NIAID Council Minutes June 6, 2022

The 201^st meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened virtually at 10:30 a.m. on Monday, June 6, 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 12:02 p.m. and from 1:00 p.m. to 3:58 p.m. The meeting was closed to the public from 8:30 a.m. to 10:30 a.m. and from 12:05 p.m. to 12:15 p.m. for review and consideration of individual grant applications. Notice of the meeting was published in the Federal Register.

Meeting Attendees

Table of Contents

I. Review of Grant Applications
II. Remarks of the Director, NIAID—Anthony S. Fauci, M.D.
III. Guest Speaker—Richard Koup, M.D., Acting Director, Vaccine Research Center
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 4,802 research and training applications with primary assignment to NIAID for a requested amount of $2,084,870,498 in first-year direct costs and recommended approval of 2,447 applications with $1,122,227,353 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 also introduced three ad hoc members: Dr. James Gern, Chief of the Division of Allergy, Immunology, and Rheumatology and Vice Chair of Research in the Department of Pediatrics at the University of Wisconsin School of Medicine and Public Health; Dr. Carole Ober, the Blum-Riese Distinguished Service Professor in the Department of Human Genetics at the University of Chicago; and Dr. Matthew Altman, Associate Professor in the Department of Medicine, Division of Allergy and Infectious Diseases, Head of the Allergy Section, and Associate Scientist at the Benaroya Research Institute at the Virginia Mason Medical Center in Seattle. 

Consideration of Minutes of Previous Meeting

Council considered the minutes of the January 31, 2022 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.

On February 18, the Senate confirmed Dr. Robert Califf as FDA Commissioner. 

Dr. Ashish Jha replaced Jeff Zients as the White House COVID-19 Response Coordinator.

HHS Secretary Xavier Becerra announced the formal establishment of the Advanced Research Project Agency for Health, or ARPA-H, as an independent entity within NIH. Dr. Adam Russell has been named Acting Deputy Director.

In April, Dr. Ned Sharpless stepped down as Director of the National Cancer Institute (NCI). NCI Principal Deputy Director Dr. Doug Lowy will serve as NCI’s Acting Director until a new director is selected.

Vaccine Research Center (VRC) Director Dr. John Mascola retired in April. Dr. Richard Koup is serving as VRC Acting Director while a search for a permanent director is being conducted. 

Dr. Julie Ledergwood, VRC Deputy Director and Chief Medical Officer, also departed VRC. Dr. Karin Bok is VRC’s Acting Deputy Director, and Dr. Bob Seder is VRC’s Acting Chief Medical Officer and Acting Associate Director.

Marie Parker has been named NIAID Associate Director for Science Management. She also serves as the Deputy Executive Officer for NIAID.

Dr. Jane Knisely joined NIAID’s Immediate Office of the Director (OD) as Special Assistant for Scientific Projects and is helping coordinate various aspects of NIAID’s response to the COVID-19 pandemic. Dr. Ian Simon also joined the Immediate OD as a Senior Advisor providing advice and expert analysis on issues related to emerging infectious diseases and pandemic preparedness planning and management. 

In the Division of Extramural Activities (DEA), Dr. Kelly Poe has been appointed Deputy Director, Dr. Jennifer Meyers has been named the new Deputy Director for the Scientific Review Program (SRP), and Dr. Priti Mehrotra is the new Branch Chief of the Microbiology Review Branch - A in SRP.

Dr. Sonja Best has been selected as Chief of the Laboratory of Persistent Viral Diseases at Rocky Mountain Laboratories.

Dr. Tedros Adhanom Ghebreyesus was re-elected Director-General of the World Health Organization.

Meetings and Events

Dr. Fauci reported on virtual and in-person meetings that have been held with international delegations and health officials. He met virtually several times with the United Kingdom’s Chief Medical Officer Professor Christopher Whitty and Chief Scientific Officer Sir Patrick Vallance.

In February, Dr. Fauci met with Alfredo Borrero, Vice President of Ecuador, and Ximena Garzón-Villalba, Ecuadorian Minister of Public Health, to discuss the current COVID-19 situation in Ecuador and South America. 

In April, Dr. Fauci and leaders from several NIAID divisions met with leadership of the Korea National Institute of Infectious Diseases to sign a letter of intent to enhance cooperation with South Korea on immunology and infectious diseases research. 

In May, Dr. Fauci met with Roberto Speranza, the Italian Minister of Health, to discuss COVID-19, Italy’s plans for a National Center for Pandemic Preparedness, and areas for potential collaboration.

The founder and chairman of the Serum Institute of India, Dr. Cyrus Poonawalla, and his son Adar C. Poonawalla, the Institute’s CEO, met with Dr. Fauci in late May to discuss dengue vaccines, TB vaccines, malaria research, mRNA vaccines, monoclonal antibodies, and adjuvant research.

Budget Update

Dr. Fauci began by comparing the fiscal year (FY) 2022 enacted budget with the FY 2021 enacted budget. NIH received an overall increase of 7.5 percent. NIAID received a 4.2 percent increase, for a total of $6.322 billion.

On March 28, President Biden released his FY 2023 budget request, which includes an overall increase of 9.3 percent for NIH, or $4.3 billion above the FY 2022 enacted level. The President’s Budget also requests $4 billion for ARPA-H to develop state-of-the-art tools and technologies that will drive transformational innovation in health research and speed application and implementation of health breakthroughs. The initial focus areas of ARPA-H will include diseases such as cancer, diabetes, and Alzheimer’s.

Dr. Fauci summarized NIAID’s FY 2022 financial management plan. Our R01 payline is set at the 12 percentile for established principal investigators (PIs) and the 16 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 18 to 22 percent.

Dr. Fauci highlighted research areas that Congress has earmarked for NIAID to spend allocated budget amounts, including support for Ending the HIV Epidemic in the United States; developing universal influenza vaccines; Lyme and tick-borne diseases research; antimicrobial resistance research; Consortium of Food Allergy Research; Regional Biocontainment Laboratories to continue efforts to prevent, prepare for, and respond to infectious disease outbreaks; and SARS-CoV-2 immunity profiling.

He provided an update on the COVID-19 funding NIAID received as well as how the Institute has allocated the funds.

Legislative Update

On May 11, Dr. Fauci accompanied Acting NIH Director Dr. Lawrence Tabak, along with several other NIH institute directors, to a hearing of the House Appropriations Labor-HHS Subcommittee on the President’s FY 2023 NIH Budget Request. Dr. Fauci provided updates on NIAID’s Pandemic Preparedness Plan, as well as ongoing research to better understand and treat COVID-19, develop universal influenza vaccines, and advance our understanding of the advantages of and potential barriers to xenotransplantation.

On May 17, Dr. Fauci and Dr. Tabak attending a hearing of the Senate Appropriations Labor-HHS Subcommittee on the President’s FY 2023 NIH Budget Request. Topics covered included COVID-19, NIH efforts to better understand and treat long COVID, and the need to develop candidate therapeutics and vaccines for viral families of concern in preparation for the next pandemic threat.

Dr. Fauci participated in numerous briefings with members of the Senate and House of Representatives that focused on COVID-19 and research on universal influenza vaccines.

On February 24, Dr. Fauci participated in the annual Dominicans on the Hill event, which provided an opportunity to discuss the importance of COVID-19 vaccination, issues around vaccine hesitancy, and the ongoing COVID-19 pandemic. 

Dr. Fauci thanked NIAID staff who participated in many briefings and events on his behalf.

Other Information Items

Dr. Fauci began by explaining NIAID’s research has a dual mandate—to maintain and grow a robust basic and applied research portfolio in microbiology, infectious diseases, immunology, and immune-mediated diseases, while also being able to respond rapidly to emerging and re-emerging disease threats. He then noted several infectious disease outbreaks that have occurred in 2022, including monkeypox, COVID-19, acute hepatitis of unknown etiology in children, Ebola, and Avian influenza A.

He mentioned NIAID’s Pandemic Preparedness Plan, which targets prototype and priority pathogens and takes a preemptive approach designed to identify viral threats before they emerge. NIAID has also established an Antiviral Program for Pandemics to develop new medicines to combat COVID-19 and prepare for other pandemic threats. The Institute recently awarded nine Antiviral Drug Discovery Centers for Pathogens of Pandemic Concern.

Dr. Fauci continued with an update on the recent monkeypox outbreak in non-endemic countries, including number of confirmed cases, countries with the most cases, available countermeasures, and a summary of NIAID’s monkeypox research.

Next, he provided an update on COVID-19, summarizing the number of COVID-19 cases and deaths globally and in the United States, evolving variants with greater transmissibility, vaccines available, recommendations for booster shots to counter waning immune protection, and current therapeutics.

