make programmatic cuts to noncompeting and competing grants. Competing research initiatives were cut up to 20 percent from their planned budget level. Our estimated success rates for research project grants will be 18 to 22 percent.
Dr. Fauci gave an overview of the funding NIAID received through two emergency supplemental funding packages: the Coronavirus Aid, Relief, and Economic Security (CARES) Act and the Coronavirus Preparedness and Response Supplemental Appropriations Act. The emergency supplemental funding provided NIAID with $1.5 billion and is available until September 30, 2024.
NIAID has provided $1.23 billion in support of extramural and intramural investigators to address the scientific areas that are most critical to understanding COVID-19 and advancing medical countermeasures. The remaining $307 million will be awarded to address the most urgent public health and scientific research needs. A significant portion of the remainder has been committed to support ongoing extramural and intramural projects, and infrastructure needs at the VRC in Bethesda and Rocky Mountain Laboratories in Hamilton, Montana.
Other NIH institutes collectively received $3.3 billion as part of a broader comprehensive response to the pandemic. This money supports initiatives such as 1) Researching COVID to Enhance Recovery (RECOVER), which aims to quickly improve our understanding of recovery after SARS-CoV-2 infection and to prevent and treat long COVID, and 2) Rapid Acceleration of Diagnostics (RADx), which is designed to speed innovation in the development, commercialization, and implementation of technologies for COVID-19 testing.
Additionally, HHS provided supplemental funding to support advanced development of medical countermeasures and additional funding for the Antiviral Program for Pandemics.
Legislative Update
On November 4, Dr. Fauci testified at a Senate Health, Education, Labor, and Pensions (HELP) Committee hearing titled “Next Steps: The Road Ahead for the COVID-19 Response.” The hearing provided an important opportunity to discuss the crucial role NIAID continues to play in the federal response to the pandemic and the work being done to develop additional therapeutics and next-generation vaccines, and to better understand the underlying mechanism of COVID-19 disease and the immune response to SARS-CoV-2 infection and vaccination.
On January 11, Dr. Fauci testified again before the Senate HELP Committee about the federal response to COVID-19 and efforts to address the Omicron variant. He also discussed work being done to prepare for the next pandemic through developing pan-coronavirus vaccines and participating in the Antiviral Program for Pandemics.
Dr. Fauci participated in numerous briefings with members of the Senate and House of Representatives that focused on what we know about how prior COVID-19 infection, vaccination, and boosters contribute to a person’s level of protection, as well as the need to develop better therapeutics and more durable and broadly protective vaccines.
On November 9, Dr. Fauci participated in a townhall meeting with Representative Anna Eshoo, chair of the House Energy and Commerce Subcommittee on Health, which focused on the impact of the COVID-19 pandemic and the ongoing federal response.
Dr. Fauci thanked NIAID staff who participated in many briefings and events on his behalf.
Other Information Items
Dr. Fauci began by presenting the most recent global and U.S. HIV/AIDS statistics. He noted that NIH has made awards to support HIV epidemic research teams working in U.S. communities. Awards will support implementation science research to advance the goals of Ending the HIV Epidemic in the United States, which aims to reduce new HIV infections in the United States by at least 90 percent by 2030.
He then continued with a COVID-19 update, summarizing the number of COVID-19 cases and deaths globally and in the United States. As of January 26, 2022, there were over 357 million cases and 5.6 million deaths globally, with more than 72 million of those cases and over 870,000 deaths in the United States.
On November 8 and 9, 2021, NIAID held a Workshop on Pandemic Preparedness: The Prototype Pathogen Approach To Accelerate Medical Countermeasures – Vaccines and Monoclonal Antibodies, where experts summarized current knowledge of the basic and translational research landscape, described research and intervention gaps, and proposed suitable prototype pathogens for further study and medical countermeasure development.
Dr. Fauci mentioned findings of a recent study on lung injury in COVID-19 that could help predict severe and prolonged COVID-19 cases and inform effective treatments. NIAID and Children’s National Hospital in Washington, D.C., are collaborating on a long-term study that will follow 1,000 children and young adults over three years and evaluate the impact of COVID-19 on their physical and mental health.
In December 2021, the FDA granted Emergency Use Authorization for two oral antivirals, Paxlovid and Molnupiravir, to treat COVID-19. The FDA also expanded the use of Remdesivir for use in outpatients with mild-to-moderate COVID-19 disease.
Dr. Fauci gave a summary of the SARS-CoV-2 variants of concern that have been documented over the course of the pandemic. The Omicron variant has many more mutations than the Delta variant, with key concerns being transmissibility, severity of disease, vaccine/evasion of immunity, and effectiveness of therapeutics. He stressed the need for a universal pan-coronavirus vaccine and noted that between September 2021 and January 2022 NIAID awarded $42.8 million to four academic institutions for research to develop vaccines to protect against multiple types of coronaviruses and viral variants.
Dr. Fauci concluded with updates on promising research of an mRNA vaccine that induced tick resistance and prevented transmission of Lyme disease, an oral immunotherapy for children one to three years old that induces remission of peanut allergy, and a breakthrough in transplantation with the first functional pig-to-human heart transplant.
III. Guest Speaker—Lyric Jorgenson, Ph.D., acting NIH associate director for science policy, and acting director, NIH Office of Science Policy
Dr. Lyric Jorgenson provided an update on plans to implement the new NIH Policy for Data Management and Sharing, which goes into effect on January 25, 2023.
Dr. Jorgenson noted that NIH has been working to facilitate data stewardship efforts and explained that data sharing helps advance rigorous and reproducible science, which enables research results to be validated and replicated, makes high-value datasets accessible, accelerates future research directions, and increases opportunities for citation and collaboration. Data sharing also promotes public trust in research by fostering transparency and accountability, demonstrating stewardship over taxpayer funds, maximizing research participants’ contributions, and supporting appropriate protections of research participants’ data.
Two significant requirements of the Policy are: a data management and sharing plan must be submitted to NIH with an application for funding and, if an application is funded, complying with the approved data management and sharing plan.
The Policy covers all NIH-supported research generating scientific data of sufficient quality to validate and replicate research findings, regardless of whether the data are used to support scholarly publications. Dr. Jorgenson clarified that the Policy says all data should be managed, but not all data need to be shared. Sharing data is expected to be the default; however, NIH recognizes that there may be justifiable reasons for not sharing data. Data should be shared no later than the time of research publication or, for unpublished data, at the end of the grant award.
Peer reviewers will evaluate the budget component of data management and sharing plans, and NIH program staff will assess plans. As projects progress, plans can be updated. Once an award is made, compliance with the approved plan will become a term and condition of award, and the plan will be monitored through regular reporting intervals.
Current resources that explain and provide information about the new Policy are available and include a recent blog post, supplemental information regarding responsible data management of American Indian and Alaska Native participant data, and a frequently asked questions (FAQs) page. More comprehensive guidance in the form of FAQs, additional supplemental information on topics of interest, and sample data management sharing plans are being developed, along with educational resources such as webinars.
IV. Report of the Allergy, Immunology, and Transplantation Subcommittee–Daniel Rotrosen, M.D., director, DAIT
Dr. Rotrosen welcomed the subcommittee members to the 200th meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting.
Dr. Rotrosen presented the following scientific and Division activities:
Staff and Organizational Changes
Amaziah Coleman, M.D., Dr. Coleman joined the Allergy, Asthma, and Airway Biology Branch in September 2021 as a medical officer. She received an M.D. degree from the University of Mississippi Medical Center. She completed her pediatrics residency training at Arkansas Children’s Hospital and her allergy and immunology fellowship at the University of Wisconsin-Madison. After fellowship, Dr. Coleman worked as an assistant professor at Children’s National Hospital in Washington, DC. During her fellowship and as faculty at Children’s National, she participated as a sub-investigator in multiple clinical trials focused on asthma, food allergy, and other atopic diseases. She is particularly passionate about improving health equity among individuals with allergic and immune disorders.
Olivia Molinar-Inglis, Ph.D., Dr. Molinar-Inglis joined the Radiation and Nuclear Countermeasures Program as an AAAS Science and Technology Fellow and program officer in August 2021. Through grants and contracts management, she will secure and foster collaborations with industry, academia, and government to advance the development or repurposing of drugs and diagnostic technologies for use during a radiation emergency. Dr. Molinar-Inglis completed her B.S. in microbiology at the University of Texas at El Paso and completed her Ph.D. in biological sciences at Carnegie Mellon University, where she focused on investigating the role of a colon cancer tumor suppressor in cytoskeletal rearrangements. During her postdoctoral studies in the Pharmacology Department at the University of California, San Diego, she investigated G protein-coupled receptor signaling in vascular integrity and inflammation in sepsis through an NIH-funded Institutional Research and Academic Career Development Award and UC President’s Postdoctoral Fellowships. In addition to her work as a scientist, Dr. Molinar-Inglis is an educator and advocate in diversity, equity, and inclusion.
