The 198th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened virtually at 10:30 a.m., on Monday, June 7, 2021. Dr. Hugh Auchincloss, principal deputy director, National Institute of Allergy and Infectious Diseases (NIAID) presided as acting chair.
In accordance with the provisions of Public Law 92-463, the meeting was open to the public from 10:30 a.m. to 11:45 a.m. and from 1:00 p.m. to 3:26 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
- Review of Grant Applications
- Remarks of the Director, NIAID—Anthony S. Fauci, M.D.
- Guest Speaker—John R. Mascola, M.D., director, Vaccine Research Center
- Report of the Allergy, Immunology, and Transplantation Subcommittee—Daniel Rotrosen, M.D., director, DAIT
- Report of the Microbiology and Infectious Diseases Subcommittee–Emily Erbelding, M.D., M.P.H., director, DMID
- Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)–Carl Dieffenbach, Ph.D., director, DAIDS
- 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 5,842 research and training applications with primary assignment to NIAID for a requested amount of $1,920,237,944 in first-year direct costs and recommended approval of 2,767 applications with $1,020,912,451 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.
Consideration of Minutes of Previous Meeting
Council considered the minutes of the January 25, 2021 meeting and concepts that had been presented and approved them as written.
Appointments and Organizational Changes
Dr. Fauci announced appointments that have taken place since the last Council meeting.
Dr. Eric Lander has been confirmed by the Senate as director of the Office of Science and Technology Policy and serves as the Presidential Science Advisor.
Xavier Becerra has been confirmed as HHS secretary and Andrea Palm as HHS deputy secretary.
Dr. Vivek Murthy has been confirmed as U.S. surgeon general, and Dr. Rachel Levine as assistant secretary for health in HHS.
President Biden has nominated Dawn O’Connell as assistant secretary for preparedness and response at HHS.
Dr. Marie Bernard has been selected as the new NIH chief officer for scientific workforce diversity.
In NIAID’s Division of AIDS (DAIDS), Dr. James Cummins was selected as chief of the Preclinical Microbicide and Prevention Research Branch.
Dr. Kimberly Taylor has been named senior scientific officer of the Concept Acceleration Program for Vaccines in the Office of Biodefense Research Resources and Translational Research in the Division of Microbiology and Infectious Diseases (DMID).
Callie Prassinos has been selected as the new chief for the AIDS Research Contracts Branch in the Office of Acquisitions in the Division of Extramural Activities.
Dr. Jennifer Anderson is the new associate director for management and operations in the Vaccine Research Center (VRC).
Meetings and Events
Dr. Fauci reported on virtual meetings that have been held with international delegations and health officials. He met several times with Professor Christopher Whitty, chief medical officer for England, and Sir Patrick Vallance, United Kingdom (UK) government’s chief scientific advisor, to discuss the COVID-19 response in the United States and UK. Dr. Fauci also met with Italian Minister of Foreign Affairs and International Cooperation, Mr. Luigi Di Maio, to discuss various COVID-19 issues, and Professor Salim Abdool Karim, director of the Centre for the AIDS Programme of Research in South Africa, to discuss planned research on HIV broadly neutralizing antibodies and COVID-19.
In February, Dr. Fauci met virtually with Hans Kluge, WHO regional director for Europe, to discuss various COVID-19 issues, and UNAIDS Executive Director Winnie Byanyima to discuss HIV vaccine and therapy research, the HIV response during the pandemic, and new HIV/AIDS targets for 2025.
In March, Dr. Fauci participated in a Center for Strategic and International Studies-hosted public event with Australia’s Chief Medical Officer Dr. Paul Kelly, to discuss how the Australian and U.S. governments are refocusing their public health strategies in response to SARS-CoV-2 variants. He also met with Brazilian Minister of Health, Dr. Marcelo Queiroga, and his Brazilian colleagues to discuss the COVID-19 crisis in Brazil and potential opportunities for research collaborations.
Budget Update
Dr. Fauci began by comparing the fiscal year (FY) 2021 enacted budget with the FY 2020 final budget. NIH received an overall increase of 3.0 percent. NIAID received a 3.2 percent increase, which included $20 million for developing a universal influenza vaccine, $10 million for Lyme and other tick-borne diseases, $10 million for the NIH Centers for AIDS Research to support the Ending the HIV Epidemic in the United States initiative, and $40 million to be evenly divided among the 12 Regional Biocontainment Labs to continue efforts to prevent, prepare for, and respond to infectious disease outbreaks.
Dr. Fauci summarized NIAID’s FY 2021 financial management plan. Our R01 payline is set at the 14 percentile for established principal investigators (PIs) and the 18 percentile for new PIs. NIAID does not plan to make programmatic adjustments to noncompeting and competing grants. Competing research initiatives have been cut up to 20 percent from their planned budget level. Our estimated success rates for research project grants will be 21 to 23 percent.
On May 28, President Biden released his FY 2022 budget request, “A Budget for America’s Future,” which includes an overall increase of 21.0 percent for NIH, or $9.0 billion above the FY 2021 enacted level.
The most significant increase is $6.5 billion to establish the Advanced Research Projects Agency for Health (ARPA-H) to develop state-of-the-art tools and technologies that would “drive transformational innovation in health research and speed application and implementation of health breakthroughs.”
He provided an update on the funding NIAID received to respond to COVID-19 as well as how the Institute allocated the funds.
Legislative Update
Dr. Fauci provided updates to Senate committee leadership for congressional committees and subcommittees.
On the Senate Appropriations Committee, Senator Patrick Leahy serves as chair, and Senator Richard Shelby is now the vice chair. On the Labor-HHS Appropriations Subcommittee, Senator Patty Murray is the chair, and Senator Roy Blunt is the ranking member.
Senator Murray is also the chair of the Senate Health, Education, Labor, and Pensions Committee, and Senator Richard Burr is the ranking member.
Dr. Fauci testified at several House and Senate hearings to brief members on COVID-19, which included updates on NIAID’s role in the federal response, the safety and efficacy of COVID-19 vaccines, SARS-CoV-2 variants, and post-acute sequelae of SARS-CoV-2 infection.
In May, Dr. Fauci accompanied NIH Director Dr. Francis Collins to testify at virtual hearings of the House and Senate Appropriations Labor-HHS Subcommittees on the President’s FY 2022 NIH Budget.
Dr. Fauci briefed members of the Senate and House of Representatives on the COVID-19 pandemic, and NIAID hosted a tour of the VRC for several senators.
Dr. Fauci participated in two live televised special events that focused on the disproportionate impact of COVID-19 on minority communities, discussing vaccine access and hesitancy.
He thanked NIAID staff who have participated in many briefings and events on his behalf over the last several months.
Other Information Items
Dr. Fauci began with an update on HIV/AIDS, noting the 40-year anniversary of the first five cases of Pneumocystis pneumonia in Los Angeles. He presented the most recent statistics on HIV/AIDS from UNAIDS and in the United States, and provided updates on two randomized trials of neutralizing antibodies to prevent HIV-1 acquisition.
He continued with a COVID-19 update, summarizing the number of COVID-19 cases and deaths globally and in the United States. As of June 2, 2021, there were over 170 million cases and close to 4 million deaths globally, with more than 33 million of those cases and about 600,000 deaths in the United States.