Dr. Fauci concluded with an update on HIV/AIDS, reporting on PEPFAR outcomes and noting that Dr. John Nkengasong has been appointed the new U.S. Global AIDS Coordinator for PEPFAR. NIH launched a clinical trial of three experimental HIV mRNA vaccines to examine safety and the ability to induce an immune response. FDA approved Cabenuva, the first extended-release, injectable drug regimen for adults living with HIV, which is administered by injection once every four weeks.

III. Guest Speaker—Richard Koup, M.D., Acting Director, Vaccine Research Center

Dr. Richard Koup began with a brief overview of the VRC, which was established in 2000 as a Center dedicated to research and development of HIV vaccines. In the 21 years since it was established, the scope of the Center has significantly expanded. VRC has an integrated team of scientists, which includes experts in immunology, virology, structural biology, bioengineering, product formulation, manufacturing, and clinical trials.

VRC has unique facilities and capabilities that allow it to translate basic scientific discoveries into manufacturing of clinical grade materials for use in first-in-human clinical trials. Since VRC cannot license products for clinical use, it then partners with industry to take the products through full development and licensure.

Dr. Koup continued by summarizing VRC’s contributions to the national effort to develop, test, and demonstrate efficacy of COVID-19 vaccines, and collaborations with AbCellera and Eli Lilly on the discovery and development of COVID-19 monoclonal antibodies.

He highlighted VRC’s research efforts on universal influenza vaccines, which includes nanoparticle-based vaccine platforms for influenza and structure-based stabilization of influenza neuraminidase tetramers. 

Dr. Koup concluded with an update on VRC’s approach to pandemic preparedness and strategy to prepare for potential future viral pandemics and described work using fusion protein engineering and immunological surveillance. 

IV. Report of the Allergy, Immunology, and Transplantation Subcommittee–Daniel Rotrosen, M.D., Director, DAIT

Dr. Rotrosen welcomed the subcommittee members to the 201^st meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting.

Dr. Rotrosen presented the following scientific and Division activities:

Staff and Organizational Changes

Rija John, R.N., M.S.N., Ms. John joined the Autoimmunity and Mucosal Immunology Branch as a Nurse Consultant/Project Manager in January 2022. She received her Master’s in Nursing Education from Grand Canyon University, Arizona. Prior to joining NIAID, she was a research nurse specialist at the Office of Research Support and Compliance at the NIH Clinical Center. She has extensive experience in various therapeutic areas and in all phases of drug and device trials.

Deborah L. Hodge, Ph.D., Dr. Deborah Hodge joined the Autoimmunity and Mucosal Immunology Branch as a Program Officer in April 2022. Dr. Hodge joined NIH in 2002 and has worked in research and research administration positions, most recently for 8 years as a Scientific Review Officer and Referral Officer at the NIH Center for Scientific Review. Dr. Hodge received her Ph.D. in biochemistry from West Virginia University and her Bachelor of Science from Shepherd College. 

Selected Funding Opportunities

NIAID

Request for Information (RFI): Sex Differences in Radiation Research: Animal Models, Underlying Pathways, Biomarkers of Injury, and Medical Countermeasure Responses NOT-AI-22-040: The purpose of this RFI is to solicit information from the radiation research community to provide input on how sex differences in radiation responses influence: 1) radiation-induced injuries in preclinical animal models, 2) efficacy of medical countermeasures (MCMs), and/or 3) evolution of biomarkers (for biodosimetry development). The goal of this RFI is to gain insight into the current research landscape on sex differences in radiation injury, and specifically to learn about the challenges and gaps in the field.

Immune Drivers of Autoimmune Disease, RFA-AI-22-012: The purpose of this funding opportunity is to 1) improve our understanding of the immunologic processes and events that drive not only the course of autoimmune disease but also the preclinical phase and the transition from subclinical autoimmunity to diagnosed autoimmune disease and 2) establish innovative approaches that will facilitate further studies by enhancing feasibility of large-scale studies and reducing both financial costs and the burden to subjects. It is anticipated that three or four awards will be made. Applications are due July 1, 2022.

Notice of Special Interest (NOSI): Optimizing Vascularized Composite Allograft Survival NOT-AI-22-023: This NOSI encourages submission of R01 and R21 applications (clinical trial not allowed) that utilize animal models or human tissue specimens to 1) understand immune mechanisms of rejection and tolerance and/or 2) develop therapeutic and monitoring approaches applicable to face, limb, and abdominal wall vascularized composite allograft (VCA) transplantation. The overarching goal is to expand clinical opportunities and improve outcomes for these life-enhancing procedures by reducing incidence of acute rejection, maximizing graft survival, and minimizing the immunosuppression required for long-term VCA acceptance.

Request for Applications (RFA): Nonhuman Primate Transplantation Tolerance Cooperative Study Group (Clinical Trial Not Allowed) RFA-AI-22-002 (U01) and RFA-AI-22-003 (U19): These RFAs solicited applications for a multi-center, cooperative program dedicated to developing, optimizing, and evaluating approaches to induce and maintain immune tolerance to allogeneic transplants in nonhuman primate models. The over-arching goal is to facilitate clinical translation of safe and effective tolerance-induction protocols for long-term graft survival.

Division Activities

Allergy, Asthma, and Airway Biology Branch

SARS-CoV-2 and Atopy: Results from NIAID-Sponsored Studies. On May 16, 2022, as part of the annual meeting of the American Thoracic Society (ATS), NIAID organized a session entitled “SARS-CoV-2 and Atopy: Results from NIAID-sponsored Studies.” The session described results from three NIAID-sponsored studies developed to address public health issues during the COVID-19 pandemic: 1) the HEROS study, reporting on risk factors for SARS-CoV-2 infection and household transmission in allergic and non-allergic individuals, 2) the SARS Vaccination trial, which is assessing the risks associated with mRNA vaccine administration in individuals with atopy, and 3) the IMPACC COVID-19 cohort study, reporting on the association of Type 2 endotype with the severity of illness in these patients.

Findings from the Mechanisms Underlying Asthma Exacerbations Prevented and Persistent with Immune-Based Therapy: A system Approach Phase 2 (MUPPITS-2). On May 18, 2022, as part of the annual meeting of the American Thoracic Society (ATS), NIAID organized a session entitled “Findings from the Mechanisms Underlying Asthma Exacerbations Prevented and Persistent with Immune-Based Therapy: A system Approach Phase 2 (MUPPITS-2).” The session highlighted new work performed by investigators from the NIAID-funded Inner City Asthma Consortium (ICAC) and Childhood Asthma in Urban Settings (CAUSE) network. Three investigators presented the findings from the MUPPITS-2 randomized double-blind clinical trial, which is studying the efficacy of mepolizumab in moderate to severe eosinophilic asthma. In addition to clinical findings, nasal transcriptomic heterogeneity and its relation to clinical diseases were discussed, and the role of eosinophil surface markers to distinguish clinical disease phenotypes was presented.

SID-NIAID Symposium: Atopic Dermatitis Research Updates. On May 19, 2022, NIAID organized a symposium presentation at the annual Society for Investigative Dermatology (SID) meeting. Four experts in the field discussed the identification of atopic dermatitis (AD) endotypes and phenotypes, the identification of genes that regulate filaggrin expression in human skin, the impact of IL-4Ra blockage (e.g., dupilumab) on the host-microbe interface in AD, and the role of targeted bacteriotherapy to address S. aureus colonization as a new treatment for AD.

Basic Immunology Branch

Innate Immunity During SARS-CoV-2 Infection and COVID-19 Workshop. On January 4 and 5, 2022, BIB hosted a virtual workshop that was co-chaired by Drs. Ralph Baric, John Lambris, and Jenny Ting. During the workshop, experts in the innate immunity and virology fields presented and discussed current research findings in the rapidly evolving field of host innate immune responses to SARS-CoV-2 and the role of innate immunity in the development of COVID-19. The speakers also discussed potential innate immune components as therapeutics targets and the gaps in knowledge regarding the contribution of innate immune factors regulating host responses to SARS-CoV-2. Nature Reviews of Immunology journal will publish a viewpoint article based on the discussions at the workshop shortly.

Maintaining Immunity After Immunization Annual Meeting. On February 7, 2022, the annual progress update was held as a virtual teleconference. The Maintaining Immunity after Immunization program supports projects that seek to define the components and mechanisms of the immune response essential for induction of persistent or life-long protective immunity following vaccination. This meeting provided a venue for the project investigators to give an update on progress and to develop scientific collaborations with each other to foster program success.