Brittney Penn, Ms. Penn joined the Office of Regulatory Affairs as a quality assurance specialist in January 2022. Ms. Penn completed her B.S. in biological sciences at Kean University. She has professional experience in quality and compliance from companies such as Stokes Pharmacy and Janssen Pharmaceuticals. She also comes with laboratory experience from the American Red Cross and New Jersey Public Health and Environmental Laboratories.
Melissa Greenleaf, R.N., B.S.N., CCRC, Ms. Greenleaf joined the Autoimmunity and Mucosal Immunology Branch as a project manager in January 2022. Ms. Greenleaf completed her Bachelor of Science degree in Public and Community Health from the University of Maryland and received her Bachelor of Science in Nursing degree from Chamberlain College of Nursing. She has worked as a clinical nurse in cardiac care and the ICU. Most recently she has spent the last eight years at the Walter Reed Army Institute or Research in Silver Spring, Maryland, working as a study coordinator and clinical manager working on Phase I/II infectious disease vaccine trials for various branches of the military.
Selected Funding Opportunities
NIAID
SUNBEAM - Analysis and Bioinformatics Center (ABC) (UM1, Clinical Trial Not Allowed) RFA-AI-21-060: Posted on September 21, 2021, the purpose of this funding opportunity announcement (FOA) is to establish a mechanistic omics center (SUNBEAM-ABC) to support the birth cohort study Systems Biology of Early Atopy (SUNBEAM). The center will assay biologic samples collected in SUNBEAM using omics and systems biology approaches to identify determinants of atopic disease, focusing on food allergy and atopic dermatitis (AD) in newborns, infants, and very young children. SUNBEAM-ABC will support the SUNBEAM birth cohort study by providing analytic infrastructure to 1) comprehensively understand molecular and cellular pathways that contribute to atopic disease development and 2) identify early predictive biomarkers.
Development of Microbiome-Related Approaches for Diagnosis/Mitigation/Treatment of Radiation Injuries (U01, Clinical Trial Not Allowed) RFA-AI-21-068: Released on September 20, 2021, the purpose of this funding opportunity is to 1) support research that will advance the understanding of how the microbiome affects radiation injury and 2) develop medical countermeasures that target the microbiome to prevent or mitigate radiation injury. It is anticipated that seven or eight awards will be made. Applications are due February 9, 2022.
Development of Radiation/Nuclear Medical Countermeasures (MCMs) and Biodosimetry Devices HHS-NIH-NIAID-BAA-75N93021R00019: (Presolicitation posted November 15, 2021) The goals of this contract solicitation are to support the research and development of biodosimetry approaches to assess and medical countermeasures to mitigate/treat acute and/or delayed radiation injuries.
Extended Longevity of 3D Tissues and Microphysiological Systems for Modeling of Acute and Chronic Exposures to Stressors. NNH21ZDA015N: NASA: This trans-agency announcement is directed by NASA and includes NIH (NIAID, NCI, NCATS), FDA, and BARDA. The contract solicitation seeks research on adapting existing 3D tissues and microphysiological systems (“organs-on-chips”) to extend the current longevity of 3D tissues and chips.
Notice of Special Interest (NOSI): Molecular and Genetic Characterization of Inborn Errors of Immunity NOT-AI-21-082: Published on December 1, 2021, the purpose of this NOSI is to 1) advance the experimental validation and functional characterization of genetic variants in coding or non-coding genomic regions that result in inborn errors of immunity/primary immunodeficiency diseases and 2) elucidate the molecular, cellular, and immunological mechanisms of these disorders. Understanding the genetic basis of primary immunodeficiency disorders is essential for their diagnosis, prognosis, and the development of precision therapeutics.
Notice of Special Interest (NOSI): Accelerating Progress in Celiac Disease Research NOT-AI-22-004: Published on November 23, 2021, the purpose of this NOSI is to inform potential applicants to NIH of special interest in research on the etiology and pathogenesis of celiac disease, identification of therapeutic targets, and development of preventative or disease ameliorating therapies/strategies.
Division Activities
Allergy, Asthma, and Airway Biology Branch
FARE Keynote: The NIAID Perspective. On October 19, 2021, scientific staff from the Allergy, Asthma, and Airway Biology Branch of DAIT/NIAID delivered a Keynote presentation at the Food Allergy Research and Education (FARE) 2021 Research Retreat. Following an introductory presentation on NIAID’s funding of food allergy research, a staff member discussed the NIAID food allergy prevention portfolio, while another member presented NIAID’s goals and activities on allergen immunotherapy in food allergy in the context of clinical and immunologic tolerance induction. The presentation was followed by a Q&A session.
2021 Annual Asthma and Allergic Disease Cooperative Research Center (AADCRC) Face to Face Meeting. On November 2 and 3, 2021, NIAID sponsored the 16th annual (virtual) meeting of the AADCRC investigators. The two-day meeting of PIs, co-investigators, students, and program staff included presentations from the 11 NIAID-funded research Centers and 4 NIAID-funded program project grant teams. There also was a special session featuring the work of AADCRC opportunity fund-supported young investigators.
Basic Immunology Branch
Immunity in the Elderly Annual Meeting. On September 28, 2021, the second annual meeting of the program to evaluate immune mechanisms in older adults was held virtually. The program is a partnership between NIAID and the National Institute of Aging and supports 11 projects from Stanford University, University of Washington, Western Michigan University, Dartmouth College, Vanderbilt University, Restorbio, Inc., Tufts University, Jackson Laboratory, University of Texas at Austin, and Yale University. Research progress and updates were presented. The meeting provided a venue for investigators to exchange ideas, foster collaborations, and leverage resources and expertise to advance the field.
Biological Functions of DEAD/H-box Helicases in Health and Diseases Workshop. On November 15 and 16, 2021, a workshop entitled “Biological Functions of DEAD/H box Helicases in Health and Diseases” was held virtually, organized by NIAID in partnership with the National Cancer Institute and the National Heart, Lung, and Blood Institute. The workshop, co-chaired by Dr. Michael Gale, Jr., and Dr. Ourania Andrisani, focused on recent advances in the roles of DEAD/H-box helicases in gene expression, cell development, cancer, infectious diseases, and immune system development and function. Speakers also discussed knowledge gaps, current challenges, and future research directions that may be pursued to expand our understanding of this important family of proteins and promote the utilization of the DEAD/H-box helicases as therapeutic targets.
Immune Mechanisms of Protection Against Mycobacterium tuberculosis Center (IMPAc-TB) Annual Meeting. On November 17 and 18, 2021, the second annual meeting of the IMPAc-TB contracts was held virtually. The overarching goal of the IMPAc-TB program is to identify and characterize immune responses required to protect a host from 1) initial Mycobacterium tuberculosis (Mtb) infection, 2) establishment of latent infection, or 3) progression to active tuberculosis (TB) disease. IMPAc-TB is the first NIAID trans-divisional program supporting studies to better understand TB immunology. The contractors are using murine, nonhuman primates, and human models; functional assays; and comprehensive immunologic approaches to help the broader TB vaccine community translate findings into improved vaccine strategies. Each of the principal investigators presented an overview of their programs, accomplishments achieved, and challenges encountered during the past year. They also provided updates about planned collaborations between the IMPAc-TB centers.
Immunity in Neonates and Infants Annual Meeting. On December 6 and 7, 2021, investigators awarded under the Immunity in Neonates and Infants program met virtually via Zoom for the final meeting of the program. Fifteen projects are supported under this program that is a partnership among NIAID, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Environmental Health Sciences. Investigators reported current progress on their projects that included data on infant immune regulatory mechanisms to allergens, commensal bacteria, vaccines, infections (including HIV), or environmental pollutants. Collaborations and discussions were continued to leverage resources and complementary expertise to advance the field.
Cooperative Center for Human Immunology (CCHI) Program. On December 9 and 10, 2021, the annual meeting was held virtually. The goal of this program is to support mechanistic and hypothesis-testing studies to understand human immune responses to infection, vaccination, and adjuvants, as well as immune-mediated diseases. Investigators from all eight centers presented their research progress, including recent updates on the COVID-19 studies supported by the supplement awards. Five awardees who received the CCHI Infrastructure and Opportunity Fund in 2021 also presented their work. In addition to the meeting, a virtual poster session was held for the week, providing an opportunity for trainees to showcase their research. Among them, seven of the posters were selected for short talks. The CCHI program is continuing to provide a platform for building collaborations, sharing the best practices, and leveraging resources among the groups.
Impact of Initial Influenza Exposure on Immunity in Infants Annual Meeting. On December 14, 2021, investigators and their teams awarded under this program met virtually. Two grants are supported under this program, which is a partnership between the Division of Microbiology and Infectious Diseases (DMID) and DAIT, NIAID. The grants are led by 1) Paul Thomas (St. Jude Children’s Hospital) and Aubree Gordon (University of Michigan) and 2) Mary Staat (Cincinnati Children’s Hospital Medical Center). The goal of this program is to establish, follow, and characterize longitudinal cohorts of infants to determine how initial and repeated natural influenza infections and/or influenza vaccinations shape infant and childhood immunity to future influenza exposures. Investigators presented recent updates and progress in each of their grants. The meeting encouraged investigators to exchange ideas and to foster collaborations across the program.
