NIAID Council Minutes January 30, 2024

The 206^th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened virtually at 10:30 a.m. on Tuesday, January 30, 2024. Dr. Jeanne Marrazzo, Director, National Institute of Allergy and Infectious Diseases (NIAID) presided as chair.

In accordance with the provisions of Public Law 92-463, the meeting was open to the public from 10:30 a.m. to 11:45 a.m. and from 1:00 p.m. to 4:13 p.m. The meeting was closed to the public from 8:30 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

Table of Contents

I. Review of Grant Applications
II. Remarks of the Director, NIAID— Jeanne Marrazzo, M.D., M.P.H.
III. Guest Speaker—Monica Bertagnolli, M.D., Director, National Institutes of Health
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 4,855 research and training applications with primary assignment to NIAID for a requested amount of $1,837,012,768 in first-year direct costs and recommended approval of 2,565 applications with $1,158,501,499 in first-year direct costs.

II. Remarks of the Director, NIAID— Jeanne Marrazzo, M.D., M.P.H.

Dr. Marrazzo opened the Council session by welcoming visitors to the meeting. She introduced two ad hoc members: Dr. Gideon Lack, Professor of Pediatric Allergy at King’s College London and Head of the Children’s Allergy Service at Guy’s and St. Thomas’ NHS Foundation Trust, and Dr. Robert Wood, Professor of Pediatrics at Johns Hopkins University School of Medicine, Professor of International Health at Johns Hopkins Bloomberg School of Public Health, and Chief of the Eudowood Division of Allergy and Immunology in the Johns Hopkins Children’s Center.

Consideration of Minutes of Previous Meeting

Council considered the minutes of the September 11, 2023 meeting and concepts that had been presented and approved them as written.

Staff and Organizational Changes

Dr. Marrazzo noted that this was her first Council meeting as NIAID Director. She then announced appointments and transitions that have taken place at NIH since the last Council meeting.

On January 10, 2024, Dr. Marrazzo was ceremonially sworn in as the new NIAID Director.

Dr. Monica Bertagnolli was sworn in as the new NIH Director on December 6, 2023. She is the 17^th NIH Director, and the first surgeon and second woman to hold this position. Dr. Larry Tabak resumes his role as NIH Principal Deputy Director after serving as Acting NIH Director from December 20, 2021, to November 8, 2023.

Dr. W. Kimryn Rathmell was appointed Director of the National Cancer Institute.

Dr. Tara Schwetz was named Director of the Division of Program Coordination, Planning, and Strategic Initiatives in NIH’s Office of the Director.

Kate Klimczak was selected as the NIH Associate Director for Legislative Policy and Analysis.

Dr. Lyric Jorgenson was appointed NIH Associate Director for Science Policy and Director of NIH’s Office of Science Policy.

Dr. Victoria Shanmugam was named inaugural Director of NIH’s Office of Autoimmune Disease Research in the Office of Research on Women’s Health.

At NIAID, Dr. Mike Mowatt retired as Director of the Technology Transfer and Intellectual Property Office. Dr. Surekha Vathyam is serving as Acting Director.

In the Division of AIDS, Brendan Cole was selected as Chief of the Workforce Operations, Communications, and Reporting Branch.

In the Division of Intramural Research, Dr. Irini Sereti is Chief of a newly established laboratory that merged the Laboratories of Immunoregulation and Molecular Microbiology.

Dr. Patrick Hanley was named Chief of the Rocky Mountain Veterinary Branch.

Judit O’Connor was selected as the new Director of NIAID’s Office of Mission Integration and Financial Management.

Tributes and Awards

Dr. Marrazzo paid tribute to Dr. Ada Adimora, who passed away on January 1, 2024. She had served as a member of NIAID’s Advisory Council and AIDS Research Advisory Committee.