Joint Annual Adjuvant Discovery and Development Program Meeting. On June 1 and 2, 2022, in Rockville, Maryland, a joint meeting was held for the NIAID Adjuvant Discovery and Development contract programs. The NIAID Adjuvant Discovery program supports the discovery of novel vaccine adjuvants that can be used to improve vaccine efficacy and durability, while maintaining safety. The goal of the Adjuvant Development program is to establish and expand the availability of novel vaccine adjuvants that researchers can use for vaccine development. It supports the preclinical development of novel vaccine adjuvants towards licensure for human use. Twelve contractors, six from each of the Discovery and Development programs, provided updates on progress made in the past year and plans for the coming year. The meeting also provided a venue for contractors to exchange information and ideas, foster collaborations, and leverage resources and expertise in the field.

NIAID Guest Symposium at Immunology 2022 (AAI Annual Meeting): Computational Modeling: Novel Insights into Immunity to Infections or Vaccines. On May 9, 2022, an NIAID-led symposium on computational modeling was held with three invited speakers from the NIAID Computational Immunology Program and a speaker from the Adjuvant Discovery program. Computational immunology allows for a deeper understanding of the dynamics of complex host immune responses triggered in infectious or immune-mediated diseases and can be particularly important for newly emerging diseases such as COVID-19. This symposium emphasized research that integrates experimental immunology and computational modeling to define host responses triggered by infectious pathogens or vaccines against them, and development of novel vaccine adjuvants.

Cohort Studies to Improve Our Understanding of Influenza Immunity, Vaccine Response, and Effectiveness in Older Adults. On May 11, 2022, the kick-off meeting was held via a virtual platform for the new program to understand influenza immunity, vaccine response, and effectiveness in older adults. This is a partnership between DAIT and the NIAID Division of Microbiology and Infectious Diseases (DMID). Based on characterization of existing or new longitudinal cohorts, the goal of the program is to determine how changes in immune function in individuals 65 years of age and older, including the role of pre-existing immunity to influenza generated by a history of natural infections and/or vaccinations, impact protective immunity. Three awards were made under this initiative to the Jackson Laboratory (Duygu Ucar and George Kuchel), the Dana-Farber Cancer Institute (Wayne Marasco), and Johns Hopkins University (Sean Leng). Awardees presented their research plans and preliminary findings from each of their cohorts. The meeting provided a forum for researchers to exchange ideas and to begin discussions for future collaborations.

Transplantation Branch

HLA and KIR Region Genomics in Immune-Mediated Diseases. On April 28, 2022, the Steering Committee meeting for this 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. The current consortium is evaluating immunogenetic associations with 1) asthma, 2) CNS paraneoplastic syndromes, 3) graft failure following hematopoietic cell transplantation, 4) primary nephrotic syndrome, including its recurrence post kidney transplant, and 5) clinical outcomes following heart, kidney, liver, and lung transplantation. The program continues to support the generation of high quality, publicly accessible HLA- and KIR- genomic data sets and associated phenotypic data. The meeting, attended by Consortium members and extramural staff from NIAID and co-funding institutes, National Cancer Institute and National Institute of Neurological Disorders and Stroke, included presentations on project progress to date. Following the presentations, the consortium discussed areas of synergy, the availability of and limitations in analytical tools for immunogenetics, and data sharing methods.

Autoimmunity and Mucosal Immunology Branch

Cooperative Study Group for Autoimmune Disease Prevention. On February 15, 2022, the annual meeting of the Cooperative Study Group for Autoimmune Disease Prevention was held by videoconference. The mission of this program is to engage in scientific discovery that significantly advances knowledge for the prevention and regulation of autoimmune disease. During the meeting, the group’s principal investigators and their co-investigators presented recent highlights from their projects in type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. The group also heard and discussed reports from investigators who were awarded funding from the CSGADP for pilot studies related to autoimmune disease prevention and discussed potential opportunities for future collaborations.

Mucosal Immunology Studies Team (MIST). On April 4, 2022, the first annual meeting of the second round of the MIST cooperative agreement research program was held as a virtual meeting. MIST is composed of eleven U01 cooperative agreement awardees who focus on discovery of novel immune mechanisms, cells, mediators, and pathways operating at the mucosal surface; exploration of innovative hypotheses; and tackling difficult unsolved questions in mucosal immunity. The MIST awardees presented their awarded projects, provided constructive advice on these projects, shared ideas and newly developed tools that could be useful in the study of mucosal immunity, and discussed ideas for optimal use of MIST pilot project funds. (https://www.mucosal.org/)

Radiation and Nuclear Countermeasures Program (RNCP)

NIAID/BARDA Inter-Agency Update Meetings. On April 1, 2021, RNCP staff met with Biomedical Advanced Research and Development Authority (BARDA) program managers responsible for biodosimetry development at the Agency. The purpose of these biannual meetings (held regularly since 2014 and requested by the HHS Assistant Secretary of Preparedness and Response) is 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 for each program.

2022 Sex Differences in Radiation Research Workshop. On April 26 and 27, 2022, a virtual workshop was held to understand how sex differences can affect animal models and medical countermeasure (MCM) development. In addition, the effects of sex differences on the development of biodosimetry and/or biomarkers used to assess acute radiation syndrome (ARS), delayed effects of acute radiation exposure (DEARE), and/or predict major organ morbidities also were examined. Discussions included challenges in medical research lacking representation from both sexes and regulatory policies that influence inclusion of women in research. To emphasize the importance of this topic, real-world sex differences in human health scenarios also were explored. This workshop discussed the current state of the field, identified research gaps, and helped to formulate a strategic plan for future activities. The workshop was well attended (>180 attendees) and a meeting report will be published in a peer-reviewed journal.

2022 Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures Workshop. On January 13 and 14, 2022, a virtual workshop brought together experts from two distinct fields, radiation and sulfur mustard, to share ideas on commonalities between these research fields, with the goal of identifying new areas for drug and treatment discovery. NIAID and BARDA program staff planned the workshop, which included speaker sessions on organ systems impacted by these insults and their mechanisms of action. In addition, a session dedicated to regulatory issues was included with speakers from industry partners (Amgen and Argentum Medical) and staff from FDA. Publication of a comprehensive meeting report is planned.

U01 Novel Bioassay and Biodosimetry Devices Annual PIs Meeting. On March 2, 2022, the RNCP conducted a virtual annual meeting for the U01 consortium “Novel Bioassays and Biodosimetry Devices.” The objectives of the meeting were to 1) provide a forum that allowed for creative interactions between investigators and 2) enable the investigators to share the background on their planned projects and progress over the past year. 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 staff, and other U.S. government agencies. Plans were elaborated for awardees to request informal interactions with the FDA and to focus on key developmental issues for the upcoming year.

FY 2024 Research Concept Clearances Presented to Division Advisory Council

The subcommittee endorsed and unanimously approved the following four Research Concept Clearances:

Cooperative Centers on Human Immunology (U19, Clinical Trial Optional)
The primary objectives of this program are to discover new principles of human immunology, support technology development to advance studies of the human immune system, and advance hypothesis-driven research on the human immune system, leading to discovery of novel pathways of immune response and regulation relevant to the prevention and treatment of infectious disease, as well as immune-mediated diseases. Secondary objectives include 1) supporting the centralized infrastructure needed to coordinate multi-disciplinary research in human immunology, and 2) promoting public data access, the continued recruitment of outstanding immunologists to the study of the human immune system, and the flexibility to support new research opportunities as they arise.

Immunity in Older Adults (R01, Clinical Trial Not Allowed)
The objective of the program is to expand understanding of the changes that occur in immune function during the aging process that contribute to impaired responses to pathogens and vaccines.

Maintaining Immunity after Vaccination and Infection (U01, Clinical Trial Not Allowed)
This initiative will focus on determining the immune mechanisms that lead to sustained immunity and how they differ amongst various vaccines and/or pathogenic infections. Projects will address what particular components of the immune response are stimulated, how effectively they are stimulated, and how effective immune responses persist.

Autoimmunity Centers of Excellence, Basic Component (U19, Clinical Trial Not Allowed)/ Autoimmunity Centers of Excellence, Clinical Component (UM1, Clinical Trial Required)
The Autoimmunity Centers of Excellence (ACE) program will continue to perform multidisciplinary, collaborative research investigations focused on the basic mechanisms of autoimmunity, self-tolerance, and immune modulation in autoimmune diseases. The ACE implements clinical trials testing novel immunotherapies for autoimmune diseases with integrated mechanistic studies. The program is not restricted to particular autoimmune diseases. Applications studying more than one disease are encouraged.