Transplantation Branch
Emerging Science and Technology in Transplantation (ESTT) Cooperative Group. On October 14, 2021, the final annual meeting of the first round of the ESTT cooperative agreement research program was held as a virtual meeting. Over the past five years, the ESTT has supported transplantation immunology research in three emerging areas of science and technology including intravital imaging, microbiota, and targeted therapeutic delivery. The program has fostered multi-disciplinary collaborations across the following fields: transplant surgery, immunology, biophysics, chemistry, computer sciences, live imaging, metabolism, and physiology. The Steering Committee meeting was attended by NIAID staff and representatives of the six U01 awardee institutions and the respective sub-awardees, including University of Pittsburgh, Brigham & Women’s Hospital, Yale University, Medical College of South Carolina, University of Missouri-Columbia, University of Chicago, and University of Minnesota. Principal investigators presented overall program achievements including new insights on immunological processes underlying graft survival and rejection, along with models and tools to facilitate research in all three priority areas.
Immunobiology of Xenotransplantation Cooperative Research Program (IXCRP) Annual Steering Committee Meeting. On November 5, 2021, the IXCRP Steering Committee meeting was held virtually. This program focuses on development and optimization of preclinical pig to nonhuman primate (NHP) models of islet, kidney, heart, and liver xenotransplantation. Attendees included the NIAID-funded investigators of five research sites, as well as investigators from the National Swine Research and Resource Center and the Southwest National Primate Research Center. During this interactive meeting, IXCRP investigators presented research progress made in the 2nd year of this funding cycle and discussed collaborations, reagent sharing, and resource availability. The investigators have overcome many obstacles to successful xenotransplantation with survival and function of pig kidney and heart xenotransplants in NHPs now extending up to 500 days and 6 months, respectively. These achievements are paving the way toward a xenotransplantation clinical trial. The hope is that xenotransplantation will provide a solution to the current shortage of human organs for transplantation and treatment of patients with end stage organ failure in the near future.
Nonhuman Primate Transplantation Tolerance Cooperative Study Group (NHPCSG). On November 30 and December 1, 2021, the annual NHPCSG steering committee meeting was held virtually. This multi-institute program supports two U01 and four U19 projects focused on evaluating novel and refining existing regimens for the induction and maintenance of transplant tolerance in nonhuman primate (NHP) models with accompanying mechanistic studies designed to elucidate the immunologic basis of tolerance and/or rejection. The meeting included U-award project presentations, updates on short-term Opportunities Pool funded projects, guest speakers, and presentations from key partner programs, including the NHP Reagent Resource and the NHP MHC and KIR Allele Discovery and Typing Technology Development contract. While common challenges and needs were discussed, consortium members repeatedly highlighted the importance of the NHP model in helping transition approaches for extending allograft survival and tolerance from preclinical studies to clinical trials in transplantation.
Clinical Trials in Organ Transplantation in Children and Adults (CTOT-CA). On October 15, 2021, the inaugural kick-off meeting of the newly awarded CTOT-CA was held virtually. CTOT-CA is a cooperative research consortium resulting from a merger of two longstanding Transplantation Branch initiatives, the Clinical Trials in Organ Transplantation (CTOT) and Clinical Trials in Organ Transplantation in Children (CTOT-C) consortia. The mission of the group continues to be to further our understanding of and ultimately reduce immune-mediated morbidity and mortality of allotransplantation. In addition, and in collaboration with NIAID’s DMID, this renewal includes an intensified focus on research into infectious illness in transplant recipients. The seven U01 awards were made to Massachusetts General Hospital, University of Pennsylvania, Boston Children’s Hospital, Northwestern University, University of Washington, and Duke University (2 awards). Each award represents a multi-site research team from institutions across the United States, each of which will be conducting a clinical trial of innovative interventions targeting graft rejection or infectious disease, accompanied by studies of immune mechanisms.
Immune Tolerance Network. Investigators at Duke University and the University of San Francisco are about to launch two clinical trials to test the use of innovative strategies to treat highly sensitized kidney transplant candidates. Approximately 12,000 of the 93,000 Americans currently listed for a kidney have high levels of antibodies against nearly all potential kidney donors. The difficulty of finding suitable donors for these individuals leads to long waiting times and high wait-list mortality (> 35 percent). Each of these strategies takes a unique approach to the removal of the antibody-producing cells prior to transplant in high risk/high reward pilot trials.
Autoimmunity and Mucosal Immunology Branch
Autoimmunity Centers of Excellence Steering Committee Meeting. On November 18 and 19, 2021, the Autoimmunity and Mucosal Immunology Branch (AMIB) hosted the fall virtual meeting of the Autoimmunity Centers of Excellence (ACE) Steering Committee. The main business was a review of the first two years of the Collaborative Projects: three groups focused on lymphocyte regulation, biomarker discovery, and immunity within peripheral tissues. Plans were discussed for continuation of the Projects through the final two years of this ACE program cycle. The investigators also heard from NIAID staff experts (Taunton Paine and Dawei Lin) about the new NIH data sharing policy that comes into effect January 2023. Principles and implementation were discussed. The ACE investigators also reviewed the status of three clinical projects they have initiated (NCT04918147, NCT05048238, one registration in process) with an additional project in late development, and COVID-19 projects assessing infection in children (NCT04588363) and vaccination responses in patients with autoimmune diseases (NCT05000216).
Radiation and Nuclear Countermeasures Program (RNCP)
NIAID/AFRRI Annual Meeting. On October 22, 2021, NIAID/RNCP held an annual meeting for the NIAID/AFRRI-USUHS Interagency Agreement (IAA) that was established in 2005. The meeting was attended by NIAID/DAIT and AFRRI/USUHS leadership and scientific staff. The IAA consists of five Work Plans that focus on small and large animal model development and testing of medical countermeasures to treat radiation-induced injuries. Scientific updates were provided by the Work Plan PIs with strategic discussion sessions to address identified challenges.
2021 Annual Update Meeting for the Centers for Medical Countermeasures against Radiation Consortium (CMCRC). On November 18 and 19, 2021, the CMCRC annual meeting was held virtually, marking the 2nd year of the 4th edition of the CMCRC. Currently awardees are the University of Maryland School of Medicine, Columbia University, and Duke University. Each of the centers provided an overview of the research they will pursue during this funding period. The meeting offered an opportunity to showcase the portfolio to other key stakeholders from partner federal government agencies (NCI, BARDA, NASA, DoD, and FDA). In addition, the meeting fostered dialog and collaboration among the CMCRC investigators and program staff regarding future research and development directions. Also present were four members of the External Advisory Board, who provided their insight and advice about the research discussed.
Cellular Therapies Portfolio Annual Meeting. On December 16, 2021, NIAID/RNCP hosted a virtual meeting for seven five-year, U01 awards made under RFA-AI-17-001. This funding supports studies to evaluate candidate cellular therapies to treat radiation-induced injuries in appropriate in vivo models. PIs presented updates on their studies, and the RNCP provided scientific guidance and resources to assist in moving cellular therapy products along the FDA Animal Rule licensure pathway to be considered for eventual licensure.
FY 2023 Research Concept Clearances Presented to Division Advisory Council
The subcommittee endorsed and unanimously approved the following research concept clearances:
NIAID Vaccine Adjuvant Development Program in Infectious and Immune-Mediated Diseases
The objective of this initiative is to support development of novel, promising vaccine adjuvants towards licensure for human use by establishing and expanding the availability of novel vaccine adjuvants that researchers can use for preclinical vaccine development and clinical evaluation in both infectious and immune-mediated diseases.
Presentation of Three SBIR Topics for the Omnibus 2023 SBIR BAA Solicitation
- Adjuvant Development for Vaccines for Infectious and Immune-Mediated Diseases
- Adjuvant Discovery for Vaccines for Infectious and Immune-Mediated Diseases
- Reagents for Immunologic Analysis of Non-Mammalian and Underrepresented Mammalian Models
V. Report of the Microbiology and Infectious Diseases Subcommittee–Emily Erbelding, M.D., M.P.H., director, DMID
Director’s Report
Dr. Emily Erbelding, director of the Division of Microbiology and Infectious Diseases (DMID), chaired the NIAID Microbiology and Infectious Diseases Council Subcommittee meeting on January 31, 2022. She provided a DMID personnel update, recognizing new staff appointments made in the Division since the last Council meeting, including Catherine Bigger, Office of Biodefense, Research Resources and Translational Research (OBRRTR); Olivia Sparer and Brenda Larkin, Office of Clinical Research Resources; and Krista Cato, Enteric and Sexually Transmitted Infections Branch. She also noted the recent departure of Dr. Alan Embry, chief of the Respiratory Diseases (RDB) Branch, who was also serving as the senior advisor for pandemic preparedness in the NIAID Office of the Director. Dr. Teresa Hauguel is currently serving as the acting chief of RDB.