Dr. Fauci gave an update on COVID-19 therapeutics being used, including ones that target the virus such as Remdesivir, anti-SARS-CoV-2 monoclonal antibodies, and convalescent plasma. He noted plans for a major effort to develop direct antivirals by identifying vulnerable targets on the SARS-CoV-2 replication cycle and specifically design drugs to inhibit these vulnerable targets.
He told the story behind how the COVID-19 vaccines were developed, and the multidisciplinary effort that was underway for decades before the pandemic.
Dr. Fauci presented a list of the vaccines that are currently available and those that are still waiting for emergency use authorization and completing clinical trials. He summarized the results of studies that show real-world effectiveness of the vaccines and vaccine effectiveness against viral variants and severe, critical, and fatal disease, and noted ongoing efforts to address vaccine hesitancy.
He concluded with brief updates on influenza, islet cell transplantation for Type 1 diabetes, gene therapy for adenosine deaminase deficiency, and respiratory syncytial virus.
III. Guest Speaker—John R. Mascola, M.D., director, Vaccine Research Center
Dr. John Mascola began with a brief introduction about the VRC, which was established in 2000 as an HIV vaccine center able to do basic research through to clinical trials. VRC has an integrated team of scientists that makes this possible, including immunologists, virologists, and structural biologists. The Center’s portfolio of diseases includes influenza, Ebola/Marburg, respiratory viruses, and coronaviruses.
Dr. Mascola provided a list of new and re-emerging viruses that have been infecting people and causing major outbreaks, beginning with Ebola in 1976 to COVID-19 in 2019. He noted that the COVID-19 pandemic was caused by a viral family for which we had detailed knowledge that facilitated the development of new vaccines.
He highlighted the rapid clinical development of the Moderna mRNA-1273 vaccine and contributions to Operation Warp Speed by VRC’s COVID-19 vaccine team and senior staff.
Dr. Mascola summarized VRC’s COVID-19 activities—co-development of the mRNA-1273 vaccine with Moderna and collaborating with AbCellera and Eli Lilly on discovery and development of the first COVID monoclonal antibody.
He concluded by giving an update on VRC’s work on nanoparticle-based vaccine platforms for influenza.
IV. Report of the Allergy, Immunology, and Transplantation Subcommittee—Daniel Rotrosen, M.D., director, DAIT
Dr. Rotrosen welcomed the subcommittee members to the 198th meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting.
Dr. Rotrosen presented the following scientific and Division activities:
Staff and Organizational Changes
Kathy Thompson, RNP, MSN, In April 2021, after more than 13 years of service to the Division, Ms. Thompson retired from the position of clinical protocol coordinator in the Asthma and Airway Biology Section of the Allergy, Asthma, and Airway Biology Branch, DAIT/NIAID. Ms. Thompson made important contributions to extramural clinical research especially by supporting the work of the Inner-City Asthma Consortium (ICAC) and the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR).
Padmaja Juvvadi, Ph.D., Dr. Juvvadi joined the Office of Regulatory Affairs in August 2020, as a quality assurance manager. Dr. Juvvadi received her Ph.D. in chemistry in India followed by a postdoctoral fellowship at Rockefeller University. She is an experienced Quality Assurance/Regulatory professional with extensive skills and knowledge in the areas of Quality Management, Risk Assessment, Good Clinical Practice/Good Manufacturing Practice (GCP/GMP) vendor audits, Corrective and Preventive Actions (CAPA) Management, GxP training, Document Management, Standard Operating Procedure development, Health Authority (HA) Inspection Preparedness, hosting and managing HA inspections, and more. Before joining DAIT, Dr. Juvvadi served as an expert QA consultant and as a Director of Quality Assurance for bio/pharmaceutical companies. Her experience brings added value to our team.
Madelaine Ouellette, Madelaine Ouellette joined the Office of Regulatory Affairs (ORA) in October 2020, as a health specialist. Ms. Ouellette received her bachelor's degree in biology from the Catholic University of America in 2004. Prior to joining DAIT/ORA, she was a clinical project manager at Leidos Biomedical, Inc., working on Zika and COVID-19 clinical trials. She also worked as a clinical project manager for the Henry M. Jackson Foundation for the Advancement of Military Medicine providing overall management of international acute HIV clinical trials to support cure research initiatives. Ms. Ouellette also spent several years working at Westat where she managed NCI oncology trials and monitored clinical trials as a clinical research associate monitor. Her experience with U.S. and international clinical trials operations focusing on regulatory requirements and quality assurance brings added value to our team.
Selected Funding Opportunities
NIAID
Notice of Special Interest (NOSI)—Investigations on Inborn Errors of Immunity/Primary Immunodeficiencies (NOT-AI-21-032): The purpose of this NOSI is to support the discovery and characterization of Inborn Errors of Immunity, also referred to as Primary Immunodeficiencies, understand the causes and mechanisms of disease, enable early detection and molecular diagnosis, and support the development of strategies to treat and eventually cure these disorders. Applications will be submitted using one of the following funding opportunity announcements or any reissues of these announcements through the expiration date of this NOSI: PA-20-185 (R01), PA-20-195 (R21), and PA-20-200 (R03).
Radiation-Induced Immune Dysfunction (U01, Clinical Trial Not Allowed) RFA-AI-21-019: The purpose of this request for applications (RFA) is to support studies investigating the effects of radiation exposure on the immune system and explore possible treatments for radiation-induced immune dysfunction. Research gaps exist in understanding the mechanisms of injury and repair, with regard to radiation-induced immune system dysfunction, and these gaps need to be addressed to better develop medical countermeasures (MCMs) for radiation exposure. This initiative will support the development of animal models for immune-targeted radiation injuries, studies to better understand radiation impacts on the immune system (including immune system-mediated multi-organ injury), identification of immune-specific pathways targeted by radiation, as well as biomarkers of exposure and mitigators/treatments that target immune-related radiation response pathways. The application receipt date is August 24, 2021.
“NOT-AI-21-047, Notice of Participation of the National Institute of Allergy and Infectious Diseases in PAR-21-109 Early-Stage Investigator Research Using Nonhuman Primate (NHP) Models (R21, Clinical Trial Not Allowed)” was published on April 2, 2021, to provide focused support for early-stage investigators using NHP models to conduct basic or translational research within NIAID’s mission.
Division Activities
Allergy, Asthma, and Airway Biology Branch
New Insights Into the Origins of Childhood Asthma. On February 27, 2021, as part of the virtual annual meeting of the American Academy of Allergy, Asthma, and Immunology (AAAAI), NIAID hosted a live symposium entitled “New insights into the origins of childhood asthma.” Three experts in the field presented lectures on topics including molecular and environmental determinants of asthma phenotypes in urban children, the link between severe bronchiolitis in infancy and the development of asthma, and the role of host-viral interactions in asthma development.
New Frontiers in IgE Biology. On February 26, 2021, as part of the virtual annual meeting of the AAAAI, the NIAID-funded Asthma and Allergic Diseases Cooperative Research Centers organized a live session entitled “New Frontiers in IgE Biology.” Three experts in the field presented lectures on topics including the discovery and role of T follicular helper 13 (Tfh13) cells, bone marrow reservoirs for IgE memory, and antigenic determinants of IgE-mediated peanut-induced anaphylaxis.
Prostaglandin Regulation of Allergic Disease. On February 28, 2021, as part of the virtual annual meeting of the AAAAI, the NIAID-funded Asthma and Allergic Diseases Cooperative Research Centers organized a symposium entitled “Prostaglandin Regulation of Allergic Disease.” Two experts in the field reviewed the biology of prostaglandins relative to allergic diseases.