V. Report of the Microbiology and Infectious Diseases Subcommittee–Emily Erbelding, M.D., M.P.H., Director, DMID

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 6, 2022. She provided a DMID personnel update, recognizing new staff appointments made in the Division since the last Council meeting, including Nadine Bowden and Kyung Moon in the Bacteriology and Mycology Branch; Candace Kerr and Caitlyn Cabral in the Office of Biodefense, Research Resources and Translational Research (OBRRTR); Meenu Upadhyay in the Respiratory Diseases Branch; and Andrew Burnham in the Office of Clinical Research Resources..

Following staff introductions, Dr. Erbelding provided a report on recent DMID activities of note:

• Dr. John Beigel, DMID Associate Director for Clinical Research, received the Department of Health and Human Services Secretary’s Award for Distinguished Service in recognition of his efforts to design and implement clinical trials to evaluate potential treatments and an investigative vaccine against the SARS-CoV-2 virus.
• The drug Baricitinib, which was evaluated through the NIAID Adaptive COVID-19 Treatment Trial, was approved by the FDA for treatment of hospitalized patients with COVID-19.
• DMID awarded nine new Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern, which will conduct innovative, multidisciplinary research to develop candidate COVID-19 antivirals, especially those that can be taken in an outpatient setting, as well as antivirals targeting specific viral families with high potential to cause a pandemic in the future.
• DMID recently launched the COVID Variant Immunologic Landscape Trial, a Phase 2 clinical trial that will evaluate various additional COVID-19 booster shots.
• The SARS-CoV-2 Assessment of Viral Evolution (SAVE) program continues to provide a comprehensive real-time risk assessment of emerging changes in the virus that could impact transmissibility, virulence, susceptibility to convalescent and vaccine-induced immunity and diagnostic testing. The program provides important information for variant characterization and complements other USG and NIH efforts.
• DMID established the Tuberculosis Research Advancement Centers (TRACs) in response to a recent targeted funding opportunity announcement. The centers will support the development of a next generation of tuberculosis (TB) researchers by providing focused mentoring and funding support for new investigators.
• Preliminary results of a NIAID-supported study found that a significant proportion of bacterial STIs (gonorrhea, chlamydia, or syphilis) were prevented by prophylactic treatment with a dose of doxycycline after unprotected sex. Further study data will be shared and discussed at the 2022 International AIDS Conference.
• DMID-supported activities to address the current Monkeypox epidemic were briefly summarized. NIAID played a key role in the development of the JYNNEOS vaccine, which is currently available to prevent monkeypox virus disease, as well as antiviral treatments for smallpox that may also be used for monkeypox. It was noted that DMID will collaborate with CDC on a serologic “look back” exercise focused on disease transmission in the United States.

FY 2024 Concepts Presented for Clearance

The following concepts were presented to the Subcommittee. All concepts were approved.

International Centers of Excellence for Malaria Research (ICEMR) – this concept will support multidisciplinary research that integrates clinical and field aspects with laboratory, molecular, and genomic methods to inform malaria intervention, control, and prevention programs. The Subcommittee commended DMID on the outstanding accomplishments of the ICEMR program. One Subcommittee member suggested that ICEMR grantees should collaborate and share data among themselves and potentially with other programs [e.g., the DAIT-supported Human Immunology Project Consortium (HIPC), which shares data through ImmPort]. The Subcommittee supported the idea of the ICEMRs conducting translational research, including product testing and evaluation. Subcommittee members appreciated the contribution of the endemic countries’ resources in supporting the research efforts of the ICEMRs, as well as the importance of supporting collaborative research efforts in diverse global settings. Overall, the Subcommittee recognized the value of the ICEMRs to the scientific and global health communities, agreed that the ICEMR network is a critical component of NIAID’s Global Health Research Program, and enthusiastically supported renewal of the ICEMRs.

DMID Clinical Research Operations & Management Support (CROMS) – this concept will support a host of activities critical to ensuring that NIAID’s clinical research is conducted and overseen in a way that meets U.S. regulations and NIH policies, while allowing the data to be used to advance science, inform public policy, and support regulatory decisions. The DMID Subcommittee recognized the critical nature of the CROMS program in fulfilling DMID’s regulatory obligations, ensuring high quality clinical trial data, and protecting research participants. The Subcommittee noted the magnitude of the CROMS program, spanning a broad range of infectious diseases and interventions. They also complimented the support that CROMS has provided, serving as a resource for the clinical research community through the dissemination of best practices and training related to the conduct of clinical trials.

Genetic Tools for Understanding Rickettsial and Related Infections – the objective of this concept is to develop or optimize strategies for genetically manipulating human pathogenic Rickettsia, Ehrlichia, Anaplasma, and Orientia species. The most promising projects will then be tasked with applying these tools to the generation of mutant strain libraries for use by the entire rickettsiales research community. The Subcommittee recognized the importance of rickettsial diseases in the global health arena, as well as their role as tick-borne infections in the United States and elsewhere. As presented by program staff, research on pathogens within the order Rickettsiales—such as Rickettsia, Ehrlichia, Anaplasma, and Orientia species—has long been hindered by a lack of suitable genetic tools. For these pathogens, their obligate intracellular lifecycle has produced barriers to genetic manipulation and a subsequent lack of tools that has frustrated attempts to better understand their fundamental biology, pathogenesis, transmission, and host response. Subcommittee members recognized that despite isolated successes in genetic modification of models, and utilize these models to identify the most promising combination regimens for clinical testing. The DMID Subcommittee recognized the importance of TB therapeutics research and the new concept for rational design of new TB regimens. Despite campaigns to eradicate TB, mass treatment with three individual species, the field still lacks the facile, standard approaches or large libraries of mutant strains required to expand our knowledge of rickettsial diseases in humans. Subcommittee members agreed that a targeted initiative was needed to address this problem and that a two-phase approach would best enable success. One member also noted that, given the tendency of rickettsial pathogens to target host endothelia, improved research on these bacteria may have spillover to our understanding of other diseases such as COVID.

Consortium for Design of TB Drug Regimens – this concept would establish a consortium of tuberculosis (TB) preclinical and clinical experts to analyze relevant pre-clinical and clinical data, systematically refine preclinical to four drug regimens given daily for months has resulted in the emergence of drug resistance. More potent, shorter, and safer strategies are needed to effectively treat individuals across the life span, interrupt person-to-person transmission, and ultimately eradicate TB. Infected mouse disease models have successfully driven strategies for recent Phase 1 and 2 clinical trials of single drugs demonstrating safety and decreasing bacterial burden but have had limited success with predicting Phase 3 trial outcomes with combination treatments. Staff pointed out that with a large number of new candidate compounds described in the literature and more than 15 new chemical entities in early clinical stages, combination regimens will require careful evaluation before expensive Phase 2/3 clinical trials can begin. The Subcommittee agreed that the concept was a sensible approach to a complicated problem.

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 unanimously approved the summary minutes of the January 31, 2022 meeting.

Director’s Report

Carl Dieffenbach, Ph.D.

Dr. Dieffenbach welcomed Jonah B. Sacha, Ph.D., to the ARAC as the new Office of AIDS Research Advisory Council (OARAC) Liaison to the ARAC.

Budget Update

NIAID received a 4.2 percent budget increase in FY 2022 as enacted.

The FY 2023 President’s budget request showed a projected decrease of 0.9 percent which was explained by the fact that the budget was built prior to the approval of the final FY 2022 budget.

NIAID FY 2022 Financial Management Plan

Key points:

• R01 paylines for established PIs is the 12th percentile and for new PIs is the 16th percentile.
• No adjustments to noncompeting or competing grants.
• Competing research initiatives cut up to 20 percent.
• Estimated success rates: 18 to 22 percent.

The increase in Congressional directives (earmarks) was summarized in a list.

Scientific and Programmatic Updates

NIH Priorities for HIV and HIV-Related Research
The top priorities focus on reducing the incidence of HIV, research towards an HIV cure, next generation HIV therapies, co-infections, comorbidities and complications, and cross-cutting areas.

NIAID HIV/AIDS Strategic Goals
NIH and NIAID strategic goals are aligned with the National HIV AIDS Strategy and are focused on addressing the Ending the HIV Epidemic initiative. We seek to achieve our goals through establishment of strategic partnerships within NIH, HHS and USG as well as with other governments and outside groups such as Pharma, the Gates Foundation, and the International AIDS Vaccine Initiative. A key principle is consultation with community, and the activities are evaluated through the lens of diversity, equity, inclusion, and accessibility.