Following staff introductions, Dr. Erbelding reported on several activities, including:
- Update on the NIH Trial to Evaluate Safety, Immunogenicity of Various Vaccine Booster Regimens – this study, known as the Mix and Match Trial, was designed to test safety and immune response of all possible combinations of licensed and authorized COVID vaccines when used as a prime with other authorized or licensed vaccines used as a boost. The data generated provided a basis for the recommendation by the Advisory Committee on Immunization Practices that different mRNA vaccine products could be used safely in prime-boost combinations.
- Influenza Surveillance – NIAID Centers of Excellence for Influenza Research and Response investigators have found that antibodies elicited by the 2021-2022 Northern Hemisphere influenza vaccine poorly neutralize a unique H3N2 clade circulating at elevated levels, indicating a possible antigenic mismatch for this year’s influenza season.
- First animal model qualified under FDA’s Drug Development Tools (DDT) Qualification program – DMID, working closely with FDA over the past 10 years, generated data that was used by the FDA to qualify the first animal model under the program, a model for testing therapeutics against tularemia.
- Public Health Service Commissioned Corps Awards – DMID staff members were recognized with the following awards: Cristina Cardemil received an Outstanding Service Medal for continuous outstanding leadership in global and domestic infectious disease prevention and control; Lori Newman received an award for participation on the NIH Opioid Overdose Response Team; and John Pesce received awards as part of the FDA Opioid Overdose Response and Naloxone Training Team and the PACE Opioid Plan Development Team.
- American College of Physicians Award – Dr. John Beigel, associate director for clinical research in DMID, received the Harriet P. Dustan award, which is bestowed for outstanding work in science as related to medicine that has been nationally or internationally recognized.
- Pandemic Preparedness – NIAID hosted a Workshop on Pandemic Preparedness: The Prototype Pathogen Approach to Accelerate Medical Countermeasures, which convened on November 8 and 9, 2021. The workshop introduced NIAID’s pandemic preparedness strategy, recapped NIAID’s previous experience applying the prototype pathogen approach to the COVID-19 response, and requested feedback from the scientific community on identifying and prioritizing prototype pathogens within viral families of highest pandemic potential for the development of medical countermeasures. Related to the workshop, Dr. Erbelding presented a new NIAID concept for fiscal year (FY) 2023 titled Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness (ReVAMPP) Centers, which would aim to advance scientific knowledge needed to develop vaccines and mAbs for prototype viral pathogens of virus families with pandemic potential. At present, specific funds have not yet been identified to support this program, but the Institute may receive funding specifically for pandemic preparedness, which would be used to establish this new program. Funds will not be diverted from the payline or other targeted programs to support the concept.
Finally, Dr. Erbelding presented three topics for inclusion in the 2023 Small Business Innovation Research (SBIR) Contract Solicitation for the Subcommittee’s consideration. All were approved by the Subcommittee:
- Adaptation of CRISPR-Based In Vitro Diagnostics for Rapid Detection of Select Eukaryotic Pathogens - To adapt CRISPR-based diagnostic technologies to detect select eukaryotic pathogens at the point of need with higher sensitivity and specificity than rapid diagnostic tests (RDTs) in current use.
- Modular Sample Preparation for In-Field Viral Discovery - To develop modular, rapid, and reliable sample processing technologies that can be used in combination with an established diagnostic platform (e.g., NGS, LFIA, LAMP) for the detection of viral pathogens with pandemic potential.
- Artificial Intelligence To Improve Clinical Microscopy for Diagnosis of Infectious Diseases - To develop artificial intelligence (AI) applications to improve clinical microscopy for diagnosis of infections, especially automated smear reading of blood, sputum, stool, or other clinical samples with the goal of improving current, widely used diagnostic tools.
In addition, Dr. Wilbert Van Panhuis, director of the NIAID Office of Data Science and Emerging Technologies (ODSET), presented two ODSET-led SBIR topics. Both were approved.
- Advanced and Immersive Visualization Tools for Infectious and Immune-Mediated Disease Research - To support the development, enhancement, or adaptation of immersive 3D visualization tools in combination with machine-learning algorithms to accelerate data analysis applicable to infectious and immune-mediated diseases.
- Data Science Tools for Infectious and Immune-Mediated Disease Research - To support the development or enhancement of computational tools, such as software, workflows, data models, database methods, etc., that can be readily used by researchers to find and use data more effectively for research on infectious and immune-mediated diseases.
FY 2023 Concepts Presented for Clearance
The following concepts were presented to the Subcommittee. All concepts were approved.
Understanding the Clinical History of Bacterial Sexually Transmitted Infections (STIs) To Accelerate Diagnostic and Vaccine Development – this concept would support studies that may lead to new and improved approaches to understanding the clinical history of gonorrhea, syphilis, and chlamydial infections. The Subcommittee members expressed strong support for the concept, noting the need for studies to better understand the human immune response after infection with bacterial STIs. Program acknowledged a recommendation by Subcommittee members to clearly define the types of studies to be supported in the concept, and eventual funding opportunity announcement, to reflect clinical history of infection versus natural history, which comprises infection through diagnosis, treatment, and follow-up. The Subcommittee unanimously approved the concept.
Understanding Persistent Signs and Symptoms Attributed to Post-Treatment Lyme Disease – this concept would support research that aims to better understand the persistent symptoms that are attributed to Lyme disease. The Subcommittee members expressed support for the concept, noting both its importance in addressing an understudied issue in Lyme disease and its potential to provide insight into other post-infectious clinical syndromes. The Subcommittee members provided additional insight into the clinical spectra associated with persistent Lyme symptoms and encouraged consideration of the microbiome and perspectives from long COVID studies in addition to the more established hypotheses associated with persistent infection, autoimmunity, coinfections, and chronic inflammatory responses. The Subcommittee members also stressed the importance of studies involving human subjects and/or human clinical samples rather than animal models, when possible, to ensure relevance to human disease. Finally, it was suggested that a funding opportunity announcement for this concept request that applicants provide evidence of direct relevance to known signs and symptoms of post-treatment Lyme disease, as opposed to general conjecture. The Subcommittee unanimously approved the concept.
Partnerships for the Development of Vaccines Against Select Bacterial Enteric Pathogens – this concept would help advance vaccine development for select NIAID high priority, Category B enteric pathogens that are recognized as Serious threats in the CDC's 2019 report “Antibiotic Resistance Threats in the United States”. The Subcommittee members voiced strong support for the concept. One Subcommittee member applauded NIAID’s persistence towards addressing a decades-long need to combat diseases caused by these pathogens, which have endured and troubled humans for a long time. Another Subcommittee member noted that this concept represented an exciting, worthwhile goal in an area for which further innovation is needed. One Subcommittee member advised Program to include new vaccine approaches (e.g., mRNA-based vaccine constructs) and strategies for vaccine improvement (e.g., innovative modifications to existing platforms). The Subcommittee unanimously approved the concept.
Partnerships for the Development of Novel Therapeutics To Combat Select Antibiotic-Resistant Bacteria and Fungi – this concept would support the development of novel therapeutics for select pathogens in which drug resistance poses a significant public health concern. The Subcommittee members fully supported the concept and appreciated the urgent need for the development of novel therapeutics to combat antibiotic resistance, a top threat to public health and a priority across the globe. The Subcommittee members agreed that the research to be supported through a resulting funding opportunity announcement may lead to next generation solutions for antibiotic resistance. The Subcommittee members suggested that program pay attention to the development of animal infection models in applications as they are very useful tools for antibiotic lead optimization and drug candidate advancement. The Subcommittee unanimously approved the concept.
Development and Optimization of Next-Generation Immunological Assays To Support Influenza Clinical Studies and Trials – this phased concept would support activities including but not limited to optimization of sample collection procedures (e.g., mucosal, lymph node, and bone marrow sampling) and identification of assay and platform parameters. The Subcommittee members expressed strong support for the concept, noting that improved immunological assays have been a longstanding need for the influenza research community. The Subcommittee members noted that the field relies heavily on classical immunological assays and the established correlates of protection, and that there is a need to develop assays that measure immune correlates other than antibodies to influenza hemagglutinin. The Subcommittee members recommended that the field develop high-throughput assays that can be used more widely. The Subcommittee members noted that in the future there will be more interest in vaccination strategies that utilize neuraminidase antigens, and that next-generation immunological assays should include assays to assess immune responses to neuraminidase, beyond the classical and low-throughput neuraminidase inhibition assays. The Subcommittee unanimously approved the concept.
VI. Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)–Carl Dieffenbach, Ph.D., director, DAIDS
Attendance
Members: Kenneth A. Freedberg (Chair), Elaine J. Abrams, Richard T. D’Aquila, Ian Frank, Reuben S. Harris, Stephaun E. Wallace. NIAID Advisory Council Liaisons: Ritu Agarwal, Monica Gandhi, Paul Goepfert, Amita Gupta, Keith R. Jerome, Audrey Pettifor. Participating Non-voting Ex-officio Members: Melissa Turner, Demetre Daskalakis, Maureen Goodenow. Office of AIDS Research Advisory Council (OARAC) Liaison: Tricia H. Burdo.