Dr. Marrazzo recognized Dr. Karin Bok, Director of Pandemic Preparedness and Emergency Response at NIAID’s Vaccine Research Center (VRC), who received the HHS Secretary’s Award for Meritorious Service. Dr. Bok played a major role in the HHS Coordination Operations and Response Element that contributed to the accelerated development and testing of vaccines against SARS-CoV-2 and was also involved in setting up Project NextGen.

Dr. Marrazzo also recognized Drs. Katalin Karikó and Drew Weissman, both NIH grant recipients, who were awarded the Nobel Prize for their groundbreaking research on messenger RNA that enabled the rapid development of mRNA vaccines during the COVID-19 pandemic.

Meetings and Events

On December 14, 2023, President Biden visited the NIH Clinical Center to discuss efforts to reduce the costs of prescription drugs.

On January 18, 2024, a portrait unveiling ceremony was held at Fishers Lane recognizing the distinguished career of Dr. Anthony Fauci, who served as NIAID Director for nearly 40 years.

Dr. Marrazzo summarized several policy-related changes that have been or are in the process of being implemented.

• NIH is revising its grant review process by simplifying the peer review framework for NIH research project grants due on or after January 25, 2025.
• NIH has designated people with disabilities as a Population with Health Disparities.
• The White House Women’s Health Research Initiative was established within the Office of the First Lady to advance women’s health research in the United States.
• The NIH Advisory Committee to the Director Working Group on Re-Envisioning NIH-Supported Postdoc Training made recommendations to improve NIH-supported postdoctoral training.

NIH is looking for input on its Strategic Plans for Data Science and Autoimmune Disease Research.

NIAID is developing a new Strategic Plan; the last version was published in 2017. Dr. Marrazzo outlined the proposed priorities and additional priorities and themes (i.e., operational, capacity, and crosscutting) that will be considered.

In October 2023, two international delegations visited NIAID. A delegation of five scientists from the Cuban Academy of Sciences toured the VRC and discussed priorities around emerging and re-emerging infectious diseases, dengue virus, and the importance of scientific exchange. A delegation from the Serum Institute of India met with Institute leadership and staff from across NIAID to discuss ongoing and new areas for collaboration on therapeutic and vaccine manufacturing.

Budget Update

The President is required to submit his annual budget to Congress by the first Monday in February. The fiscal year (FY) 2025 budget will be released after the President’s State of the Union address.

At the current time, NIAID is operating under a continuing resolution (CR) that expires on March 8, 2024. Congress continues to work toward an agreement on the FY 2024 annual appropriation.

Dr. Marrazzo compared NIAID’s FY 2023 enacted budget to the proposed FY 2024 budget. Under the current CR, NIAID is funded at the FY 2023 enacted level, which is $6,562 billion.

Dr. Marrazzo presented NIAID’s FY 2024 interim financial management plan. Our R01 payline is set at the 8 percentile for established principal investigators (PIs) and the 12 percentile for new PIs. NIAID will fund noncompeting and competing grants at 90 percent of the approved and committed funding levels. Competing research initiatives will be cut up to 30 percent from their planned budget level.

Congressional earmarks for FY 2024 are estimates but expected to be similar to FY 2023 enacted earmarks except for tickborne disease research, which is no longer earmarked. However, for tickborne disease research the Institute plans to maintain a level similar to FY 2023 funding.

Legislative Update

Dr. Marrazzo noted that Mike Johnson was named 56^th Speaker of the House of Representatives.

On October 17, 2023, the Majority Clerk of the Senate L-HHS Appropriations Subcommittee visited NIH, and toured buildings and facilities and discussed research updates.

On November 9, 2023, bipartisan bicameral L-HHS staff visited the VRC. They met with NIAID Director Dr. Marrazzo and VRC Director Dr. Ted Pierson to discuss the science behind developing the RSV monoclonal antibody for the treatment and prevention of RSV in infants.

Dr. Marrazzo acknowledged NIAID staff who have participated in many Congressional briefings and events on behalf of NIAID.