Basic Immunology Branch
Immunity, Aging, and COVID-19 Workshop. On March 16 and 17, 2021, a workshop was held in partnership with the National Institute of Aging as a web-based meeting. The goal of the meeting was to understand host immune responses and co-morbidities in older individuals that contribute to the increased susceptibility and severity of disease in this population. Areas covered include the current knowledge of respiratory infections and vaccine responses in older adults, clinical presentations and outcomes of COVID-19, animal models, and vaccine efficacy in the elderly. Speakers discussed the gaps in knowledge, current challenges, and scientific priorities that may be pursued to reduce disease severity and improve outcomes in older adults.
B Cell Epitope and Mechanisms of Antibody Protection, Large-Scale T cell Immune Epitope Discovery and Immune Epitope Database and Analysis Resource (IEDB) Contract Annual Meeting. On March 10 and 11, 2021, the contractor annual meeting was held virtually to bring together the contractors from these two epitope discovery programs, the IEDB, NIAID staff involved in these programs, and other interested NIAID staff. The purpose of these programs is to support highly interactive, multidisciplinary teams whose research efforts are focused on large-scale discovery of immune epitopes and antibodies associated with infectious or autoimmune diseases, and validate these epitopes regarding their role in immune protection or immune-mediated pathogenesis in humans. This meeting provided a venue for the project investigators to provide updates on project progress and to develop scientific collaborations with each other to foster program success. Contractors who expanded their contract work to include epitope discovery and evaluation of antibody protection for SARS-CoV-2 also presented their findings at this meeting.
Human Immunology Project Consortium II (HIPC II) Annual Meeting. On March 24 and 25, 2021, the HIPC program annual meeting was held virtually. The HIPC II program (http://www.immuneprofiling.org/) is composed of nine U19 cooperative agreement awardees and is designed to characterize molecular profiles of human immune responses to infection or vaccination using systems immunology approaches. All of the data generated by the HIPC investigators are being made available to the broader research community through ImmPort (http://www.immport.org) and ImmuneSpace (https://www.immunespace.org/), which is an engine for exploration and analysis of HIPC-generated datasets. In addition, HIPC investigators, led by the Yale HIPC team, have developed an Immune Signatures database to make HIPC-generated immune signature accessible and comparable and to identify common and unique immune signatures that predict responses to different vaccine types (http://hipc-dashboard.org). The HIPC II program is co-led by the Basic Immunology (BIB) and Allergy, Asthma ,and Airway Biology Branches (AAABB) within DAIT, NIAID, and co-funded by all three NIAID extramural divisions (DAIDS, DMID, and DAIT), each of which also provide programmatic oversight for the individual HIPC awards.
Characterizing and Improving Humanized Immune System Mouse Models. On April 21, 2021, an interim progress meeting was held virtually. This meeting included research updates from three existing contracts (awarded in 2020) and one newly awarded project. The contractors described their recent progress in optimization and testing of non-fetal human tissues (cord blood hematopoietic stem cells, neonatal tissue) or porcine thymic tissue to reproducibly reconstitute and maintain human immune cells in the blood, lymphoid, and non-lymphoid tissues of various mouse models. The fourth project also includes direct comparisons of humanized immune system mice made from banked fetal and neonatal human tissue sources.
Immune Mechanisms at the Maternal-Fetal Interface. On April 27, 2021, the second annual meeting of the program to evaluate immunity at the maternal-fetal interface was held virtually. The program supports 11 projects that include investigators from Wayne State University, University of Pittsburgh, Duke University, University of California at San Francisco, Rutgers Biomedical and Health Sciences-New Jersey Medical School, University of California Irvine, Seattle Children’s Hospital, University of Pennsylvania, University of Alabama, Birmingham, and Boston Children’s Hospital. 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.
Immunity to SARS-CoV-2 Infection. On May 12, 2021, a two-hour American Association of Immunologists Guest Symposium was held at the Virtual Immunology 2021 Meeting. The session highlighted recent advances in our understanding of innate and adaptive immune responses triggered by SARS-CoV-2 infection, and their role in prevention from or contribution to disease progression or resolution. Presenters included Drs. Shane Crotty, Bali Pulendran, Ingnacio Sanz, and E. John Wherry.
Transplantation Branch
HLA and KIR Region Genomics in Immune-Mediated Diseases Program. On April 6, 2021, the kick-off meeting for the HLA and KIR Region Genomics in Immune-Mediated Diseases Cooperative Agreement program, consisting of five U01 awards, was held via videoconference. Renewed in 2020, the program supports studies that seek to identify and characterize associations between polymorphisms in human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genetic regions and immune-mediated disease risk, progression, and/or severity, including outcomes following organ, tissue, and cell transplantation; and continues support for the generation of high quality, publicly accessible HLA- and KIR- genomic data sets and associated phenotypic data. Consortium members, extramural staff from NIAID, and co-funding institutes, NCI and NINDS, attended the meeting, which included presentations on project goals, approaches, and progress to date. A group discussion was held on opportunities for collaboration between projects, analytical tools and approaches, and platforms for data sharing.
Emerging Science and Technology in Transplantation Research Program. On October 14, 2020, the annual Emerging Science and Technology in Transplantation Research Steering Committee Meeting was held via videoconference. This program supports six U01 projects focused on transplantation immunology research in three priority areas: 1) microbiota; 2) intravital imaging; and 3) targeted therapeutic delivery. The goal of this program is to stimulate and support innovation in transplantation immunology through the application of scientific developments and technologies that have not been widely used in transplant immunology research in order to gain novel insights into fundamental aspects of the alloimmune response and reveal new avenues to prevent rejection and prolong graft survival.
Immunobiology of Xenotransplantation Cooperative Research Program. On November 6, 2020, the kick-off meeting of the 5th iteration of the Immunobiology of Xenotransplantation Cooperative Research Program (IXCRP), consisting of three U01 awards and one U19 award, was held via videoconference. The program currently supports preclinical research in porcine-to-nonhuman primate models of pancreatic islet, kidney, and liver xenotransplantation designed to 1) delineate the cellular and molecular mechanisms of xenograft rejection and/or the induction of immune tolerance; 2) develop effective strategies to improve xenograft survival; and 3) characterize and address the physiological compatibility limitations of xenografts. The long-term goal is to develop xenotransplantation strategies for clinical application. The kick-off meeting provided an opportunity for investigators to present work-in-progress and future directions. They discussed potential collaborations, available animal models, and reagent resources. Guest speakers from the National Swine Research and Resource Center provided an update on swine strains developed in collaboration with IXCRP investigators during the previous funding period.
Autoimmunity and Mucosal Immunology Branch
Development of Sample Sparing Assays for Monitoring Immune Responses. On April 1, 2021, investigators and their teams who received an award under this program met virtually for their kickoff meeting. This program is a partnership between the Division of AIDS and DAIT. The goal of the program is to develop cutting-edge assays that will enable complex immune monitoring from small volume samples derived from human subjects. The sample sparing assays under study include diverse technologies and span several areas of serology, virology, immune cell function, and proteomics. One project received supplement funding in summer 2020 to study SARS-CoV-2 serology. Investigators presented recent updates and progress in each of their projects.