DAIDS Representatives: Carl Dieffenbach, Sarah Read, Diana Finzi, Peter Kim, Mary Marovich, Manizhe Payton, Carol Worrell, Sheryl Zwerski. Executive Secretary: Pam Gilden.
Welcome and Approval of Minutes
Kenneth A. Freedberg, M.D., M.Sc. (Chair)
Dr. Freedberg welcomed everyone and the ARAC members unanimously approved the minutes of the September 13, 2021 meeting.
Director’s Report and SBIR Contract Topics
Carl Dieffenbach, Ph.D.
Dr. Dieffenbach welcomed a new member to the ARAC and NIAID Advisory Council: Keith R. Jerome M.D., Ph.D. Fatima Jones, Ph.D., was introduced as the newly appointed chief of the Drug Development and Clinical Sciences Branch in the DAIDS Therapeutics Research Program.
Budget Update
For FY 2022, the Institute is operating under a continuing resolution (CR) until the House and Senate reach an agreement and pass a budget. An additional COVID-19 supplemental package is being negotiated.
NIAID/DAIDS FY 2020 and FY 2021 Report Card
Tables summarizing the NIAID paylines and success rates for the last five years were presented.
Key points:
- The NIAID paylines were steady at 14th percentile, and 18th percentile for new PIs.
- NIAID AIDS success rates were relatively steady for R01s, R21s, and P01s.
- Comparative success rates of NIH, NIAID, and AIDS RPGs – AIDS RPGs similar to that for NIH in FY 2020 and FY 2021 and better than NIAID overall in FY 2020 and FY 2021.
Discussion:
Q: It’s encouraging to see that paylines have held steady. I'm wondering about the diversity metrics of gender, race, and ethnicity.
A: In general, we are seeing a fairly consistent response across gender. Race is fairly hard to sort out. There is a challenge to identifying those who don’t participate in reporting. We are very committed to diversity and inclusion and equity; it remains a high priority for the Division and for the Institute.
Q: While we've seen the interim paylines for R01s and others, there's no interim payline for K awards. Do you anticipate making decisions before late February (when current CR ends) or will that just wait for the full budget for Ks?
A: The decisions on Ks will be made when there is a full budget.
Q: Are the number of ESI applications declining due to COVID? There is some concern that young investigators, especially virologists, have been leaving academia and going to work at companies.
A: Numbers shown are not broken down by early stage or late stage. NIH has also experienced staff departing the federal workforce to work at private sector companies.
Q: In addition to the RPGs, is there any information on K applicant numbers?
A: No information yet for the K applicants.
Q: Are there any brainstorming ideas to start an initiative to ‘build back better’ the next generation of investigators to help ESIs recover from the pandemic, and to encourage ESIs to apply for grant funding?
A: Currently we are struggling to balance ESI with diversity candidates and there is an emphasis for diversity and inclusion at this point. Ideally, we would like to address all groups.
Q/Comment: Following on from previous comments, this is a crucial issue that involves recruitment challenges. Hopefully we can find ways to incentivize with new programs, new funding streams, or supplements to retain ESIs in academia and applying for grants.
A: AIDS is unique because we control our budget with OAR. Getting other NIH Councils involved in this matter would be important. Committee members should consider writing to Dr. Maureen Goodenow at the NIH Office of AIDS Research (OAR) about this issue.
Q: I know there's a delay in getting data for us to review. Is there a solution to where we can get greater granularity, more real-time data or updated data?
A: It takes a long time to get data cleaned and finalized at the end of a fiscal year. This is the reality and the challenge we face.
Comment: The OAR has been working on the ESI issue across NIH and established a special task force to address HIV early-career investigators. It might be beneficial to receive an update on the progress. Links to further information on the OAR website: https://oar.nih.gov/about/directors-corner/enhancing-support-next-generation-hiv-researchers and https://www.oar.nih.gov/trans-nih-hiv-research-program/hiv-early-career-resources.
A: We will follow up for a future meeting.
Scientific and Programmatic Updates
Long-Acting Injectable Cabotegravir Studies
Licenses have now been obtained for long-acting cabotegravir based on results from the HPTN 083 and HPTN 084 trials. The FDA announced the decision on December 20, 2021, amidst ongoing COVID news.
The HPTN 083-01 and 084-01 studies are ongoing to ensure access to cabotegravir for adolescents.
Other important large ongoing trials were briefly reviewed:
- A5300B/PHOENIx
- A5332 REPRIEVE
- MTN 042
- MOSAICO/HVTN 706
Accelerating COVID Therapeutic Interventions and Vaccines (ACTIV)
ACTIV-2 (NIAID) continues to be a workhorse for outpatient studies and other trials will shortly open.
SARS-CoV-2 Antibody Landscape (in process)
The current status of several antibodies in development were summarized. EUAs are available for several monoclonal antibodies (mAb) despite the Lilly combination and the Regeneron combination which have been eliminated due to the Omicron variant. Omicron-specific but broad mAbs are being developed by these companies in order to seek EUA reissues.
Efficacy Testing of COVID-19 Vaccine Candidates
These vaccines and studies were summarized. Data supporting another boost continues to grow. Dr. Fauci had stated the need to plan for the next generation of vaccines. These would ideally induce mucosal immunity and the type of immunity initiated by mRNA vaccines. A research plan is currently being developed to achieve this goal.
SBIR Contract Topics
PHS 2023-1 Solicitation for NIH and CDC SBIR Contract Proposals – DAIDS Topics
One new SBIR contract topic and two for reissue were described. The two topics for reissue that were previously approved by ARAC: (i) Point-of-Care HIV Viral Load and Drug Adherence Assays To Accelerate “Ending the HIV Epidemic (EHE)”, and (ii) Development of Assays To Differentiate HIV Infection From Seropositivity Induced by HIV Vaccines.
The new topic was summarized:
Development of a Simian Immunodeficiency Virus (SIV) and Simian Human Immunodeficiency Virus (SHIV) Database.
The objective of this topic is to develop a database that categorizes SIV and SHIV strains in a searchable way. Eventually, this database should be integrated into another larger NIH-supported database. Phase I and II activities include: establish a project team to define the critical data to be collected, develop this into a software package, and also to develop the tools and technologies required to obtain and curate data. This will be tied to the HIV Reagent Program with the ability to have strains and appropriate reagents to help bring a level of quality control to the field. Ultimately a website will be created for user access, end use, and to continue to curate literature.
Comment: Glad to see this information. This new topic will provide a valuable resource to the field.
Office of AIDS Research Advisory Council (OARAC) Update
Tricia H. Burdo, Ph.D.
Highlights of the 58th OARAC meeting held on October 28, 2021, were presented.
OAR Director’s Report
This featured a report from the OAR Director Dr. Maureen Goodenow, updates from the HIV ARV and OI Guidelines Working Groups, a presentation from the CDC Director, and an update from the Director of the White House Office of National AIDS Policy.
Strategic Engagements
The OAR Director’s Report included information on the 48 listening sessions held since 2018—a summary report is being prepared for the OAR website; NIH EHE activities in FY 2019 developed by the NIH HIV/AIDS Executive Committee; strategic engagements with Congress, the White House, HHS and others; NIH representation on PACHA, and on the NHAS Steering Committee.
Priorities and Scientific Advances
The FY 2022 NIH AIDS Professional Judgment Budget report is available on the OAR website for review.
OARAC Member updates
Two new OARAC ad hoc members were introduced: Dr. Shruti Mehta from John Hopkins School of Public Health, and Dr. Ivy Turnbull of the AIDS Alliance for Women, Infant, Children, Youth and Families.
HIV Antiretroviral and OI Guidelines Working Groups of OARAC
Report-outs on: Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV; and Prevention and Treatment of Opportunistic Infections in HIV Exposed and HIV-Infected Children.
CDC Update on Ending the HIV Epidemic (EHE)
CDC Director Dr. Rochelle Walensky outlined the CDC's role in the Ending the HIV Epidemic Initiative and presented examples on how the CDC plans to address each of the EHE pillars--to diagnose, treat, prevent, and respond.
White House Office of National AIDS Policy Update
Mr. Harold Phillips, director of the White House Office of National AIDS Policy, discussed the Biden Administration's support of EHE initiatives and HIV-related priorities, updates to the National HIV/AIDS Strategy, and interagency collaborations.
All OARAC meetings are archived on the NIH Videocast website under Past Meetings.
Next OARAC meeting: February 24, 2022 (Virtual).
Discussion: None.
NIAID/DAIDS Programmatic Overview: Key Accomplishments and Future Directions
Basic Sciences Program
Diana Finzi, Ph.D.
Outline for the Basic Sciences Program (BSP):
- Overview of the Basic Sciences Program
- Impact of SARS-CoV-2
- HIV Highlights
- Future Directions
Below are the key points from the presentation:
Overview of BSP
BSP mostly supports early-stage science, specifically the early indications of what might eventually lead to important breakthroughs. The foundations are in our large number of unsolicited grants, but BSP also solicits grants in order to indicate direction and areas of particular need. BSP collaborates with other DAIDS Programs (Therapeutics, Prevention and Vaccines) and we often see our early work bear fruit in those areas.