Other Information Items

Dr. Marrazzo began by giving an update on COVID-19. She presented data on the number of recent hospitalizations and recent SARS-CoV-2 viral activity in wastewater and noted that a recent spike in SARS-CoV-2 viral activity in wastewater has not been matched by similar spikes in COVID-19 hospitalizations or deaths. NIH COVID-19 Treatment Guidelines were developed to provide clinicians with guidance on COVID-19 patient care in a rapidly evolving field. They’ve been updated 72 times and the last update is anticipated to be in February 2024. Dr. Marrazzo also mentioned that Long COVID and its pathology remain a research focus for the Institute.

On December 1, 2023, Dr. Marrazzo participated in a fireside chat with Dr. Bill Kapogiannis, Acting Associate Director for AIDS Research and Acting Director of NIH’s Office of AIDS Research, to commemorate World AIDS Day. Dr. Marrazzo summarized recent research findings from several HIV/AIDS studies.

Dr. Marrazzo then provided an update on NIAID-funded research related to sexually transmitted infections (STIs). The Institute sponsored three clinical studies to evaluate the safety, pharmacokinetics, and antimicrobial activity of zoliflodacin. The Global Antibiotic Research and Development Partnership conducted a Phase III noninferiority trial of zoliflodacin for gonorrhea that showed the oral antibiotic inhibits replication of bacterial DNA and is safe and as effective as standard therapy for uncomplicated gonorrhea.

Dr. Marrazzo summarized NIAID research activities to address the surge in newborn syphilis cases, including a funding opportunity soliciting research to develop new and improved diagnostics, a longitudinal study to obtain high-quality syphilis specimens for diagnostic research, and small business contract proposals to identify alternatives to benzathine penicillin G for treatment. She also presented results from two studies of doxycycline post-exposure prophylaxis for STIs that had different outcomes in different populations.

She concluded with brief updates on other topics of interest, including a new international trial comparing clinical outcomes in patients with gram-negative bacteremia following blood culture evaluation either by rapid antibiotic susceptibility testing or standard methods; a Supplement published in The Journal of Infectious Diseases that summarized proceedings from a workshop on pandemic preparedness that NIAID hosted in November 2021; the release of NIH’s Strategic Plan for Herpes Simplex Virus Research and a planned notice of special interest (NOSI) on Research to Stimulate Diagnostics, Therapeutics, and Vaccine Development for Herpes Simplex Virus; and promising results from the OUtMATCH trial that showed that omalizumab treatment significantly increased the amounts of multiple common foods that food-allergic children and adolescents could consume without an allergic reaction.

III. Guest Speaker—Monica Bertagnolli, M.D., Director, National Institutes of Health

Dr. Bertagnolli introduced herself to NIAID’s Advisory Council members and described how her background and experiences informed her career choice.

She then presented several areas that will be priorities for her as NIH Director. The first is supporting early-career scientists and working to accelerate strategies and programs that would give them more support. Dr. Bertagnolli summarized the recommendations of the NIH Advisory Committee to the Director Working Group on Re-Envisioning NIH-Supported Postdoctoral Training, which include increasing pay and benefits for NIH-supported postdocs, facilitating the transition of postdocs to the next career stage, promoting training and professional development for postdocs and their mentors, and supporting safe and diverse perspectives and research environments.

The next topic Dr. Bertagnolli addressed was NIH’s budget. She noted that NIH hopes to avoid drastic budget cuts but asserted that a flat budget would also have a significant impact as we continue to try to fund the best science and develop the next generation of researchers.

Dr. Bertagnolli then discussed the declining health of the U.S. population, noting that U.S. life expectancy has been decreasing, which was a trend that was occurring before the COVID-19 pandemic, while health expenditures have been increasing. The decline in life expectancy appears to be related to an increase in mortality among working-age adults (ages 25 to 64) with deaths related to drug and alcohol use, suicide, and cardiometabolic diseases.