Accelerating Progress in Celiac Disease Research Workshop. On March 18 and 19, 2021, NIAID and NIDDK co-sponsored a virtual workshop that brought together a diverse group of 40 experts in celiac disease and related scientific areas to discuss research focused on celiac disease. The goal of the workshop was to identify opportunities for future research, research gaps that impede future development of therapies and prevention strategies, and opportunities for research and training of future investigators; and inform the research community about possible avenues for future research and collaborations. The scientific sessions provided an overview of celiac disease and covered the topics of disease models, immunology of celiac disease, emerging areas of research, and diagnostics and therapeutics. Speakers and invited discussants participated in discussion sessions focused on innate immunity, adaptive immunity, disease triggers and prevention, and therapeutics. Each session considered responses to the following questions:
- What are the gaps in celiac disease research relevant to this session area?
- What types of opportunities would accelerate the pace of research in this session area?
- What are the impediments to future investigators in terms of entering the field, training opportunities, and establishment of independence in this session area?
- What expertise and resources are needed to make research progress?
The feedback provided will inform NIH on how to better promote and support research focused on celiac disease. Due to broad interest from the celiac disease patient and research communities, the scientific sessions were broadcast for the public.
Radiation and Nuclear Countermeasures Program
U01 Novel Bioassay and Biodosimetry Devices Kickoff Meeting. On January 11, 2021, the NIAID/RNCP conducted a virtual kickoff meeting for the newest U01 consortium that is focused on “Novel Bioassays and Biodosimetry Devices.” The objectives of the meeting were to allow the investigators to meet in a forum that allowed for creative interactions and to provide background on their planned projects (as well as some of their progress since being awarded in 2020). The meeting provided for exchange of ideas and refinement of research, while providing a framework for future collaborations among the investigators. The meeting was attended by the PIs, NIAID staff, regulatory agency members, and other U.S. government agencies (over 75 attendees). Plans were elaborated for collaborations within the consortium for the upcoming year.
Annual U01 Radiation-Induced Vascular Injury Meeting. On January 28, 2021, the NIAID/RNCP conducted the fourth annual U01 investigator meeting for the funded RFA on “Elucidation of mechanisms of radiation-induced endovascular injury and development of treatments/mitigators for radiation-induced endothelial cell and vascular dysfunction.” The objectives of the meeting were to provide an update on the progress made in the respective U01 grants over the past year, exchange ideas for refining the research, and allow the PIs to provide updates on collaborative projects initiated during the prior year. The meeting involved project PIs, NIAID and other institute and center (IC) staff, representatives from regulatory agencies, and other parts of government that have overlapping scientific interest.
NIAID/BARDA Inter-Agency Update Meetings. On January 13, 2021 (biodosimetry) and March 22, 2021 [medical countermeasures (MCM)], members of the NIAID RNCP met with program managers responsible for biodosimetry and MCM development within the Biomedical Advanced Research and Development Authority (BARDA). These biannual meetings (held regularly since 2014) at the request of the HHS assistant secretary of preparedness and response (ASPR), are to provide programmatic transparency, ensure that funded radiation research across HHS continues to be aligned, and confirm there is no scientific overlap between the research portfolios.
ARS Action Team Meetings with FDA’s Office of Counterterrorism and Emerging Threats (OCET). On March 1, 2021, the RNCP met with OCET’s MCM Regulatory Science Team to discuss respective COVID-19 research efforts and explore potential opportunities for collaboration. On March 9, 2021, the RNCP and FDA met in collaboration with the NIAID Bioinformatics and Computational Biosciences Branch (BCBB) to present progress made on the development of an Immersive Visualization of Cutaneous Radiation Injury (CRI) model. This model combines information obtained from 3-dimentional CT imaging and radiation dosimetry data to create a visual representation of underlying tissue topology, allowing for more accurate analyses to refine RNCP’s current CRI model.
NIAID/NIDDK Intestinal Stem Cell Consortium (ISCC) Bi-Annual Update Spring 2021 Meeting. On March 15 and 16, 2021, the NIAID/NIDDK ISCC bi-annual meeting was held virtually, with coordination by NIAID Meet. Each of the awarded U01 teams provided an overview of the research conducted to date and discussed collaborative topic areas the consortium is exploring. The purpose of this meeting was to allow researchers an opportunity to provide an update on their progress, and foster dialog and collaboration among the ISCC investigators and program staff, regarding future research and development directions.
FY 2023 Research Concept Clearances Presented to Division Advisory Council
The subcommittee endorsed and unanimously approved the following three research concept clearances:
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SUNBEAM-Analysis and Bioinformatics Center (ABC) (UM1, Clinical Trial Not Allowed)
This initiative will support the detailed molecular analysis of cord blood and peripheral blood collected from the participants in the SUNBEAM birth cohort study. Studies include but are not limited to blood transcriptomics, high parameter analysis of blood cells, proteomics, and metabolomics. -
Limited Competition to Continue the PARK Trial
This initiative will support the two-year follow-up of the enrolled participants to completion and analysis of this clinical trial. -
Development of Microbiome-Related Approaches for Diagnosis/Mitigation/Treatment of Radiation Injuries (U01, Clinical Trial Not Allowed)
This initiative will support the research and development of microbiome-related approaches to diagnose/mitigate/treat acute radiation syndrome (ARS) and the delayed effects of acute radiation exposure (DEARE).
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 June 7, 2021. She provided a DMID personnel update, recognizing new staff appointments made in the Division since the last Council meeting, including Belete Teferededegne, Office of Regulatory Affairs; Rajeev Gautam, Virology Branch; Debbie Bratt, Respiratory Diseases Branch; Aya Nakamura, Office of Clinical Research Activities; and Tamika Samuel, Bacteriology and Mycology Branch. She also noted that Kim Taylor in the Office of Biodefense, Research Resources and Translational Research will now serve as the senior scientific officer for the Vaccine Concept Acceleration Program.
Following staff introductions, Dr. Erbelding reported on several activities, including:
- The status of COVID-19 vaccine candidates, noting that DMID staff have played a significant role in protocol development for several of the clinical trials for these vaccines. She reported that clinical trials evaluating several of the vaccine candidates in pediatric populations are enrolling or ongoing.
- Swab your Nose to Find inFection (SNFF) clinical trial, an ancillary swab study to the Novavax Pediatric Expansion Phase 3 Trial of a COVID-19 vaccine that will look for asymptomatic viral shedding of COVID-19. The study is being conducted through DMID’s Vaccine and Treatment Evaluation Units.
- The Adaptive COVID-19 Treatment Trial, which is coming to a close following several iterations designed to evaluate therapeutics for COVID-19. She noted that NIAID remains actively engaged in Accelerating COVID Therapeutic Interventions and Vaccines, a public-private partnership to develop a coordinated research strategy for prioritizing and speeding development of the most promising treatments and vaccines.
- SARS-CoV-2 Interagency Working Group (SIG), an interagency group tasked with making recommendations to mitigate COVID-19 morbidity and mortality based on risk assessment of the potential impact from emerging SARS-CoV-2 variants on the effectiveness of vaccines, therapeutics, diagnostics, and public health control efforts. She described the structure of the SIG and noted that she and several other DMID staff members serve on the working group.
- “Dalbavancin as an Option for Treatment of S. aureus Bacteremia (DOTS)” clinical trial, which is being conducted through the DMID-supported Antibacterial Resistance Leadership Group and will test the effectiveness of Dalbavancin as a treatment for Staphylococcus aureus bacteremia.