The primary area of focus in the basic sciences is our mechanistic work with particular attention to latency versus cure. In targeted interventions, we have an increased focus on non-traditional therapeutics, such as gene-and cell-based therapies, biologics, and RNA therapeutics, but we also continue to work on specific interventions to validate HIV targets and small molecule inhibitors.
In epidemiology, we have maintained work on clinical outcomes of HIV through very large cohorts throughout the world and our electronic health records research, recently focusing more on tuberculosis (TB) and the intersection of TB and HIV. For the Ending the HIV Epidemic (EHE) initiative, BSP has focused on collaboration and alignment between federal agencies to fund implementation research.
Impact of SARS-CoV-2
Work for periods of this last year has periodically shifted to COVID. Examples of contributions included the following:
- Helped to move protocols along at the NIAID VRC
- Helped to create a number of new proposals to the emergency Rapid Acceleration of Diagnostics Programs: RADx-Tech, RADx-rad, RADx-UP
- Helped to review emergency NOSIs, emergency FOAs, supplement requests, ranging in topics from diagnostics to therapeutics, to basic epidemiology, to long-term outcomes
- Reviewed proposals from thousands of investigators submitted to NIH and other agencies, such as BARDA.
Highlights
Three examples of the benefits of sustained support from BSP were discussed:
HIV Reagent Program
The reagent program develops and produces state-of-the-art reagents and then provides those at no charge to qualified investigators throughout the entire world. The program has served as an example and seed for other repositories. For drug repurposing, there is a ready stock of HIV drugs that are immediately available upon request to send to coronavirus labs for testing. A new award has just been made to the ATCC that will help maintain this stock of useful, quality-controlled, and up-to-date reagents.
CFARs
Supporting CFARs across the United States in HIV research has been critical in jumpstarting the EHE initiative and informing HHS and partners on evidence-based practices.
Basic R01-type studies
mRNA studies, that represents one example of BSP supported research, was briefly summarized. This covered its therapeutic timeline since its initial discovery in 1961, and the challenge of the immune system to using engineered RNA to instruct cells to make specific therapeutic proteins. This problem was resolved by a grantee in 2006 and this work has led to technologies now being used to effectively combat the COVID pandemic.
Anticipated Priorities
These grant funding opportunities currently under development were covered:
- Molecular dynamics of HIV
- Enhancing HIV reservoir susceptibility to death
- Optimizing the anti-HIV CD8+ T-cell response to achieve an HIV cure
- LITE (Limited Interaction Targeted Epidemiology)
- A behavioral epidemiologic study in J. AIDS authored by Denis Nash and Christian Grov et al. showed that persistent methamphetamine users had seven-fold increased risk of acquiring HIV; also, black MSM had three-fold increased risk of HIV as compared to white MSM.
Future Directions
Summaries of future directions for the following BSP programs were covered in the presentation:
- Structural Biology Centers
- Martin Delaney Collaboratories
- Epidemiology: EHE; AWARE; IeDEA consortium
Discussion:
Q: Follow-up question about the study on methamphetamine use and its role in sero-conversion—we don’t really have any sort of interventions for people who are on methamphetamines. It's something that we're talking about at CDC. Is there any sort of awareness that you have in terms of next steps?
A1: DAIDS is partnering with our colleagues in NIDA who seem to be very interested in these findings.
A2: This morning’s NIAID Council remarks from Dr. Fauci about the NIH FY 2022 budgets highlighted NIDA's large budget increase to target methamphetamine use. While this is recognized as a significant problem, NIDA’s progress working on it has been difficult. DAIDS will continue its collaboration with NIDA on this matter.
Q: There are behavioral factors underlying why there's this increased HIV risk with methamphetamine use, but could there also be some biology underlying it?
A: NIDA has a lot of programs on that, in terms of changing receptor densities and things like that. The particular study on methamphetamine use discussed here was tied to behavior.
Q: Are the LITE treatment grants that we talked about last time at ARAC going to be launched soon because they are so important in trying to get at that last 10 percent of non-virologically suppressed through the creative social media approach?
A: We are working on this and will report results at a future meeting.
Q: Regarding the IeDEA consortium, will there be additional biospecimen collection in a repository? This would require significant resources but is a much-needed global resource.
A: We have talked about this in DAIDS and the high cost has been prohibitive. Also, trusting the quality of the specimens is a consideration, and finding a way to do this in a cost-effective manner is certainly a challenge. Strategic collection would be an approach.
Vaccine Research Program
Mary Marovich, M.D.
This overall programmatic update for the Vaccine Research Program (VRP) covered:
- VRP Mission
- Leveraging HIV Vaccine Research and Development for the Strategic U.S. Government COVID-19 Response
- HIV-1 Vaccine Discovery and Design Advances
- Vaccine Concepts in Advanced Clinical Testing
- Future Directions for Vaccines
Below is a summary of the key points:
Update: Efficacy Testing of COVID-19 Vaccine Candidates
- The contribution that the HIV/AIDS field has made to the successes within the COVID field, particularly the vaccine landscape, cannot be over-emphasized. The mRNA platform was used for expediency, and Moderna was just issued its license today from the FDA.
- A high-level summary of Phase 3 COVID-19 vaccine candidates and associated studies were presented. This included Moderna’s mRNA platform, AstraZeneca’s adenoviral vector platform, and the trimeric protein platforms of Novavax and Sanofi.
- SARS-CoV-2 mAb prevention portfolio and prevention trials currently being implemented were discussed.
VRP Mission: Develop a safe and effective HIV vaccine to control and end the HIV epidemic.
Leveraging the HIV Vaccine Enterprise for the U.S. Government COVID-19 Response
Workshop takeaways
- A workshop was held in October where the lessons learned are to be examined and where the HIV vaccine enterprise was leveraged to contribute to COVID vaccine development.
HIV Vaccine Discovery and Design Advances
NIH HIV Vaccine Strategies: Moving Forward
- This involves two approaches:
- Empirical (RV144 trial). Vaccines to improve potency, durability of non-neutralizing anti-Env V2 antibodies.
- Theoretical broadly neutralizing antibodies (bNAbs). Vaccines that induce bNAbs and immunoprophylaxis with bNAbs.
- This presentation focused on the theoretical approach which would develop vaccines that could induce neutralizing antibodies with PrEP and then use them in a test of concept to determine if these neutralizing antibodies could prevent acquisition of HIV. This was the AMP study in which results came out last year.
- The process of inducing bNAbs through vaccination was described. Targets to the HIV envelope are essential for this approach and several which are susceptible to neutralization have been identified.
- Naïve B-cells are primed with the chosen immunogen to ideally trigger the broadest response. These primed cells would now have to stay within the germinal center and undergo multiple rounds of affinity maturation and they also need to undergo somatic hypermutation, T-follicular help, sequential immunization and boosting. There is growing confidence that this will result in mature B-cells that can produce broadly neutralizing antibodies.
- Reported advances in this area:
- CRISPR technology in a mouse model to develop customized humanized knock-in B-cell receptor-expressing naïve precursors all within a few weeks.
- The IAVI G001, Phase I trial using an eOD-GT8 60mer that is adjuvanted with AS01B. This immunogen was shown to activate precursor pools of VRC01-class IgG-positive B cells.
- Recapitulation of HIV-Env co-evolution in NHP was shown to lead to Ab neutralization breadth. This model could be very helpful and informative for bNAb development for humans. Germinal cell approaches were also described as useful for potentially developing a broad B-cell repertoire.
- An SMNP adjuvant, comprised of Saponin and the TLR4 agonist MPLA into nanoparticles, were shown to induce superior Ab and germinal center responses.
- Examples of vaccines being translated from NHP to humans were discussed and covered the BG505 SOSIP immunogen studies in the recent HVTN137 clinical trial.
- The VRP HIV Env nanoparticle/mRNA portfolio as well as plans to address the need for adjuvants was briefly summarized.
Vaccine Concepts in Advanced Clinical Testing
- “The search for an HIV vaccine, the journey continues” paper authored by Carl Dieffenbach and Anthony Fauci was briefly overviewed which covered goals for continued HIV vaccine development, discovery design, and the need to foster multi-sector partnerships, and test various vaccine concepts.
- Key lessons and next steps from the published AMP study were reviewed which showed that if the virus was susceptible to the VRC-01 bNAb, they were able to prevent acquisition.
Future Directions for Vaccines
- The Collaborative HIV Immunogen Project (CHIP) was discussed which has the goal of coordinating immunogen development.
- Summary slides were presented of some immunogens for germline targeting and bNAb development, trimers to be used once primed, and protocols in the pipeline.
Discussion:
Q: Is there any early indication of which animal model might be best to mimic this sort of ongoing affinity maturation that's happening in humans, rare humans that actually develop broadly neutralizing antibodies?