Dr. Bertagnolli shared her vision and guiding principles as she works with NIH institute and center directors to develop and plan strategies. She emphasized that it’s critical to remember that NIH’s work is not finished when we deliver scientific discoveries. Our work is finished when all people are living long and healthy lives, and we need to ensure that our advances reach the people that need them and results benefit everyone.

She concluded by summarizing her priorities for NIH with a focus on connecting research to primary care to optimize outcomes for patients and expanding biomedical research data use to inform new research and improve health outcomes.

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

Dr. Rotrosen welcomed the subcommittee members to the 206^th meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting.

Dr. Rotrosen presented the following scientific and Division activities:

Staff and Organizational Changes

Nancy Bridges, M.D., Dr. Bridges retired from Federal service as Branch Chief of the Transplantation Branch in December 2023. She joined DAIT/NIAID in 2002 as Chief, Clinical Transplantation Section of the Transplantation Branch. In 2006, Dr. Bridges was promoted to Chief, Transplantation Branch. During her tenure at NIAID, she was responsible for programmatic management and scientific and budgetary oversight of a portfolio of basic and clinical research programs that included leadership of transplantation research within the Immune Tolerance Network (ITN) and the Clinical Trials of Organ Transplantation (CTOT). She represented NIH at various DHHS activities related to clinical transplantation and drove the advancement of research in organ and cellular transplantation.

Peter Gergen, M.D., Dr. Gergen retired as a Medical Officer in the Allergy, Asthma, and Airway Biology Branch (AAABB) in September 2023. Dr. Gergen joined DAIT/NIAID in 1991, moved to AHRQ in 1996, and returned to DAIT in 2003. In his time with NIAID, he led the National Childhood Inner-City Asthma Study (NCICAS), the Inner-City Asthma Consortium, and the Childhood Asthma in Urban Settings (CAUSE), becoming the central NIAID figure in our research efforts to address childhood asthma in low income, urban populations. He led numerous clinical trials supported by NIAID and was a major contributor to the National Health and Nutrition Examination Survey (NHANES) work on asthma and allergic diseases.

Lisa Wheatley M.D., M.P.H., Dr. Wheatley retired as Section Chief of the Food Allergy, Atopic Dermatitis, and Allergic Mechanisms (FAADAM) section of AAABB at the end of 2023. Dr. Wheatley joined DAIT/NIAID in 2012 as a Medical Officer and served as Section Chief of the Asthma and Airway Biology section between 2016 and 2019. In her capacity as Chief of both AAABB sections, she oversaw multiple NIAID-sponsored consortia and led several pivotal clinical studies and trials.

Wendy Davidson, Ph.D., Dr. Davidson retired as a Program Officer in the AAABB at the end of 2023. Dr. Davidson joined AAABB in June of 2011 having previously served as a Scientific Review Officer with NIAID’s Division of Extramural Activities for 3 years. For many years, Dr. Davidson led several grant portfolios including that for food allergy. She also served as a Project Scientist in many NIAID-sponsored clinical trials and observational studies and is credited for introducing vigorous research methodologies in the Atopic Dermatitis Research Network (ADRN) and the Consortium for Food Allergy Research (CoFAR).

Joy Laurienzo Panza, R.N., B.S.N., Ms. Laurienzo Panza retired as a Nurse Consultant/Project Manager in the AAABB at the end of 2023. She joined DAIT/NIAID in August 2002. In her time with DAIT, she served as Project Manager on numerous important clinical trials in the AADCRC, ADRN and ITN networks. Prior to joining DAIT, she spent 14 years as a research nurse in intramural research at NHLBI for a combined 35 years at NIH.