Dr. Erbelding presented a late-breaking FY 2022 concept for clearance, Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern (U19, Clinical Trials Not Allowed), which would support innovative antiviral drug discovery and development targeting coronaviruses (CoVs), emphasizing SARS-CoV-2, and select RNA viruses with pandemic potential with the goal of developing new antivirals that can be used in the outpatient setting. One Subcommittee member asked about the types of products to be supported under the proposed program and whether host-targeted antivirals are within the scope of the concept, noting that these types of products have potential advantages over direct-targeting antivirals. Another Subcommittee member also voiced support that such efforts be considered under this new program. Dr. Erbelding thanked the members for their input and said she would take these points under consideration.
FY 2023 Concepts Presented for Clearance
Fundamental Research to Understand the Mechanisms of Neurotropic Virus-Mediated Disease (R01, Clinical Trial Not Allowed)–This concept would support fundamental research into mechanisms that lead to neuropathogenesis after acute viral infection of the central nervous system (CNS). The Subcommittee members expressed strong support for the concept, noting the need for a better understanding of viral neuropathogenesis for less-studied emerging and re-emerging neurotropic viruses for which there are currently no approved vaccines or therapeutics. The Subcommittee members raised concerns about potential difficulty in finding suitable reviewers, given that many investigators in this relatively small area of focus may apply. Another Subcommittee member asked if this would include studies into long-term neurological effects of chronic viral infections. Program acknowledged the concern about reviewer availability and also clarified that, although infections caused by many of the viruses of interest can result in long-term neurological sequelae, the intent of this concept is to support studies that focus on processes underlying the acute phase of viral infections of the central nervous system. This would in turn provide a solid foundation for future research into long-term effects caused by these neurotropic viruses. The Subcommittee approved the concept.
Host Immunity and Novel Immunization Strategies for Clostridioides difficile Infection (CDI) (U19, Clinical Trial Not Allowed)–This concept would advance novel immunization strategies aimed at protecting individuals from infection with the nosocomial pathogen, Clostridioides difficile. DMID Subcommittee members voiced strong support for the concept and noted that available therapeutics do not address primary prevention of disease. Program provided a landscape analysis of the current CDI vaccine pipeline and addressed the utility of animal models, noting that hamsters and mice, while not ideal, do provide a reasonable approximation of vaccine immunogenicity and efficacy. New and emerging microphysiological systems (e.g., coloniods) have the potential to provide an alternative test system but the technology has not advanced to the point of realizing this goal. The Subcommittee approved the concept.
Advancing Group A Streptococcus (GAS) Vaccine Discovery (R01, Clinical Trial Not Allowed)–The goal of this concept is to promote basic and translational research to advance GAS vaccine discovery. The Subcommittee members expressed strong support for the concept, noting a worldwide need for prevention of GAS infections. The Subcommittee members acknowledged that the intent of the concept’s broad scope is to stimulate the research community and expand the current GAS vaccine portfolio. The Subcommittee members recommended inclusion of research involving human samples. Program staff confirmed that proposed studies could utilize human cells, tissues, and pre-existing samples. The Subcommittee approved the concept.
Identification and Characterization of Persistence Mechanisms of Protozoan Pathogens (R01, Clinical Trials Not Allowed)–This concept would support basic and preclinical research to characterize persister stages in selected protozoan infections. The Subcommittee voiced strong support for the concept, noting that studying persistence in the pathogens selected represented a diverse and understudied area of research and presented the potential for the discovery of novel therapeutic targets and strategies. Additionally, the use of advanced technologies such as single cell analytics and sequencing, with a focus on in vitro and in vivo modeling, make new analyses and the testing of small molecules and immunotherapeutics possible. Finally, the concept would provide an opportunity to better understand the different mechanisms used by pathogens to enter and exit persistent states, which could be of broad interest to non-parasitology research communities with the potential to uncover novel phenomena of fundamental and practical importance beyond these diseases. The concept was approved.
Systems Biology for Infectious Diseases (SysBioID) (U19, Clinical Trials Not Allowed)–This concept renewal would support research that employs a systems biology approach across a wide array of pathogens to rapidly transform large datasets into predictive models that complement and guide in vitro, in vivo, and clinical studies. The Subcommittee members underscored that the program should focus on activities that integrate diverse, clinically relevant data types across multiple DMID priority pathogens. They suggested that the concept scope should include both established and less studied pathogens and leverage existing infectious disease infrastructure. Finally, they highlighted that the concept’s emphasis on technology development is ideal for encouraging new and early-stage investigators to lead Projects and Cores. Program agreed with these recommendations, and re-iterated that each of the recommendations are in line with the concept objectives. The concept was approved.
VI. Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)–Carl Dieffenbach, Ph.D., director, DAIDS
Welcome and Approval of Minutes
Kenneth A. Freedberg, M.D., M.Sc., (Chair)
Dr. Freedberg welcomed everyone and the ARAC members approved the minutes of the January 25, 2021 meeting.
Director’s Report and SBIR Contract Topic
Carl Dieffenbach, Ph.D.
Dr. Dieffenbach introduced several new ARAC members: Elaine J. Abrams, M.D.; Reuben S. Harris, Ph.D.; Stephaun E. Wallace, Ph.D.; and Richard T. D’Aquila, M.D. Other introductions were Demetre Daskalakis, M.D., M.P.H. as the new CDC liaison to the Committee. Dr. James Cummins, Ph.D., will replace Dr. Jim Turpin, who retired earlier this year, as the new chief of the Preclinical Microbicide and Prevention Research Branch in the DAIDS Prevention Sciences Program.
Budget Update
The average increase across NIH was approximately 3 percent and was 3.2 percent for NIAID. Notably, the National Institute on Aging (NIA) received a 10 percent increase, $300 million for Alzheimer’s research. The NIH OD received a 5.6 percent increase that was driven by a $75 million increase to support biomedical innovation in the computational sciences such as artificial intelligence. Within NIAID a 3.2 percent budget increase was received; $20 million was for universal influenza vaccines, $10 million for Lyme and tick-borne diseases, $10 million for the NIH Centers for AIDS Research (CFAR) to support activities for Ending the HIV Epidemic in the United States, and $40 million which was equally divided among the 12 regional biocontainment laboratories that were initially funded in 2003 to continue efforts to prepare for infectious disease outbreaks. This marks the sixth consecutive year that NIH has received a significant budget increase.
The NIAID FY 2021 financial management plan listed various paylines where the R01 paylines would be held to the 14th and 18th percentiles for established and new PIs respectively. There will be a cut in competing research initiatives of up to 20 percent and estimated success rates across the Institute are expected to be between 21 and 23 percent.
On May 28, the President submitted the FY 2022 budget request to Congress, proposing an overall increase for NIH of $9 billion or 21 percent over the FY 2021 level. The most significant line item shown in a summary table of the budget is the new proposal called ARP-H (Advanced Projects Agency for Health) for $6.5 billion. This proposal is modeled after the DARPA model, but it is not currently clear whether it will reside within NIH, or in NIH as a separate entity or will be merged with another of the institutes. In addition, the $6.5 billion represents three years of funding. While the future of this proposal is not at all clear, it will be discussed in some detail when more about it is known. The initial focus areas for ARP-H include cancer, diabetes, and Alzheimer's. Many other institutes received between 3 percent and 5 percent increases. Of note, NIDA is receiving a 25.1 percent increase to expand opioids in pain research as part of the Helping to End Addiction Long-term (HEAL) initiative. The 8.2 percent increase for other institutes/centers (ICs) was driven largely by the expanding research on opioids and pain research. NIAID’s percent increase was similar to many other institutes, including an earmark of $10 million for the CFARs focused on the Ending the HIV Epidemic initiative. The House Appropriations Committee has scheduled earmark markups and hearings for late June; the Senate committee has not announced a timetable yet. Until the final FY 2022 budget is passed, we will remain conservative in our paylines.