A: The mouse models have been amazing because you can do experiments very quickly in them and they are inexpensive. You can make them in a couple weeks, they can be really customized to what you're looking at and the type of BRC or various others. Previously, the mouse model was never really a big saver in the HIV vaccine field, but with the latest improvements, including genetic technology it's so much faster. We do like the primate model for some of the other attributes: the ability to challenge and the fact that they do actually generate broadly neutralizing antibodies. There are a smaller percentage of animals, but I think the mouse model would probably be the biggest advance.
Q: The humanization of the model is a pretty important step forward, but there's some differences in the actual activation-induced action that drives the antibody process that could determine the repertoire.
A: I totally agree. The mice only live approximately two years and we're talking about compressing that. Some of the things that we've seen in the mouse model have really begun to come forward in humans.
Q: Can you expand a little bit on whether there are formal efforts to think about leveraging this huge investment we've made over the past two years for things like HIV and longer-term problems.
A: For example, regarding the AMP Study, we over-estimated the sensitivity of the circulating strains, in the area where we studied and I think that with the capacity that you're talking about, we probably could be much better informed about the evolution of the HIV epidemic which has really changed given the fact of the type of virus it is and all the other conditions, the ongoing other epidemics. So, I think that those technologies would be well-suited for the HIV vaccine or HIV research in general and I think we're really supportive and grateful that you have built that out.
Therapeutics Research Program
Peter S. Kim, M.D.
The mission of the DAIDS Therapeutics Research Program (TRP) was stated: to improve the health of people living with HIV (PLWH) by developing new and improved therapeutics and diagnostics and advancing associated strategies to achieve durable viral suppression and also ART-free remission; and to address co-infections and comorbidities with greatest impact on the health of PLWH.
Activities for the TRP are generally weighted towards clinical trials and comprises over 80 active trials or trials in development. A range of contractual resources are maintained to support these high-quality clinical trials and also maintains resources to support the discovery and preclinical development of new therapeutics.
Recent Advances, Ongoing Activities, and Anticipated Priorities
Four of the main therapeutic areas of interest were described in the presentation in more detail:
i. HIV and HIV-Associated Comorbidities
ii. Tuberculosis (TB)
iii. Hepatitis
iv. SARS-CoV-2/COVID-19
HIV and HIV-Associated Comorbidities
The portfolio in this area covers a range of preclinical and clinical studies focused on developing new technologies to improve care. This includes point-of-care and self-testing diagnostics, long-acting treatments that have the potential to attain the ultimate goal to improve outcomes, to empower people living with HIV and also to simplify care strategies domestically and worldwide. Key points summarized from this area included:
- STP0404 adjuvant. Highly potent first in class allosteric integrase inhibitor (ALLINI)
- Non-invasive plasma glycomic and metabolic biomarkers which may predict post-treatment control of HIV
- Discovered ability of HIV ability to evolve resistance against innate IFN responses
- Collaboration with NHLBI on large clinical REPRIEVE trial in PLWH. Correlation of plaques with increased risk?
- A5386: Clinical trial of the safety, tolerability, and efficacy of IL-15 Superagonist (N-803) with and without combination bNAbs to induce HIV-1 control during ATI
- bNAb-inducing vaccines may have therapeutic benefit for PLWH
- A5391: Doravirine for persons with excessive weight gain on Integrase Inhibitors and Tenofovir Alafenamide (The Do IT Study)
- Partnering with ACTG on new, small clinical trials unit to rapidly advance promising candidates into early phase and mechanistic clinical trials
- Multidisciplinary Treatment Approaches to EHE (RFA-AI-21-024): this FOA is for implementation research
- Accelerating research to improve patient care using the SBIR mechanism
- Partnerships with other ICs and the NIH Office of AIDS Research to advance research on HIV-related comorbidities
Tuberculosis and HIV
Long-term goals: enable new prevention strategies; develop and test new diagnostics and treatments for HIV/TB; advance TB vaccine science; and advance clinical/observational research in regions that are most affected by TB/HIV.
Key points summarized from this area included:
- Advances in the TB drug pipeline that offer new opportunities to improve treatment outcomes for PLWH.
- QT effects of bedaquiline, delamanid, or both in patients with rifampicin-resistant TB in a Phase 2 trial. These treatments were found to be safe.
- Collaboration with ACTG to develop a Phase II adaptive platform trial that could test a large number of potential combination regimens in parallel with the idea that dose regimens that have the greatest efficacy on liquid culture endpoints could then be moved into Phase IIC or Phase III clinical trials.
Hepatitis
Long-term goals: novel treatments for hepatitis B cure; improved preventive hepatitis B vaccine for PLWH; hepatitis C treatment simplification, including long-acting regimens and improved diagnostics for hepatitis C.
Key points summarized from this area included:
- A5379: B-enhancement of HBV vaccination in Persons Living with HIV (Bee-HIVe): Evaluation of
HEPLISAV-B
This Phase III/IV study will test a new hepatitis B vaccine (HEPLISAV-B) with objectives that include comparing the seroprotective response (SPR) of a two-dose regimen of HEPLISAV-B versus a standard three-dose regimen of ENGERIX-B in HBV vaccine-experienced PLWH; and comparing the SPR of a three-dose regimen of HEPLISAV-B versus a standard three-dose regimen of ENGERIX-B in HBV vaccine-experienced PLWH.
SARS-CoV-2/COVID-19
This program in collaboration with the ACTG has been developing novel treatments for early COVID-19. What started out as one single study, called ACTIV-2, now has grown to a family of studies that we call ACTIV-2X, a group of studies designed to evaluate multiple antiviral treatments for early COVID-19 (Phase II through Phase III), that go by the names ACTIV-2, ACTIV-2B, ACTIV-2C, ACTIV-2D. More than 10 agents in the Phase II study category have been evaluated, and some of them have progressed into Phase III.
Discussion: None.
Prevention Sciences Program
Sheryl Zwerski, DNP, CRNP
The Prevention Sciences Program (PSP) overview covered:
- Background
- Program Orientation
- 2021 Accomplishment Highlights
- What is next?
- Challenges and Opportunities
Background
Data was presented showing the global number of PLWH, including those newly infected and the number of children, together with the number of AIDS-related deaths, the 2000-2020 global number of new infections and global distribution of new HIV infections by population for 2020.
The key points from the remainder of this presentation:
Program Orientation
PSP is comprised of four branches: Preclinical Microbicide and Prevention Research Branch, Clinical Microbicide Research Branch, Clinical Prevention Research Branch, and the Maternal, Adolescent & Pediatric Research Branch.
- High-level priorities of the PSP program: development of HIV prevention products; improve understanding of the biology of HIV susceptibility; improve engagement of key populations; improve HIV treatment and prevention in pregnant women and children; optimize strategies to diagnose, treat and prevent TB in the maternal and pediatric populations; and continue to evolve the cure research in infants and children.
PSP’s HIV Clinical Trials Networks: HIV Prevention Trials Network (HPTN) and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network. The Microbicide Trials Network (MTN) has moved into the HPTN in December 2021.
The Comprehensive Resources for Topical Microbicides and Biomedical Prevention contract, otherwise known as CRMP, is the foundation across the spectrum of PSP research. The CRMP contract will be renewing in FY 2023 with a new name, Resources to Advance Pediatrics and HIV Prevention Science (RAPPS).
2021 Accomplishment Highlights
Development of HIV Prevention Products
- FDA approval of CAB-LA for PrEP in individuals 35kg and above based on HPTN 083 & HPTN 084 studies
- Ongoing safety and pharmacokinetics trials of HIV monoclonal antibody combinations (HVTN 136/HPTN 092, HVTN 140/HPTN 101) done in collaboration with VRP
- Completed follow-up in MTN 034 (dapivirine ring and oral PrEP in African adolescents and young women) showed adherence was higher than previously observed for both products
- MTN 036 (two dosages of 90-day dapivirine rings [100 and 200 mg] compared to the 28-day ring [25 mg]) showed all three rings were well tolerated and the 90-day rings achieved higher dapivirine concentrations
Improve Prevention and Treatment for Pregnant Women and Children
- Organized a PREP in pregnancy workshop and participated in WHO/IMPAACT Call to Action for accelerating inclusion of pregnant women in ARV studies
- IMPAACT Study P1108 for children - the PK data resulted in a WHO rapid communication on Bedaquiline usage in young children for MDR TB
- Collaborated with BSP to launch a new pediatric Martin Delaney Collaboratory (MDC) called PAVE (Pediatric Adolescent Virus Elimination)
- Results from Cohort I of MTN 042 (dapivirine ring and oral PrEP in African pregnant women term gestations) showed adverse pregnancy outcomes and complications were uncommon when the DVR and TDF/FTC were used in late pregnancy; Cohort II is in progress
What is next?
Challenges for Future of HIV Prevention Research
- Bridging the gaps to advance promising next-generation non-vaccine HIV prevention products into human clinical testing.
- Focus on how to increase choice across populations who are in need of HIV prevention products in a way that is feasible and timely.