Patricia Fulkerson, M.D., Ph.D., Dr. Fulkerson has been selected as the new Section Chief for FAADAM, AAABB, NIAID. She first joined the FAADAM section as a Medical Officer in August 2019. She completed the Medical Scientist Training Program at the University of Cincinnati College of Medicine in 2007 and continued her clinical training with a residency in Pediatrics and fellowship in Allergy and Immunology at Cincinnati Children’s Hospital Medical Center. She joined the faculty at Cincinnati Children’s in 2012, where her NIH-funded research and her clinical practice focused on eosinophil biology and on patients with eosinophil-associated disorders.

Amaziah Coleman, M.D., Dr. Coleman joined AAABB as a Medical Officer/Physician federal employee in January 2024. She had previously worked at AAABB in the same capacity under contract since 2021. Dr. Coleman received her M.D. degree in 2010 from the University of Mississippi Medical Center and completed her pediatric residency at the University of Arkansas/Arkansas Children followed by a postdoctoral fellowship in allergy and immunology at the University of Wisconsin School of Medicine and Public Health. In 2016, she was appointed Assistant Professor in Pediatrics at the George Washington University School of Medicine and Health Sciences and Attending Physician at Children’s National Hospital, in Washington, DC. Dr. Coleman has published original research in pediatric asthma and food allergy. Many of her publications and presentations at national meetings are focused on diversity research related to these conditions.

Tatyana Vaysman, M.D., Dr. Vaysman joined AAABB, DAIT, NIAID as a Clinical Trials Specialist/Project Manager in November 2023, after spending almost 3 years in the branch in a contract position. She received her M.D. degree from the University of Crimea and has several years of clinical research experience as a Clinical Research Coordinator and Clinical Research Associate in the public sector. She currently has primary responsibility for the studies conducted by CEGIR and is also the Project Manager for both academic and pharmaceutical industry investigator-initiated clinical trials.

Jaclyn Evans, B.S., Ms. Jaclyn Evans joined the Transplantation Branch, DAIT, NIAID as a Health Scientist Administrator federal employee in November 2023. Previously she had ably served as a Health Specialist and, most recently, as a Clinical Protocol Coordinator in the Clinical Research Operations Program, DAIT. Prior to her arrival at NIAID in 2017, she worked as a Clinical Research Coordinator at Johns Hopkins University School of Medicine.

Michael Rudokas, Ph.D., Dr. Rudokas joined the Radiation and Nuclear Countermeasures Program as an AAAS Science and Technology Policy Fellow in August 2023. He will serve as the program’s Industry Liaison. Prior to joining DAIT, Dr. Rudokas received his Ph.D. in Cellular and Molecular Pharmacology and Physiology from the University of Nevada, Reno in 2021. He then completed postdoctoral training in the Cardiovascular Research Center at the Yale School of Medicine.

Selected Funding Opportunities

NIAID

RFA-AI-23-024: Sex Differences in Radiation Research: Models, Underlying Pathways, Biomarkers of Injury, and Medical Countermeasure Responses (U01, Clinical Trial Not Allowed). The purpose of this notice of funding opportunity (NOFO) is to enable early-stage research to better understand the underlying causes of radiation-associated sex differences to advance radiation preclinical animal models, improve Medical Countermeasures (MCM) development, increase the safety and efficacy of MCMs, and advance biomarker science to assess radiation injuries.

RFA-AI-23-059: Development of Candidate Radiation/Nuclear Medical Countermeasures (MCMs) (U01, Clinical Trial Not Allowed). The purpose of this NOFO is to support investigator-initiated research that is specifically focused on all stages of development of medical countermeasures (MCMs) to mitigate/treat injuries arising from radiation exposure during a public health emergency. This funding opportunity will support the development of novel approaches within the radiation research area that may be considered for future licensure by the FDA.