Discussion:
Q: Are the CFARs, through NIAID, a way to help support early-stage investigators (ESIs)?
A: The payline at NIAID for new investigators is a 4 percent bump over the established investigators level. The CFARs actually play an important role through the developmental projects because they help to boost the new investigators. We believe that analyses have shown that investigators at institutions with CFARs do a lot better than those from institutions that doesn't have a CFAR. The better payline does a reasonable job of providing early investigators an adequate boost to get started.
OAR Activities to Support HIV Early-Stage Investigators (ESIs)
The NIH Office of AIDS Research (OAR) has been working with NIH institutes to provide a sustainable framework to support HIV ESIs and provide opportunities for young investigators. An OAR taskforce will continue to address difficulties that ESIs face in obtaining funding needed for independence.
A list of OAR activities to support ESIs was reviewed: continue partnerships with NIH ICs to support ESI R01 awards; conduct NIH-wide portfolio analyses of HIV ESIs, including analyses of K awardees later obtaining R01 grants; conduct listening sessions (conversations) with NIH staff and ESIs to obtain stakeholder feedback, including effects of COVID-19 pandemic on ESI research; convene an expert panel to discuss strategies to support, retain and expand the pool of HIV ESIs, including opportunities for enhancing support and engagement of a diverse ESI workforce; and future symposia with ESIs for presentations of their data and networking.
Updates will be provided at OARAC meetings and will be shared at future ARAC meetings in the OARAC updates.
Scientific and Programmatic Updates
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)
In the NIH response to the pandemic, on the therapeutic side, we have seen the formation and implementation of ACTIV or Accelerating COVID-19 Therapeutic Interventions and Vaccines across a large number of trials, ACTIV-1 through 6. NIAID is heavily involved in ACTIV-2, which deals with outpatient studies and ACTIV-3, which deals mainly with inpatient studies. Our sister NIAID Division, the Division of Microbiology and Infectious Diseases (DMID), plays a major role in ACTIV-5, which are the big effect trials that are looking at proof of concept studies in hospitalized adults. These continue to report out and advance the important molecules, such as the work that ACTIV-2 has done with the Lilly, Brii Biosciences, and AstraZenica monoclonals, as well as other investigational products. ACTIV-3 has looked at a range of molecules and including similar antibodies. Many of our trials have international sites now, so that this work can continue to a point where we will get better medications for the treatment of early COVID disease.
The current SARS-CoV-2 antibody landscape and range of vaccine candidates being evaluated through the ACTIV program, the COVID-19 Prevention Network (CoVPN), and Operation Warp Speed were presented.
The antibody landscape with partner companies was summarized; three have been successful: Lilly, Regeneron, and the Vir/GSK collaboration.
In terms of vaccine candidates, Operation Warp Speed (OWS) was heavily involved with the BioNTech/Pfizer vaccine, and that EUA has been issued down to age 12. The Moderna RNA vaccine has an EUA for down to age 18 and has just filed internationally in the European Union down to age 12. Moderna has now filed for full licensure with their BLA application submitted to the FDA last week. Janssen has an EUA down to age 18. The AstraZeneca and Novavax vaccines are fairly well along in their Phase III trials; both have been closed and EUA submissions are pending for both. The Sanofi Phase III trial is currently opened and actively enrolling. These are remarkable achievements, and we all should take a moment and just marvel at how rapidly this went and the high-quality work that contributed to these vaccines in the U.S. and globally.
40 Years of Progress
This week, June 5, marked 40 years since the first MMWR reporting on cases of Pneumocystis carinii pneumonia from California. Key events and milestones during this time included the transformation of HIV/AIDS from a fatal disease to a manageable chronic illness. The leadership of the U.S. government through the PEPFAR Program has brought medications to the globe and has seen a profound impact on survival globally.
We recognize that there have been over 32 million deaths from HIV-related illness globally since the start of the epidemic; numerous efforts to ensure equitable access to services for the 38 million people living with HIV globally; leadership, unity, and compassion in the HIV response; and a recommitment to the goal of ending the epidemic in the United States and across the world.
Several commemorative events by the U.S. government include coordinated efforts across the federal agencies and non-federal partners to end the HIV epidemic and focus on the Four for Forty themes: Reflect, Recommit, Re-energize, and Re-engage.
Ending the HIV Epidemic (EHE): A Plan for America
2020 EHE Awards to CFARs and ARCs
In FY 2020 we were able to make a number of awards that covered the different pillars. We had nine in the Diagnosis pillar, 27 in Prevent, 12 in Treat, and three in Respond. We were able to get activities going in 20 counties and four of the seven states that represented the initial target jurisdictions.
2021 CFAR/ARC EHE Supplement Topics
Several activities were initiated in terms of implementation research. These were locally driven strategies developed and implemented with community partners and focused on collaboration with researchers from historically black colleges and universities and included planning projects to address social and structural determinants of HIV using an intersectional framework, in a partnership with community to enhance efforts to address the needs of community.
FY 2022 NIH EHE Funding Opportunity Announcements (FOAs)
NIH recently published three EHE FOAs for funding in FY 2022:
- Multidisciplinary Treatment Approaches to End the HIV Epidemic (RFA-AI-21-024)
- Prevention Strategies to End the HIV Epidemic (RFA-AI-21-025)
- Respond: Epidemiology to End the HIV Epidemic (RFA-AI-21-023)
Each encourages applicants to develop creative, locally defined, and culturally-sensitive strategies with local implementing and community partners to address local EHE priorities.
SBIR Contract Topic (New)
A new SBIR contract topic for submission to the FY 2022 solicitation was presented for approval vote, Development of Diagnostics to Differentiate HIV Infection from Vaccine Induced Seropositivity (VISP). The goal of this project is to support the development of new serological and nucleic acid assays that can identify HIV infection while avoiding false-positive results due to VISP, with high sensitivity and specificity. These next-generation assays should be developed to address one or all applications/indications of HIV tests, namely: 1) laboratory-based tests, 2) point-of-care and clinical practices, and 3) self-testing. Ideally, these assays should be scalable and adaptable for manual performance (point-of-care, medical practices, and self-testing) as well as fully or partially automated for high-throughput (medical laboratories). They can be developed for performance in already existing, commercially available platforms and automated equipment or for performance using new devices. Examples of phase I and II activities were listed and included development of target product profile and assay performance indicators.
Ballot Voting Outcome:
12 Approval
0 Approval with modification(s)
0 Deferral for further information
0 Disapproval
A slide listed upcoming meetings and dates:
- June 8, 2021 (Strategic Working Group (SWG))
- September 13, 2021 (ARAC)
- September 14, 2021 (SWG)
- September 15, 2021 (AIDS Vaccine Research Subcommittee (AVRS))
- January 31, 2022 (ARAC)
- June 6, 2022 (ARAC)
- September 12, 2022 (ARAC)
- January 30, 2023 (ARAC)
- June 5, 2023 (ARAC)
- September 11, 2023 (ARAC)
Discussion:
Q: Was additional funding given to NIH for the End the HIV Epidemic (EHE), or was it from existing funds? And did that represent more of an interest in research to the HRSA and CDC efforts?