NIAID Civility and Diversity Updates

• Establishment of a workplace civility taskforce was to provide input on and champion workplace civility and anti-harassment efforts across the Institute.
• Establishment of a Diversity, Equity, Inclusion, and Accessibility (DEIA) Council to help NIAID plan to address DEIA, including the internal and the extramural research workforces, and in research to address health disparities.
• Plans for development of a new cross-NIAID funding opportunity announcement (FOA) that will be presented for approval this afternoon: NIAID Research Opportunities for New and "At-Risk" Investigators to Promote Workforce Diversity.
• Civility was defined as an expectation statement: To create a civil workplace, NIAID expects all staff, regardless of background or position, to act with professionalism and respect, listen with an open mind, communicate constructively, and work collaboratively in support of the NIAID mission.
• A civility pledge that was developed for employees/by employees was shared.
• A statement regarding the DEIA Council was presented. Two workgroups of the DEIA Council have been formed to help it become actionable.

The Plan for Enhancing Diverse Perspectives (PEDP) – a BRAIN Diversity Initiative
This plan was summarized and viewed as another approach that could be adapted by NIAID. NIAID is going to pilot this type of an approach for FOAs. Some of the goals to be described in the plan include:

• Maximize participation of investigators from diverse backgrounds, including groups traditionally underrepresented in the biomedical, behavioral, and clinical research workforce, such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Engage with different types of institutions and organizations (e.g., research-intensive and research active, undergraduate-focused, minority-serving, community-based).
• Use project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse early- and mid-career researchers.
• Create training and mentoring opportunities encouraging participation of students, postdoctoral researchers, and co-investigators from diverse backgrounds.
• Where appropriate, include community-based partners to ensure alignment of research goals and activities with community values.

Dr. Dieffenbach pledged that as part of the Director's Report going forward, a section on DEIA will be included so it stays on the radar and becomes part of who we are and what we do as part of the daily responsibility to enhance and support HIV and HIV-related research.

Update on COVID Studies

• ACTIV-2 is in long-term follow-up for safety and efficacy. There are no new agents.
• ACTIV-2d is awaiting FDA sign-off on a new study design.
• All the U.S. government-sponsored Phase 3 coronavirus vaccine studies are enrolled and in safety follow-up stages. FDA had recommended a 24-month safety follow-up period.
• Moderna mRNA-1273 vaccine has been licensed for 18yo+, and the FDA will convene the VRBPAC to discuss EUA in 6-17yr (6/14/22) and 6 months-<6y (6/15/22).
• The Novavax protein-based vaccine will also be reviewed at VRBPAC to seek EUA authorization and the Sanofi EUA submission is planned for mid-June.

Ending the HIV Epidemic (EHE)

• Activities related to EHE crosses all parts of HHS activity and we play a role through the CFAR Program. The goal of the EHE is to reduce new HIV infections by 75 percent in 5 years and 90 percent in 10 years. It started with several targeted high-burden counties and states with substantial burden. NIMH- and NIH-funded Centers for AIDS Research (CFARs) are well positioned to be in places of ongoing EHE activities in priority jurisdictions.
• The approach taken was summarized and involves using an interagency process to accelerate and optimize the effective implementation. This includes community engagement and partnership, collaboration with CDC and HRSA on implementation questions to get innovative strategies that are based on and that address real-world constraints and facilitate adaptations for the specific context of many of the jurisdictions.
• It is a cycle of discussion with CDC and HRSA raising issues which, when implemented, are mutually helpful to the three organizations and then also working with community to identify the questions that are of general interest to them.
• An overview of where projects were implemented was discussed. Of the 135 projects funded through the EHE to date, the vast majority of these have been implemented through community-based organizations, the health department, and much smaller amounts within the college or universities and faith-based/spiritual organizations.
• The themes of the 135 projects that have been worked on and the numbers of projects per year from FY 2019 to FY 2021 were reviewed. This included strategic partnerships, working with racial and ethnic minority populations, specifically targeting cis gender, heterosexual women, particularly related to PREP uptake and developing data-driven communication strategies, and we looked at social determinants of health of HIV using an intersectional framework. A list of the five proposed EHE priority areas for project development in FY 2022 was presented. These are currently undergoing review for a round of supplements based in the five targeted areas.
• The EHE focus areas for 2023 and beyond include expanding the status neutral approach as a way of battling stigma, mitigating HIV-related disparities, and improving the health outcomes and the health-related quality of life of people aging with HIV.
• A journal (JAIDS) supplement in Spring/Summer 2022 will include ~30 articles reporting findings from EHE projects.
• A hybrid EHE meeting is scheduled for September 15 in Birmingham, Alabama, to look at research and community collaborations towards EHE. The meeting objectives are to share best practices and lessons learned.

Public Comments Received
Public comments were received recently from the Herpes Cure Advocacy urging NIAID to re-evaluate and prioritize research on herpes simplex virus (HSV). There are plans underway between NIAID and CDC to hold a workshop in the fall of 2022 to look at the status of the research on control and prevention strategies, and identifying challenges, gaps, and opportunities for future work focused on HSV infection and disease.

Another comment complained that the Council and ARAC meetings should be open meetings. Both are open meetings and are Videocast for viewing by the public. Also, we received public comment regarding concerns about how animal research is being conducted.

Questions/Comments:

Comment: I was happy to see the HSV work getting some attention. There is a recognition within this group of the substantial attributable risk for HIV acquisition due to pre-existing genital disease with HSV.
A: We will continue to work closely with the NIAID DMID and their STI group to address these overlapping areas of interest.

Q: I was curious what the conversations have been or if there is any progress in conversations to engage historically black colleges, historically black medical schools, and other minority-serving organizations, based on the slide that you put up, about engaging diverse groups in the research and building out that capacity.
A: Within NIAID we have brought in several of the medical schools to be part of the CoVPN and those activities have continued largely through the NIAID DMID group. The Infectious Diseases Clinical Research Consortium (IDCRC) has continued to maintain those linkages to bring those groups within a larger clinical trials framework than is available for what we're currently doing in the Division of AIDS. There is sharing across the Institute and making sure that we're giving organizations opportunity that are commensurate with and can grow with their potential.

NIH Office of AIDS Research (OAR) Report:

Enhance the HIV Workforce and Promote Diversity
Maureen Goodenow, Ph.D.

This presentation discussed the role of OAR and is part of the ongoing strategy to share OAR perspectives with NIH Institutes, Centers, and Offices (ICOs) and their Councils more broadly. This focused on two key areas in which the NIH OAR influences the HIV research workforce:

1. First- the OAR listening sessions.
2. Second- the OAR initiatives that support early-career investigators, with a focus on diversity.

An overview of OAR was presented and included the following key points:

• OAR, embedded within the Office of the NIH Director, was established by Congress nearly 35 years ago by legislation that defined the activities, roles, and its responsibilities.
• OAR Director, appointed by the HHS Secretary, reports as the Associate Director for AIDS Research to the NIH Director.
• HIV research funding comprises about seven percent of the overall HIV budget and currently totals close to $3.2 billion annually.
• OAR is responsible for the allocation, tracking, and reporting of the NIH HIV funding across the ICOs, and for defining the NIH Strategic Plan for HIV and HIV-related research.
• OAR's priority activities comprise four key functions: to convene, catalyze, coordinate, and communicate HIV-related research across the NIH. For these activities, emphasis was placed on the need to ensure diversity and inclusivity and to combat racism in all its forms, and to ensure the sustained success of the NIH HIV research enterprise.
• The NIH UNITE Initiative is an agency-wide effort to identify and address structural racism within biomedical research and bolster the efforts of NIH offices involved in diversity, equity, inclusion, and accessibility.
• NIH OAR works closely with other HHS agencies to carry out the mission with input and guidance from the OAR Advisory Council (OARAC).
• OARAC provides advice to OAR on the planning, coordination, and evaluation of evolving research priorities and other HIV activities conducted or supported by the NIH.
• OARAC's role as an advisory body includes ex-officio members, some of whom represent the HHS, the NIH Office of the Director, CDC, Veterans Affairs, and the Department of Defense. Other ex-officios represent councils of NIH ICs with the largest proportion of HIV funding.
• OAR works across the NIH ICOs to advance research to EHE, improve health outcomes for people with HIV, and ensure that the research funding is directed at the highest priority areas.
• Funding distributions across NIH ICs were summarized and discussed.
• OAR continues to organize formal listening sessions to hear directly from diverse stakeholders.
• The NIH Strategic Plan for HIV and HIV-related research developed by OAR was discussed. This current plan covers fiscal years 2021 through 2025 and features four strategic goals. Strategic Goal 4 was emphasized, which is: build human resource and infrastructure capacity to enhance sustainability of HIV research discovery and the implementation of findings by a diverse and multi-disciplinary workforce.
• In the past 2 years, the NIH OAR has conducted a systematic stepwise approach effort to support HIV early-career investigators with a focus on diversity. Activities include a portfolio analysis and four listening sessions to understand the issues affecting junior HIV researchers. Some of the themes that emerged included diversity, mentoring, peer review, funding mechanisms, networks, and the impact of COVID-19.
• In response to all the input received, NIH OAR developed an early-career investigator webpage to centralize relevant information for investigators and provide easy access to grant opportunities and other resources in one place.
• In 2020 and 2021, OAR conducted a portfolio analysis of early-stage investigators. Across the NIH enterprise, there was a 50 percent increase in the number of new researchers, from 900 in 2017 to almost 1,400 in 2020, since the inception of the Next Generation Research Initiative.
• In April 2022, OAR convened its first workshop for early-career investigators in HIV/AIDS. The workshop aimed to stimulate scientific exchange, networking, and collaboration, facilitate interactions, and increase familiarity about the NIH review and funding processes.
• Moving forward, NIH OAR will continue to prioritize the support for a diverse HIV research workforce. Based on the tremendous interest in the first HIV European Congress of Immunology (ECI) workshop, plans are underway to coordinate with the NIH HIV/AIDS Executive Committee (NAEC) additional events for early-career HIV investigators and continue to update the website with timely and relevant resources.
• We will continue to monitor and support implementation of research workforce objectives of the in-house as well as the NIH UNITE initiative.
• The next OARAC meeting will be held on June 23, 2022, and will be a live NIH Videocast meeting open to the public.