NOT-AI-23-064: Notice of Special Interest (NOSI): Development of Organotypic Culture Models for Transplantation Immunology Research. The purpose of this NOSI is to support applications that focus on the development and validation of tissue-, stem-, or progenitor-cell-derived “3D” organotypic culture models (OCMs) for transplantation immunology research. As compared to traditional “2D” culture systems, OCMs offer improved modeling of tissue architecture, cell-cell interactions, and other aspects influencing tissue and organ system microenvironments. Such models could be used to investigate innate and/or adaptive immune responses to an allograft or xenograft and evaluate risk of zoonoses in the context of immunosuppression and xenotransplantation. Once validated, these models could assist in screening novel drug targets; complement or reduce reliance on in vivo transplant models; and refine personalized medicine approaches to reduce immunosuppression and/or extend allograft survival.

Division Activities

Radiation and Nuclear Countermeasures Program

Radiation and the Microbiome U01 Consortium Kickoff Meeting. On May 1, 2023, an in-person meeting was held at Fishers Lane in Rockville, Maryland, for awardees of RFA-AI-21-068, titled Development of Microbiome-Related Approaches for Diagnosis/Mitigation/Treatment of Radiation Injuries. The projects in the consortium focus on understanding the mechanisms of radiation-induced microbiome dysbiosis, and the PIs also are developing novel therapeutics to mitigate gastrointestinal - acute radiation syndrome (GI-ARS). Funding in this area of research will address an unmet need, as there are currently no FDA-approved therapeutics for GI-ARS.

Northwestern University P01 Program Meeting. On July 28, 2023, the RNCP supported “Multi-Scale Evaluation and Mitigation of Toxicities Following Internal Radionuclide Contamination” Program Project grant (P01) team were hosted at Fishers Lane for a hybrid virtual and in person programmatic meeting. The PI, Project Leads, and Core Leads each provided overviews of their accomplishments and participated in a brief Q&A and discussion session. This meeting served to bring the team members together from across the country and enhance their regular communication schedule with in-person interactions with one another as well as NIAID program staff and staff from other invited government agencies.

Advanced Technologies in Radiation Research (ATRR) Conference. On August 17 and 18, 2023, a hybrid workshop was held at the NIAID Fishers Lane Conference Center. Over 300 participants registered for the meeting with 100 in-person attendees and 20 speakers presenting advanced techniques using microphysiological systems, novel imaging techniques, computational methods for mathematical modeling and artificial intelligence, and various translational methods. The workshop was organized by an inter-agency collaboration led by NIAID, with input from NCI, NASA, and the Radiation Injury Treatment Network. The workshop was the first of its kind for NIAID, with part of the meeting held in the NIAID/BCBB Biovisualization Lab. Participants took part in an interactive presentation of data from the RNCP portfolio and donned 3D headsets to experience the virtual environment. Online attendees of the meeting also took part by observing the interactions in real-time through Zoom.

Countermeasures, Emergency Preparedness, and Responses Symposium at the International Congress for Radiation Research (ICRR). On August 28, 2023, the RNCP sponsored and chaired a symposium at the ICRR in Montreal, Canada, that consisted of two talks that examined medical countermeasures currently being developed for use after radiation exposure. In addition, two biodosimetry talks showcased biomarkers and point-of-care device research that can potentially help with triage and medical management after a mass casualty incident. Together this research helps increase the preparedness and safety of the public, which was addressed by a final talk from the Centers for Disease Control and Prevention, with information needed to respond to both domestic and global emergency medical preparedness for nuclear or radiological threats.

Development of Countermeasures from Bench to Clinic Sunrise Symposium at the International Congress for Radiation Research (ICRR). On August 29, 2023, the RNCP supported a sunrise symposium at the ICRR in Montreal, Canada, that guided researchers through the steps necessary for navigating the critical path from early discovery to eventual drug licensure. The Session’s speaker, Dr. Deborah Bunin (SRI, RNCP contractor), provided specific examples, case studies, and lessons learned to inform drug developers. The presentation also included a review of the FDA Animal Rule Guidance and the draft 2023 FDA Guidance for Industry on “Acute Radiation Syndrome: Developing Drugs for Prevention and Treatment.”