A: It was decided as part of our EHE activity that it was time for us to take a leadership role and provide our own funding, hoping that we would get an appropriation for EHE. For next year, there is additional EHE money in the requested budget. It is currently focused on CFARs but it may be adjustable. It was felt, in collaboration with the partnerships with NIMH and OAR, to put these forward in a way that would be maximally useful to the research community in terms of these kinds of implementation questions that needed to go forward.
Q: Is there clarity on the schedule for booster shots? Is there work being done on all the available vaccines to determine when boosters will be needed?
A: On the COVID side, we are working that out with Moderna and Pfizer as we speak. There are two issues: 1) declining efficacy, does the vaccine response wane and is there a diminution in immunity that will need a booster? Also, 2) are there variants of concern that will necessitate the need for booster shots? There is currently monitoring of the durability of vaccine responses through a variety of mechanisms. At the same time, we're working up the processes to look at boosting.
Q: How about an advocacy for Operation Warp Speed for HIV and TB vaccines?
A: There are a lot of lessons that can be learned from OWS and the tools and technologies that we brought forward for HIV vaccines [to the HVTNs credit] in collaboration with what has been done so far. Moderna has made three different HIV envelope RNA vaccines, which are either just entering Phase I or about to enter Phase I.
It was noted that Operation Warp Speed has formally transitioned into a permanent structure within HHS so we can continue to rely on its important functions to respond to this pandemic as well as better prepare for future threats. Operation Warp Speed is now called the Countermeasures Acceleration Group (CAG).
Office of AIDS Research Advisory Council (OARAC) Update
Tricia H. Burdo, Ph.D.
Highlights of the 56th OARAC meeting on February 25, 2021, were presented. This included the OAR Director’s Report from the NIH Associate Director for AIDS Research, HIV Antiretroviral and OI Guidelines Working Groups, NIH Advisory Council, Directors of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Center for Advancing Translational Sciences (NCATS), and a report-out from the OAR ESI Taskforce.
OAR Director’s Report
The high levels of alignment between the newly released HHS HIV National Strategic Plan for Ending HIV in the United States: A Roadmap to End the Epidemic for the U.S. 2021-2025; NIH Strategic Plan for HIV and HIV-related Research; and Ending the HIV Epidemic was presented. Also covered was an overview of research advances—HPTN 083 and HPTN 084 and AMP trials; the NIH HIV research budget; various OAR outreach and engagements; and release of an OAR HIV stakeholder outreach and engagement report.
HIV Antiretroviral and Opportunistic Infections (OI) Guidelines Working Groups of OARAC
Key points from this presentation included:
- The major change for the perinatal guidelines is to move towards more inclusive language and content to address the care of transgender and non-binary people who are pregnant or trying to conceive, and inclusion of a new section about PrEP to reduce the risk of contracting HIV during preconception, antepartum, and postpartum periods.
- Additional content included guidance on telemedicine with a new table that outlines requirements for in-person versus telemedicine visits, and additions to the adolescents and adult opportunistic infection guidelines.
- The adult and adolescent guidelines contain strong recommendations for the use of the long acting injectable cabotegravir and rilpivirine.
- The guideline recommends that all persons with HIV who receive the COVID vaccine and COVID-19 patients with or without HIV should be treated similarly. Sections of the guideline regarding children and pregnant women with HIV and COVID-19 have also been updated and can be found in the OAR minutes and on the website.
NIH Advisory Council Updates and NIBIB and NCATS Presentations
Reports were presented from each of the advisory Councils. Details can be found on the website. For NIBIB and NCATS there were presentations on bioengineering for rapid acceleration for COVID-19 diagnostics and implications of COVID across translational science for HIV research.
OAR ESI Taskforce Report-Out
This taskforce, previously alluded to by Dr. Dieffenbach in his Director’s Report, has identified HIV ESI awards between 2015 and 2020 and compared them to overall NIH trends since the publication of the NIH OD’s Next Generation Research Initiative in 2017. It plans to design a sustainable framework to promote or enhance support of HIV ESIs. Activities slated for 2021 include continuing the partnerships with the NIH ICs, ESI listening sessions, an expert panel of consultation and an ESI symposium.
OARAC membership changes were noted. OAR’s coordination of the NIH commemoration of the MMWR 40th anniversary was highlighted.
Next OARAC meeting: June 24, 2021 (Virtual Meeting)
Discussion: None
Therapeutics Research Program
Development of Assays for Testing Susceptibility to Broadly Neutralizing Antibodies (bNAbs)
Keith W. Crawford, R.Ph., Ph.D.
The objective of this new initiative is to develop an assay to test for susceptibility to broadly neutralizing antibodies (bNAbs) in participants’ samples and screen out those who carry resistant virus before they are entered into clinical trials. In brief, this initiative supports the development of clinical laboratory assays to measure susceptibility to bNAbs and individuals living with HIV. Problems may occur in trials involving bNAbs as individuals enrolled may not know whether they are even susceptible to the antibody and their potential pre-existing resistance to the bNAbs. This could confound the results of the study and waste valuable resources. Therefore, knowing upfront if individuals are sensitive would be good for excluding them from participating in the studies. Challenges include detecting bNAbs in virally suppressed individuals, a lack of defined clinical cut-offs for clinical susceptibility and pseudovirus creation is time consuming and expensive.
A phased innovation (R61/R33) mechanism is proposed involving an early-stage method development followed by verification and late-stage validation of the method. Not all investigators will advance to the later stage if predetermined, negotiated milestones have not been reached. The reviewers’ comments and suggestions for this initiative were summarized and responses to them were discussed.
Ballot Voting Outcome:
12 Approval
0 Approval with modification(s)
0 Deferral for further information
0 Disapproval
Discussion:
Q: Could you briefly summarize the data that indicate that resistance is pre-existing versus potentially acquired during bNAb therapy?
A: Some observations were that even though individuals were not screened, prior to actually being enrolled in the study, they had samples collected before being exposed to the broadly neutralizing antibodies. So, in those pre-treatment samples, they found the resistance indicating that it was pre-existing.
Q1: In the R61 phase, would animal model research, specifically SIV infection in nonhuman primates, be eligible?
A: This is a diagnostic, it's not a therapeutic, it's not an agent being developed for prevention. It's not something that's going to go into individuals. Perhaps animals could be used to test the sensitivity and specificity and other parameters of your diagnostic. But that would be up to the investigator to propose.
Comment: I'm thinking that the blood may not be the compartment where the resistant virus is to be found. So, getting tissues in an animal model might be helpful to understand if that's one of the challenges to overcome.
A: Excellent point. This is one of the reasons why some of the available assays may not produce the most accurate results. Finding the right cell type, accessing those cells, such as getting it from the blood PBMCs maybe not the best source, but then you start talking about more invasive measures, possibly getting into the reservoir getting maybe a better type of tissue that might better reflect what's actually in the reservoir.
Q2: RE: the rationale for this program. Is it because we're concerned about individuals who are participating in studies of bNAbs having an early virologic rebound, and we want to prevent that from happening? Or is in anticipation that bNAbs will have therapeutic value and we want an assay available for that moment in time?