Discussion:

Q: Regarding diversity: I see a real commitment from the NIH and OAR about encouraging diverse participants in research. The biomedical workforce is being depleted, meaning people are really feeling disillusioned after this pandemic and I am concerned about the pipeline for infectious disease fellows. I know everyone's working on this and we've already made such great efforts, like increasing the payline for K23s at NIAID and K08s, and increasing support for CFARs, which developed early-stage investigators. But the diversity aspect is really putting designated grant money towards people who are diverse, as much as you can, within the parameters of the law that are specifically for URM.
A: We agree and the new initiative that will be presented next represents an NIAID-wide effort to specifically address this point. The keyword that you said there was within the limits of the law. We all do the best we can and there are things that are law and then there are things that are guidelines and guidelines are meant to be not broken but bent. CFARs continue to be a massive source of innovation and have continued to be a source of training minority investigators. The biggest problem we have is that we are late in the pipeline. We are at the end and the thing about what CFARs have started to do is move into high schools and that is so critical for us for the future.

Q/Comment: The NIH Office of Data Science Strategy (ODSS) has launched a program: Enhancing Research Diversity and Participation in the AI Workforce, and I'm wondering if that type of a model might be something to consider. To the points that were made earlier about the involvement of HBCUs and reaching out to people very early in their careers, I think this initiative is targeted at doing exactly that. So that might be something to explore.
A: No doubt.

Q: Are you all using any sort of tool to look at your funding opportunities, do like an equity or diversity fitness assessment of what goes out the door?
A: We have done that and it's abysmal; hence the reason why we want to do some things that are really focused and targeted and continue to do what we can to fix the rest of it.

Comment: I just wanted to point out to people who are interested in more information, Dr. Agarwal put in the chat about the Office of Data Science Strategy (ODSS), also the Advisory Council to the [NIH] Director is meeting this week and there's going to be discussion both about the UNITE Program as well as report-out from the Office of Data Science Strategy. In addition, at the OARAC meeting later this month, the Director of NIH ODSS, Dr. Susan Gregurick, will deliver a presentation.

Concepts – Approval Requested

NIAID Division of Extramural Activities

NIAID Research Opportunities for New and “At-Risk” Investigators to Promote Workforce Diversity
LeShawndra Price, Ph.D.

The goal of the proposed R01 grant initiative is to support independent research in all NIAID mission areas to support new investigators (NI), early-stage investigators (ESI), and at-risk investigators from diverse backgrounds as defined by the NIH's interest in diversity. New investigators are defined as those who have not competed successfully for substantial NIH independent funding and ESIs (a subset of new investigators) are those who are within 10 years of their terminal research degree or end of postgraduate clinical training. At-risk investigators have had prior support as PIs on a substantial research award and less successful at securing a substantial research grant award in the current fiscal year will have no substantial research funding in the following fiscal year. Diversity at all levels—from the kinds of science to the regions in which it is conducted to the backgrounds of the people conducting it—strengthens the research enterprise and contributes to excellence in research training environments.

NIAID’s Commitment to Diversity
Aligned with the NIH, NIAID recognizes the importance of addressing scientific workforce diversity to ensure that there is a pool of highly talented scientists from diverse backgrounds capable of furthering its mission. This proposed initiative is aligned with the Next Generation Researchers Initiative enacted through the 21st Century CURES Act which is intended to promote and provide opportunities for new researchers and early research independence and enhance workforce diversity.

The initiative also is aligned with the NIH Strategic Plan for HIV and HIV-related research and the National HIV/AIDS Strategy which specifically encourages training and expansion of the diverse HIV workforce by further developing and promoting opportunities to support the next generation of HIV providers, including researchers and others from underrepresented populations.

The long history of NIH funding programs to enhance diversity was described. Recently, encouraging trends such as increased R01 applications submitted to the NIH and a modest increase in support to investigators from underrepresented groups. The NIAID piloted Enhancement Awards for Underrepresented Minority Researchers in HIV/AIDS and the Enhancement Awards for Underrepresented Minority Scientists approaches were highlighted but disparities remain. Due to legal decisions regarding the use of gender, race, or ethnicity in funding decisions, these prior efforts were discontinued. Within the last year at the NIH, several other NIH ICOs have launched similar programs to accelerate enhancing diversity at the R01 level.

Discussion:

Q: How do you determine what level of funding to allocate for such a program because clearly the need is large and could even be expanded further? Is this a pilot phase? How will this then be expanded if it's working well and if there's a big demand for this type of support?
A1: I do believe that this first phase will set the stage and we'll be able to have a better idea of how many applicants we can expect and from there we'll potentially be able to persuasively encourage additional resources to be allocated. At this first stage, we proposed an initial idea for what we thought might be a good starting point and then negotiated within our leadership, and working with our Budget Office, to come up with what we might be able to do. So, this is a pilot phase, and we'll see how things go after this and what we're able to do in the future.

A2: There has been tremendous effort at the T32 level to expand diversity, and also through the Ks. So, this really is a very important and logical step to encourage and support this effort.

Basic Sciences Program

Defining Mechanisms of HIV Induced Inflammation and Immune Activation During Suppressive ART
Gerard Lacourciere, Ph.D.

The objective of this proposed initiative is focused on defining molecular mechanisms by which HIV proteins and/or nucleic acids induce inflammation and immune activation during viral suppression. The background of this initiative was summarized, and key points included:

• Antiretroviral therapeutics make viral suppression as achievable, sustainable goal in most people living with HIV (PLWH) who adhere to that treatment.
• PLWH are living longer yet they continue to experience an elevated risk of chronic health complications, particularly cardiovascular disease, cancer, cognitive impairment, and frailty.

The role of the HIV reservoir in infected cells was briefly reviewed. This HIV reservoir is very heterogenous and some HIV infected cells remain totally silent while suppressed under ART. There can be subpopulations of cells that are capable of transcribing viral RNA or translating viral proteins or can replicate fully intact viral viruses. Understanding the reservoir at the single cell level can provide additional critical information of heterogeneity. These pro-viruses and/or their products may be strong contributors to the ongoing issue associated with HIV-induced inflammation and immune activation.

Other key points were:

• HIV pro-virus is capable of transcribing novel unspliced HIV RNA in HIV-infected individuals on HART.
• Defective pro-viruses are capable of expressing HIV proteins. These have been proposed to be biologically active and play a role in HIV pathogenesis. For example, the HIV Nef protein was shown to be associated with inflammation.

The scope of this proposed R61/R33 bi-phasic concept described a basic research phase (3 years) and an applied research phase (2 years). The scope of research for this initiative will include:

• Determining the HIV RNA and protein landscape in different cellular subpopulations harboring intact and defective provirus in the context of ART and the mechanisms and pathways by which HIV RNA and proteins expressed under ART might lead to inflammation, immune activation, and immune exhaustion (R61 Phase).
• Developing novel therapeutic strategies, intended to be used in the context of ART, to inhibit HIV expression or alter pathways resulting in HIV-induced inflammation immune activation, immune exhaustion, and validating these strategies in animal models (R33 Phase).

Nonresponsive areas of research that will not be supported were listed. This initiative fits at the intersection of basic and translational research in the DAIDS portfolio.

ARAC reviewers’ comments for this initiative and the subsequent responses were summarized.

Discussion: None

NIH Centers for AIDS Research (CFAR)/Developmental Centers for AIDS Research (D-CFAR)
Eric Refsland, Ph.D.

Two concepts for reissue were presented.