Allergy, Asthma, and Airway Biology Branch

Alpha Gal Syndrome Investigator Meeting. On September 22, 2023, a virtual meeting was held, organized by AAABB for investigators funded to study Alpha Gal Syndrome. Representatives from five research groups provided updates on funded research and discussed potential for collaboration to further research in the field.

The Role of IgG4 in Allergic Disease. On October 4, 2023, AAABB held a virtual workshop in Rockville, Maryland. The objective of this workshop was for NIAID to obtain expert input in identifying knowledge gaps in the role of IgG4 and best approaches to determine IgG4 function in allergic disease. The workshop brought together investigators in allergic disease, as well as those studying the role of IgG4 in other diseases.

2023 Annual Asthma and Allergic Disease Cooperative Research Center Face to Face Meeting (AADCRC). On October 16 and 17, 2023, NIAID sponsored the 18^th annual meeting of the AADCRC investigators in Rockville, Maryland. The 2-day virtual meeting of PIs, co-investigators, students, and program staff included presentations from 12 NIAID-funded research AADCRC Centers, as well as 4 NIAID-funded Program Project grant teams, a special session featuring the work of AADCRC opportunity fund-supported collaborative and young investigators, and a poster session featuring young investigators and trainees.

Understanding and Addressing Disparities in Asthma and Allergic Diseases Research. On December 4 and 5, 2023, AAABB held a workshop in Rockville, Maryland. The major objective of the virtual workshop was to convene experts with knowledge and experience on engaging diverse populations in asthma and allergic diseases research, and to strategize how to optimize research recruitment to better understand and address health disparities in these therapeutic areas. The workshop assembled researchers, patients, advocacy groups and diverse stakeholders to discuss these complex and important issues. The meeting ended with a panel discussion to help identify actionable items that can refine NIAID research priorities moving forward.

Basic Immunology Branch

Advancing Vaccine Adjuvant Research for Tuberculosis (AVAR-T) Annual Meeting. On September 12, 2023, the first annual meeting (virtual) of the AVAR-T contract was held. The goal of the AVAR-T program is to advance the development of preventive tuberculosis vaccines by conducting side-by-side comparison of different adjuvants in combination with Mycobacterium tuberculosis (Mtb) immunogens using preclinical models to establish adjuvant immunological profiles. The studies are expected to help identify promising vaccines against tuberculosis for clinical development and potential correlates of protection.

Unraveling Links between Chronic Inflammation and Long COVID: Current State, Challenges, and Opportunities Workshop. From September 19 to 21, 2023, this workshop was held on a virtual platform, and was jointly organized by NIAID, the National Cancer Institute (NCI), the National Institute of Dental and Craniofacial Research (NIDCR), the Office of Dietary Supplements, the National Center for Advancing Translational Sciences (NCATS), the National Eye Institute (NEI), the National Institute of Aging (NIA), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of General Medical Sciences (NIGMS). Investigators described latest advances in understanding the heterogeneous and lingering symptoms and disease manifestations, prolonged multiorgan inflammation and injuries, difficult diagnosis, risk factors, and the underlying mechanisms of the pathogenesis of Long COVID and its long-term impact on life quality. The meeting served as a forum to bring together investigators from diverse disciplines to discuss their research progress and provide opportunities for collaboration to advance the field.

Molecular Mechanisms of Combination Adjuvants (MMCA) Annual Meeting. On October 23 and 24, 2023, the annual meeting of the Molecular Mechanisms of Combination Adjuvants program took place in Rockville, Maryland. During the meeting, the participating investigators presented updates on research performed during the first 2 years of their 5-year U01 grants. Presenters spoke about novel findings relating to mechanisms of adjuvanticity in vaccines containing multiple adjuvants. The meeting featured a robust discussion of a wide range of combination adjuvants, including elucidation of novel pathways involved in adjuvantation, cutting-edge analysis techniques, and unique vaccine delivery platforms. Investigators offered feedback to one another for overcoming scientific roadblocks and discussed opportunities for collaboration and reagent sharing.