A: It is going to be quite challenging. That's one of the reasons why we will release this as an RFA, because we don't have the answers or see a pathway to it, putting it out to the ingenuity and creative thinking of the research community, there is someone with an answer. There are some published studies where people have made some headway into developing assays that may be able to predict that.
As to whether our focus is on the clinical trials and are we looking at something when these products become clinically available? The answer is both. When these products become available commercially, approved by the FDA, we will need an assay. So, the goal is whatever is developed can be developed later or expanded or modified to be used as a commercial assay.
Ballot Voting Outcome:
12 Approval
0 Approval with modification(s)
0 Deferral for further information
0 Disapproval
Regional Prospective Observational Research in Tuberculosis (RePORT)
Sudha Srinivasan, Ph.D., M.P.H.
Three concepts as proposed future initiatives were presented in a condensed RePORT presentation: RePORT International Coordinating Center (RICC), RePORT Brazil, and RePORT South Africa. The NIAID Strategic Plan for TB Research which guides the TB research activities is of special interest to date given the impact of TB disease for persons living with HIV. This is also closely aligned with the WHO recommendations and the U.S. government research activities in support of the global End TB Strategy. The RePORT platform, a global research network, addresses three important tenets of the strategic framework. This includes expanding fundamental knowledge of TB; improving TB diagnosis, prevention, and treatment; and to support the development of tools and resources to support TB research through global coordinated research. The importance of the global research networks was listed and included that TB is among the leading infectious disease killer especially for people living with HIV. The networks will enhance regional research capacity. RePORT International is a consortium of collaborative prospective observational research networks in six high TB/HIV burden countries and are jointly or fully funded by participating countries. The RePORT common protocol was described and comprises an active TB cohort and a household contacts cohort. The countries that implement this common protocol collect a minimum set of samples and data at pre-specified time points which are processed and curated as prescribed.
The RePORT consortia investigators are engaged in a range of focus areas from diagnostics, validation, and development, prognostic biomarkers, looking at host pathogen interactions, supporting preclinical research for vaccine development, looking at trends, TB transmission, particularly in patients who are people living with HIV.
The purpose of the RICC is to catalyze on TB and HIV research to improve health outcomes, particularly among people living with HIV. The objective is to enable coordination and acceleration of TB and TB/HIV research, not only across the RePORT consortium member countries, but also with the external research community. Some of the most important research and support functions of RICC are to identify, catalyze, and guide TB/HIV research among the networks and with external partners. The RICC will establish and manage the Data Management Hub including data harmonization and standardization, and multiregional data workflow.
The RePORT Brazil and related RePORT South Africa concepts were presented together. The research areas, funding acquired and samples of the publications arising from these RePORT cohorts were summarized. The purpose of these networks is to bilaterally fund RePORT networks or continue to fund them in Brazil and South Africa to help facilitate development of tools to improve treatment outcomes for adults and pediatric populations at the individual level and to inform strategies to curtail the TB and HIV epidemics at the population level, regionally and globally.
The joint research priorities for both of these networks were developed in collaboration with the countries’ respective health research council or health ministry. The reviewers’ comments and suggestions for all of three initiatives were summarized and responses to them were addressed.
Discussion: None
Ballot Voting Outcome:
12 Approval
0 Approval with modification(s)
0 Deferral for further information
0 Disapproval
Prevention Sciences Program
Biomarker Signatures of TB Infections in Young Children With and Without HIV
Patrick Jean-Philippe, M.D.
The purpose of this new initiative is to advance research to discover and validate novel biomarkers of TB infection and subsequent risk of progression to TB disease in young children living with and without HIV. There is a high global TB burden in children with 67 million prevalent and 15 million incident TB infections. Also, there is a high TB case detection gap, and a high risk of disease progression following exposure in children. Diagnosis remains challenging for those who progress making preventative approaches critical for improving health outcomes. There is a TB prevention gap as evidenced by the high proportion of TB infection and disease in children without TB exposure history, sub-optimal tests for TB and a majority of children with known TB contacts receive no screenings. Current preventive treatments are effective but they are limited by side effects or duration and adherence challenges that result in decreased completion rates.
The scope of this initiative seeks to support the discovery and validation work specific to this young age group, for biomarkers that can 1) identify children with TB infection and discriminate between those who do and don’t progress to active disease, allowing targeted treatment to those at risk of progression, and 2) enable potential translation to simple, rapid, inexpensive, hand-held point-of-care-based tools for use by minimally-trained health workers, within/outside contact tracing settings. This initiative is built on and complements other related programs but is not focused on assay/technology development for a point-of-care test.
The reviewers’ comments and suggestions for this initiative were summarized and responses to them were addressed.
Discussion: None
Ballot Voting Outcome:
12 Approval
0 Approval with modification(s)
0 Deferral for further information
0 Disapproval
Resources to Advance Pediatrics and HIV Prevention Science (RAPPS)
James Cummins Jr., Ph.D.
This contract is a third iteration of previous contracts and will be for seven years. The purpose of this new iteration will be to provide drug development resources to support advancement of the next generation of HIV biomedical prevention products, as well as HIV treatment and prevention strategies in maternal and pediatric populations. The three primary objectives of the program are:
- To advance the most promising next generation non-vaccine HIV biomedical prevention products into human clinical testing
- To expand marketing science and user preference studies to better understand desire and choice and how best to engage women and men in HIV prevention (emphasis on adolescent girls and young women ages 14 to 25 years old)
- The provision of gap-filling resources to support HIV prevention and treatment strategies in maternal and pediatric/adolescent populations
The scope of the contract includes product development resources to advance next generation HIV biomedical prevention products and HIV treatment and prevention strategies in maternal and pediatric populations through gap-filling contract resources that support licensure of HIV prevention products, enable industrial partner clinical testing, and enhance development of age-appropriate pediatric, adolescent, and adult formulations.
A history of previous versions of the RAPPS contract (Comprehensive Resources for HIV Microbicides and Biomedical Prevention (CRMP) contracts) was summarized and outcomes from these were listed. Changes in RAPPS from the previous CRMP contracts were outlined and discussed and a roadmap for the development of a pediatric formulation was presented. The development and leveraging of relationships with groups and pharmaceutical companies and identification of opportunities were important aspects needed for this contract.
The reviewers were supportive and expressed enthusiasm for this initiative. Their comments and suggestions for this initiative were summarized and responses to them were addressed.
Discussion:
Q1: You have an age group that's 18 to 24. Does the MTN not do any of this? Do you need a special subgroup to look at this?
A: There are groups like MTN conducting studies such as these, the focus is typically a little different since there may be a clinical trial setting or based on clinical sites. We engaged the School of Business at the University of Maryland for the marketing studies. That's very different from your traditional behavioral type studies. It is trying to get inside the heads of these at-risk populations and really understand what drives their decision making.
Q2: Has the marketing group engaged with young people from this age group to inform their marketing?
A: Yes, we're using a company that's very experienced and working with this population in South Africa.
Ballot Voting Outcome:
11 Approval*
0 Approval with modification(s)
0 Deferral for further information
0 Disapproval
*Dr. Agarwal recusal, member in conflict
Public Comments: None
VII. Adjournment
The meeting of the Council adjourned at 3:26 p.m., on Monday, June 7, 2021.
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.