The purpose of the CFAR Program is to foster high-quality HIV research by increasing collaborations in research across disciplines at an institution or between institutions and enhance the translation of basic research findings into vaccine, therapeutic, prevention, and HIV cure concepts, maximizing efficiency and cost effectiveness. This is accomplished with a center P30 grant mechanism and these concepts are presented for approval for a reissue of the CFAR and the D-CFAR Programs.

The background of this concept was presented. Key points included:

• The CFAR Program was established in 1988 to increase collaborative science and provide infrastructure support to institutions with at least $10 million in ongoing NIH HIV-related research activities.
• Currently, there are two separate funding opportunities: CFAR and Developmental CFAR (D-CFAR). Both of these provide shared infrastructure support that is not available through other grant mechanisms and brings together multiple disciplines while giving the institution the scientific and fiscal flexibility to respond to the needs of our investigators.
• The D-CFAR Program is for institutions that have the critical mass of HIV researchers but have gaps to fill and provides five years of funding to address those gaps and strengthen a program to become competitive for a full CFAR.
• Currently, there is a four-tiered structure to these programs.

The program emphasizes interdisciplinary collaboration across all areas of HIV/AIDS research. The contribution of the 11 NIH institutes funding CFAR was discussed with NIAID the largest contributor of $27M per year. The CFAR Program is highly multidisciplinary with around one-third of the total NIH HIV/AIDS budget awarded to institutions with a CFAR or D-CFAR program. Currently, there are 19 CFAR and D-CFAR sites.

The P30 grant structure and CFAR pilot awards with resulting grants were summarized.

The CFAR investigators play significant roles in EHE and locations of the CFAR sites are well positioned to coordinate responses. The work of the EHE in the CFAR Program is focused on the implementation science and stretching partnerships beyond just coordinating the efforts between the investigators, community, implementing partners and local health departments, but also helps to synergize work and deepen collaborations.

Proposed changes to CFAR Tier funding levels and the rationale were outlined. These have not changed since 2003. An increase of $250K per year for each tier is proposed.

The CFAR’s engagement in diversity, equity, and inclusion activities on the individual CFAR level as well as program-wide efforts were described. Two examples were given:

1. The CFAR Adelante which advances HIV research in Hispanic/Latinx communities by providing mentored development to early-career investigators whose research focuses on decreasing HIV-related health disparities among Hispanic/Latinx people.
2. The CFAR Diversity, Equity, and Inclusion Pipeline Initiative (CDEIPI) which has a goal to increase the number of underrepresented minorities, black, indigenous, and people of color trainees who are engaged in HIV science at the high school, undergraduate, graduate, and postdoctoral levels to launch successful careers in science and medicine.

This is accomplished through increased collaboration with HBCUs and other minority-serving institutions, a total of more than 25 so far, and this is also coordinating our outreach to places where we haven't previously engaged.

For this reissue, a new component is proposed for the application, a one-page scorable plan for enhancing diverse perspectives (PEDP). This initially was launched by the Brain Initiative at the National Institute of Neurological Disorders and Stroke.

Other proposed CFAR core changes were summarized.

The objective of the D-CFAR program is to provide administrative and shared research support to enhance HIV/AIDS research. D-CFARs provide core facilities, expertise, resources, and services not readily obtained otherwise through more traditional funding mechanisms. The program emphasizes interdisciplinary collaboration across all areas of HIV/AIDS research. The D-CFAR program provides 5 years of funding to help build the collaborative relationships, leadership structure, core facilities and resources, and mentorship programs necessary for a standard CFAR.

Using the same structure as the CFAR program, the D-CFAR program supports research and administrative infrastructure and translational HIV/AIDS research activities at institutions that receive significant HIV/AIDS funding from NIH ICs. D-CFARs are designed to foster synergy and improve coordination of research, support emerging research opportunities, and promote efficiencies through resources shared by multiple independent laboratories. The emphasis expected in a D-CFAR application will be the identification and clear description of gaps or deficiencies that would hinder development of a competitive CFAR application, and Core facilities that would reduce or eliminate these gaps. D-CFARs are intended to promote NIH HIV/AIDS research efforts at the D-CFAR institution(s).

ARAC reviewers’ comments for these initiatives and the subsequent responses were summarized.

Discussion:

Q: Have there been any conversations at your team level about the challenges that some CFARs have had with maintaining community engagement mechanisms, recognizing that some CFARs have had significant challenges maintaining CABs and what support your team or office might be able to provide to them regarding that?
A: That has come up and we have been discussing that issue and how best to work on community engagement within the CFAR. There is the NCCC, the organization that works on the CFAR community engagement. If there are issues, that's something that we definitely need to visit. If there are CFARs that are very successful, what are they doing at their institutions to accomplish that success? It's a very important issue and we'll certainly try to figure out how best to do that.

Q: In terms of evaluation of the PEDP efforts do you have a sense of how will those goalposts be established for these programs?
A: We're fortunate in that there are other ICs starting to already do this and their applications are being reviewed and applicants are putting together their plans; no two will be exactly alike. By the time this is incorporated into the PAR and the CFAR Program, we'll have quite a bit of information on how to do that and we're in close contact with those Institutes that are rolling it out already. We have a lot to learn about that. It's a learning process for everybody involved because there's a lot of need to improve in this area. Our approach is to just lean heavily on and reach out and talk to our colleagues across different NIH ICs to come up with our plan for that.

Therapeutics Research Program

Analyzing Early Events in Tuberculosis (TB) and TB/HIV Infection to Identify Interventional Targets
Robert Mahon, Ph.D.

The objective of this new R01 grant initiative is to identify the essential immunopathogenesis mechanisms in early Mycobacterium tuberculosis (MTB) and TB/HIV infections, to identify novel targets for host-directed interventions. The importance and background of this initiative was presented. This covered: 

• People living with HIV are at increased risk of TB disease and recurrence, reinfection, and poor treatment outcomes necessitating new therapeutics and preventative strategies.
• Since TB-infected individuals are only seen well into their infection, the early events of MTB infection are not a well-focused area of host-directed therapy or study.
• The first few weeks are crucial in determining the effectiveness of the immunological response to, MTB, and the ultimate clinical outcome.
• Distinct myeloid and lymphoid cells appear to play central roles in the outcome before the development of the adaptive immune responses and how MTB is actively suppressing the key immune functions during this period for its survival.
• SIV and HIV modulate in immunity that is involved in early MTB infection within the lung by:
  • Impacting alveolar macrophage biology
  • Exacerbating MTB induced delay in T cell responses

While this has not been well or even effectively studied in the context of actual, established HIV infections and new MTB infections, there are theoretical models that suggest that these defects can lead to higher MTB burdens. This initiative seeks to stimulate this area of research, of new TB infections in established HIV cohort or animals.

One example of published MTB research to address the inability to activate T-cells involves enhancing the activity of Mycobacterium bovis BCG, currently the only approved vaccine for MTB. Administering BCG pulsed with dendritic cells containing MTB antigen led to complete control of MTB in challenged mice early after infection. Additionally, in the past few years, previously unexplored immune cells, e.g., eosinophils and innate lymphoid cells are now considered as having a role in controlling TB infection. Additional research is needed to further understand this area and this initiative may be able to support such studies. Ultimately this initiative seeks to refocus attention to the early MTB infection from where the host-directed therapeutic research has primarily been focused on that being the granuloma and inactive TB.

The scope of the initiative would be mechanistic studies of MTB or MTB/HIV or MTB alone infection before full development of adaptive immune functions, in the alveolar and pulmonary tissue setting that's focused on the interaction of myeloid and lymphoid cells within the alveolar and adjacent lung and effects on the development and timing of key T-cell functions, MTB immune renovations and destruction of immune cell functions, studies of how HIV, SIV, and SHIV modulate early MTB events, immunity events. This would primarily be studies utilizing small animal models and NHPs, the use of banked and human samples would also be allowed. This initiative will not support: focused primarily on latency or reactivation of established MTB infection; studies focused on single immune cell type(s) alone unless they are defining a specific component of immune evasion pathways or host cell function within a wider context; research that tests only effectiveness of TB interventions without studies to identify underlying mechanisms (e.g., immune signaling pathways); studies focused on transmission of MTB; studies primarily focused on model development; and clinical trials.

Reviewers were supportive of the concept and their comments for this initiative and the subsequent responses were summarized and addressed.

Discussion: None

Mycobacterium tuberculosis Quality Assessment (TBQA) Program
Daniella Livnat, B.Sc.

The objectives of this contract renewal initiative are to provide a resource to support the ability of laboratories to reliably perform studies of specified MTB tests, evaluate MTB technologies and specimen processes for using clinical investigations, disseminate technical and scientific data, and perform late-stage assay validation or assay testing of clinical samples in a CLIA, certified laboratory.