- Expanding the ethnographic studies to better understand desire and choice, and how to best engage key populations in HIV prevention and fill early prevention gaps.
Opportunities: HPTN Specific Aims
- These cover novel ARV-based HIV prevention methods and delivery systems, multipurpose prevention technologies, and integrated biomedical and socio-behavioral prevention strategies.
Challenges for Future Maternal/Child Research
- Optimizing maternal and child ART and TB regimens, and improving child friendly formulations
- Including pregnant and lactating women in studies earlier in product development is paramount and now further endorsed by PRGLAC & WHO
- Including adolescents and children earlier in product development and being sensitive to their needs in planning trial logistics
- Progress towards HIV-free remission in youngest populations
PSP COVID Work
- Expansion of the Emergency Use Authorization (EUA) for the Regeneron monoclonal antibodies to include post-exposure prophylaxis based on CoVPN 3502/REGN 2069
- Enrollment was completed for IMPAACT I-2032, the Remdesivir PK and safety study in pregnant women; results will be available soon
Discussion:
Comment/Q1: It was exciting to hear about adolescents and what we used to call combination prevention fitting into the agenda. In Sub-Saharan Africa, with IPM withdrawing the dapivirine ring application, how do you envision that playing out? How does that fit with NIH being part of the funding mechanism?
A1: NIH is very much committed to completing these bridging studies which will be required to move it forward. The ring received EMA approval and then WHO prequalification which has been very positive. We won't try and speak for IPM, except that they are the regulatory sponsors for the work. IPM is very committed, as are we, to make sure that there's choice for those populations and particularly in Sub-Saharan Africa where much more choice is needed. We really need to get every available possibility out there. They have filed and/or are planning on filing in various countries in Sub-Saharan Africa and our understanding is they expect to see those through. It remains to be seen exactly how those discussions will go, but we are very hopeful because of the EMA approval and the WHO prequalification that they'll be able to move forward.
Q2: For the contract ethnographic work, have grant RFAs been discussed in that area?
A2: To get things going the contract was an efficient way to move the ethnographic work forward as quickly as possible. We are taking what has been learned and making sure that we disseminate that both to the scientific community and to implementers. In terms of next steps, we will conduct further discussions and potentially a workshop will be considered; more to come on that.
Comment: Importance of community engagement. Considering the complicated nature of clinical trials and with the ongoing discussions about how trials will be designed going forward, I just wanted to communicate here that it's really important that communities are engaged in these conversations meaningfully so that people can understand what's happening, what's taking place, and that they are apprised of how things are moving forward.
A: Thank you so much. We couldn't agree more, and that's always been the case. We've certainly seen that over the past couple of years that this issue has become even more important and we are very much committed.
Office of Clinical Site Oversight (OCSO)
Manizhe Payton, M.P.H.
The mission of OCSO is to facilitate clinical research of the scientific programs of the DAIDS through oversight of clinical site capabilities and overall site performance by working with each of the four scientific programs at DAIDS: VRP, BSP, TRP and BSP, as well as with colleagues in the DAIDS Office for Policy in Clinical Research Operations (OPCRO). The OCSO mission is accomplished in the context of the scientific and programmatic priorities of the DAIDS programs and Network Leadership Groups.
The organizational chart for OCSO was summarized with brief descriptions of the roles of each of the four branches: Asia & the Americas Branch, Africa & the Domestic Partners Branch, Monitoring & Operations Branch, and Pharmaceutical Affairs Branch (PAB). The core business of OCSO provides monitoring and site oversight for a portfolio of over 200 clinical research sites worldwide, under the NIAID Clinical Site Monitoring contract, to fulfill the regulatory responsibility as a sponsor and assure participants’ safety as well as data quality. Onsite monitoring is outsourced to a contractor, PPD. Currently, OCSO is monitoring >90 clinical trials. OCSO also provides regulatory site inspection preparedness and support.
The PAB provides study product expertise including distribution and management of study product to clinical research sites at 27 countries worldwide under the NIAID Clinical Research Products Management Center contract with Thermo Fisher.
OCSO organizational priorities were outlined: Implement Remote Approaches to Site Oversight, Facilitate NIAID’s COVID Research Priorities, and Optimize Support of Clinical Research Sites. These have been reassessed considering the pandemic and are continually being evaluated to ensure they remain relevant and practical for these times. The approach includes a remote monitoring model, virtual interactive training and support for virtual site visits. OCSO has been involved in advancing NIAID’s COVID research agenda and specifically is integrally involved in the ACTIV-2 project driving site activities, monitoring and study product distribution/management for this COVID treatment protocol.
Going forward, the plan will be to use lessons learned over the past few years to evolve processes to support the changing landscape. OCSO continues to systematically evaluate existing processes around establishment of sites, new locations where research is conducted, monitoring activities, and pharmacy support. OCSO engages with stakeholders, listens and analyzes their feedback to inform refinements to our processes. We hear their concerns and challenges and strive to be transparent and practical in approaches to fulfill our regulatory responsibilities. OCSO works with stakeholders, both internally and externally, to prioritize implementation of initiatives to facilitate DAIDS scientific priorities.
Discussion:
Q: What do you see as major gaps helping you fulfill the mission of optimizing operations and using digital platforms to have real-time dashboards to collect data that can help see how quality is going, and how well the trials are being managed?
A: In this kind of environment we rely on technology to be able to give us more insight about the quality of data, and the progress of our trials. One important initiative that we're moving forward with is the centralized monitoring initiative where we'll be able to apply statistical methodologies to data quality, to be able to assess the quality of data and identify trends that remove our requirement to be onsite or to perform some of the traditional onsite monitoring.
Other initiatives in terms of remote activities that can be participant-based- electronic informed consent to help facilitate the research, advancement of some of the analytics that might be available to us to be able to trend progress, ability to look at portfolios and capacity at sites. That has really been challenging for us to be predictive about capacity and what the drivers of capacity are for sites, but we're still trying to obtain some of the characteristics of sites in order to see if there's any way we can gather any information about what some of the key drivers might be.
We have been tremendously impressed by the dedication, the perseverance, and the innovation of the sites to be able to continue operations to the best of their ability during this challenging time. It has been really motivating and inspiring to see the dedication of the folks on the ground and part of what we're doing is listening and empathizing and understanding what the issues are to try to see how we might be able to work with them to find solutions.
Office for Policy in Clinical Research Operations
Carol Worrell, M.D.
Dr. Worrell provided a high-level overview of the Office for Policy in Clinical Research Operations (OPCRO) and its relationship with scientific programs within the DAIDS organizational structure. OPCRO collaborates across the Division. Since most of the OPCRO resources are geared towards the clinical trials networks, they work extensively with the following DAIDS Programs: Prevention Sciences Program (PSP), Therapeutics Research Program (TRP), and the Vaccine Research Program (VRP).
The main areas that OPCRO oversees are: policies & procedures, compliance, participant safety and study quality and integrity; development and administration of large-scale contracts; regulatory affairs oversight; and human subjects protection oversight.
OPCRO oversight of the HIV clinical trials networks process was described in detail, including protocol and informed consent development, scientific review and trial conduct.
OPCRO has responsibility for two major DAIDS clinical trials infrastructure contracts.
- DAIDS Regulatory Support Center (RSC) contract - provides comprehensive clinical regulatory support for all DAIDS-supported network and some non-network clinical trials. This support enables DAIDS to meet regulatory health authority requirements and carry out its core mission.
- NIAID HIV and Other Infectious Diseases Clinical Research Support Services (CRSS) - full-service contract provides a broad range of clinical, laboratory, and training-related services in support of clinical trials and research for HIV and other infectious diseases. The contract supports DAIDS network and non-network activities.
Support is also provided for COVID-19 pandemic related activities. OPCRO provides clinical research oversight, including regulatory affairs and human subjects protection, for ACTIV-2 trials.
Discussion: None.
The NIAID Council members voted en bloc to accept the recommendations of today’s meeting.
Ballot Voting Outcome:
The voting members of the Committee unanimously approved the new SBIR contract topic to be included in the PHS 2023-1 Solicitation for NIH and CDC SBIR Contract Proposals:
- Topic: Development of a Simian Immunodeficiency Virus (SIV) and Simian Human Immunodeficiency Virus (SHIV) Database
Future ARAC Meetings:
June 6, 2022 (virtual)
September 12, 2022
January 30, 2023 (virtual)
June 5, 2023
September 11, 2023
January 29, 2024 (virtual)
VI. Adjournment
The meeting of the Council adjourned at 4:32 p.m., on Monday, January 31, 2022.
We do hereby certify that, to the best of our knowledge, the foregoing minutes are accurate and complete.
Anthony S. Fauci, M.D.
Chair, National Advisory Allergy and Infectious Diseases Council
Director, National Institute of Allergy and Infectious Diseases
Matthew J. Fenton, Ph.D.
Executive Secretary
National Advisory Allergy and Infectious Diseases Council
Director, Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Council will formally consider these minutes at its next meeting; any corrections or notations will be incorporated in the minutes of that meeting.