The importance of TBQA was discussed and included:

• The continued significant public health burden and global health, especially among PLWH.
• The continued need for rapid, accurate, and early diagnosis of MTB infection to facilitate screening and triage.
• TBQA is a critical infrastructure resource and a component of the DAIDS Quality Management System. The use of appropriate methodologies as well as reliable and harmonized testing among labs allows for between-study comparability of results and hence ability to ascertain study laboratory endpoints.

TBQA Contractor requirements were listed and included:

• Access to live biosafety level 3 (BSL3) clinical TB laboratory.
• Access to current TB instruments/methodologies (e.g., GeneXpert).
• Access to TB drugs (e.g., Delamanid).
• Dynamic (replenishable) repository of TB isolates (derived from HIV+ and HIV- individuals), characterized for sensitivity and resistance to anti-TB drugs by various methodologies.
• Access to non-sputum materials, including whole blood, serum, plasma, peripheral blood mononuclear cells (PBMCs), urine and saliva from MTB-infected and uninfected adult and pediatric individuals, with or without HIV infection, vaccinated and not vaccinated with BCG, and individuals with non-MTB respiratory diseases.
• Staff with TB clinical laboratory expertise.
• Efficient interactions with investigators/protocol teams to proactively assess and address laboratory-related needs.
• Collaboration with other DAIDS Laboratory QA resources (e.g., pSMILE).

The key tasks of this initiative:

1. To support the ability of labs to reliably perform study-specified MTB tests which includes external quality assurance (EQA). 
2. To evaluate methods and sample processes (in-house and/or multi-lab) with the purpose of facilitating the optimization, standardization, and validation of MTB assay methodologies for implementation in NIAID supported or collaborative studies.
3. To disseminate technical and scientific data.

A new contract option (additional work that, if needed, may require additional funds) is to perform late-stage assay validation and/or MTB Testing of Clinical Samples in a CLIA-certified laboratory.

Examples of TBQA accomplishments were summarized.

Reviewers were supportive of the concept, and their comments and the subsequent responses were summarized and addressed.

Discussion: None

Vaccine Research Program

Cellular Immunology Core Laboratory
Que Dang, Ph.D.

The objective of this contract renewal initiative is to have a cellular immunology laboratory that will provide a centralized service to conduct assays measuring cellular immune responses in support of preclinical AIDS vaccine studies. These include assays such as, but are not restricted to, ELISpot, flow cytometric (FACS), and activation immune marker (AIM) assays to assess and characterize antigen-specific immune cells and their responses in peripheral blood and in tissues.

Also, as the understanding of the role of other cellular functions in the development of protective antiviral immunity evolves and as assays for their evaluation are developed, this contract may incorporate assays for additional cellular-mediated functions that are found to be induced by vaccine candidates.

In DAIDS, the Vaccine Research Program has a coordinated set of contracts to comprehensively support the evaluation of immunogenicity and efficacy of candidate HIV/SIV vaccines in preclinical studies. The Cellular Immunology Laboratory (CIL) is one component of the Core Laboratories Program which supports NIAID’s Simian Vaccine Evaluation Units (SVEUs). The Core Laboratories Program is composed of four centralized core laboratories: humoral immunology; functional genomics; virology; and cellular immunology.

The importance of this contract initiative was discussed:

• Development of an effective HIV vaccine is a high priority for NIH.
• Preclinical studies in nonhuman primates or small animals are key to evaluate the immunogenicity, efficacy, and toxicity of vaccine candidates; to de-risk the product/platform in costly GMP manufacturing, and to inform and guide Phase 1 clinical trial studies.

Current activities and supported SVEU studies at the cellular immunology core laboratory were reviewed. The current contract has developed 28 validated assay SOPs and 20 validated equipment SOPs.

Experimental activities of the laboratory were extensively described in detail with data. Procedures are in place, both internally and externally, to ensure rigor and reproducibility of studies.

The new CIL contract may support cellular analyses performed in small animal studies. The new contract may be called upon to conduct assays in support of TB vaccine studies in the context of Mycobacterium tuberculosis/SIV-HIV co-infection. The CIL will be required to deposit all data into a prescribed database (to be determined). Lastly, the contractor will implement an independent quality assurance program.

Reviewers were enthusiastic of the concept, and their comments and subsequent responses were summarized and addressed.

Discussion:

Q: How are protocols chosen and how is everything coordinated? It seems like there's a large coordination effort that needs to be done, or that is done. Are there areas where things can be shared, such as bioinformatics that you were describing?
A: The studies are chosen on programmatic priority, and we are looking to answer specific questions. Sometimes it's a platform question. Some of the examples I gave, e.g., to see if a slow delivery of an immunogen will be superior to what is conventionally given which is a large bolus of the immunogen; the other study that we're doing currently, which was P213, is to confirm - repeat, actually, and confirm - what they observed in their study, which was that cellular immune responses were able to lower the threshold of neutralizing antibodies that were shown to be protective in their study. That’s how the studies are chosen.

RE: The bioinformatics. The answer to your question is complicated because some of these platforms are proprietary. We have industry that we sometimes support studies for, or we have investigators who are not quite yet ready to advance their product and it's exploratory. When it is possible, we certainly do intend to make available the information and that's why in part we want to have a centralized database so that when the data are able to be shared, then we can invite the field to look at the data more closely.

Q: Would this be a core resource lab for multiple grants to feed into, to use this resource to enhance their evaluation of immunity to infectious diseases?
A: The contract is currently set up to support primarily our preclinical studies conducted through the SVEU. Unfortunately, our budget at this time is not enough to support other grant investigators, but occasionally on our other core contracts, we did have some available funding where we are able to support other investigators for their grant research.

External Quality Assurance Program Oversight Laboratory (EQAPOL)
Milton Maciel Jr., PharmD, Ph.D.

EQAPOL is a contract that is up for its second renewal since its inception in 2010. EQAPOL's overarching objective is to maintain a facility to support the development, implementation, and oversight of external quality assurance programs to support DAIDS clinical trials that use HIV vaccines and monoclonal antibodies. 

EQAPOL's missions are focused on the specialized assays and proficiency programs that ensure competency and comparability among multiple laboratories, testing multiple vaccine candidates as well as cross-population comparisons. EQAPOL serves as a mechanism to provide the sponsor and regulatory agencies, for example the FDA, with confidence that individual laboratories are generating data to support new vaccine formulations and investment. These activities assure decision-makers that results are reliable and accurate and enable data comparison and prioritization of the best immunogens.

EQAPOL Contract Activities: These can be divided into quality assurance and operational activities. Among the quality assurance activities, are the proficiency tasks and programs, such as the ELISpot, flow cytometry, the Luminex for cytokines, and the HIV incidence assay. Another important program is the Viral Diversity Program which procures, establishes, and characterizes HIV virus panels. EQAPOL also holds the PBMC bank and reagent repository. Those samples are available upon request for different purposes, such as assay development. For all programs, EQAPOL maintains a web database which is accessible by the participants.

Operational activities include advisement on assay validation, regulatory and compliance, and statistical issues. Additionally, EQAPOL works on the optimization and transference of technologies between laboratories, as well as development of validation programs for novel assays. EQAPOL serves 78 unique active sites worldwide that participate in one or more of the proficiency testing programs. These include HVTN sites in Seattle and Cape Town or U.S. military (MHRP) programs in Silver Spring, Maryland, and AFRIMS in Thailand.

COVID-19 Related Activities: The SARS-CoV-2 Antibody Assay Monitoring (SAAM) program arose as part of EQAPOL in response to the urgent need to develop safe and effective vaccines and immunotherapeutics against COVID-19. The SAAM Program supports reliable transference of methodologies from the laboratories to Contract Research Organizations to assess the vaccine response which guaranteed the results could be used for submission to the FDA and to investigate correlates of protection.

The SARS-CoV-2 Neutralizing Assay Concordance Survey (SNACS) evaluates the performance and concordance of a large number of SARS-CoV-2 live virus and pseudovirus neutralization, Angiotensin-converting enzyme 2 (ACE2) Inhibition, and binding assays that are developed by academic laboratories and Contract Research Organizations.

Reviewers were supportive of the concept, and their comments and subsequent responses were summarized and addressed.

Discussion: None.

Ballot Voting Outcome:

The voting members of the Committee unanimously approved the seven concepts presented today.

VI. Adjournment

The meeting of the Council adjourned at 3:58 p.m., on Monday, June 6, 2022.

We do hereby certify that, to the best of our knowledge, the foregoing minutes are accurate and complete.
 

Council will formally consider these minutes at its next meeting; any corrections or notations will be incorporated in the minutes of that meeting.