Immune Mechanisms of Protection Against Mycobacterium tuberculosis Center (IMPAc-TB) Annual Meeting. From November 15 to 17, 2023, the fourth annual meeting (hybrid) of the IMPAc-TB contracts was held. The overarching goal of the IMPAc-TB program is to identify and characterize immune responses required to protect a host from initial Mycobacterium tuberculosis (Mtb) infection, establishment of latent infection or progression to active tuberculosis (TB) disease. IMPAc-TB is the first NIAID trans-divisional program supporting studies to better understand TB immunology. The contractors are using murine, nonhuman primates and human models, functional assays and comprehensive immunologic approaches to help the broader TB vaccine community translate findings into improved vaccine strategies. Each center presented an overview of their programs, the accomplishments achieved, challenges encountered during the past year, approaches to leverage the knowledge gain by the IMPAc-TB program and provided updates about the continued collaborations between the IMPAc-TB centers.

RECOVER Pathobiology NOSI Investigator Year Two Meeting. On November 30, 2023, DAIT program staff moderated a session entitled "Immunological Consequences of PASC and Connection to other Viral Syndromes" as part of the annual web-based RECOVER Pathobiology NOSI Investigator Year Two Meeting organized by NIH leadership of the RECOVER (Researching COVID to Enhance Recovery) program. The session featured awardees from the administrative supplements for Research on Pathobiological Mechanisms of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) (NOT-OD-22-038). The researchers described their advances on topics including: predisposing factors for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and COVID long haulers; features and functions of autoantibodies against ACE2 and immune molecules developed after SARS-CoV2 infection; epigenetic alterations and phenotypes in innate immune cells and their progenitors in PASC; and the role of the superantigen- and neurotoxin-like motifs in SARS-CoV-2 spike in PASC.

Cooperative Center for Human Immunology (CCHI) Program. On December 7 and 8, 2023, the annual CCHI program meeting was held in person and virtually in Bethesda, Maryland. The program aims to support mechanistic and hypothesis-testing studies to understand human immune responses to infection, vaccination, and adjuvants, as well as immune-mediated diseases. Investigators from all eight centers presented the research progress, including recent updates on the COVID-19 studies supported by the supplement awards. Nine awardees who received the CCHI Infrastructure and Opportunity Fund in 2023 also presented their work. A virtual poster session was held for the week, allowing trainees to showcase their research. Among them, four of the posters were selected for short talks. The CCHI program continues to provide a platform for building collaborations, sharing the best practices, and leveraging resources among the groups.

Advancing ME/CFS Research: Identifying Targets for Intervention and Learning from Long COVID. On December 12 and 13, 2023, a hybrid meeting was held in Bethesda, Maryland. The goal of this meeting was to present the state of the science of ME/CFS research and identify targets for potential interventions that have arisen from the literature and clinical evidence from ME/CFS and Long COVID observations. The audience members were scientists, clinicians, patients and other ME/CFS stakeholders, and included in-person and remote participants (the latter via webcast). There were 23 speakers over the 2-day meeting, including four lived experience individuals who provided important perspective of what it is like to live with ME/CFS every day. Many speakers highlighted good research progress and clinical trials underway since the 2019 NIH meeting. The summary talk by Dr. Tony Komaroff highlighted the fact that more detailed pathways have been identified, particularly about metabolism, inflammation, and real-time imaging of cellular changes with ME/CFS. Speakers noted that several funded clinical trials are underway in ME/CFS and Long COVID, but there was a notable call for additional trials that was balanced with the need to understand the biology of ME/CFS in addition to moving towards trials and improved diagnostics and biomarkers.

Dirty mice: Leveraging Microbial Exposure for Improving Mouse Models of Human Immunity and Disease Workshop. On January 24 and 25, 2024, NIAID held this workshop as a web-based open meeting. Co-organized by DAIT and DMID, the workshop allowed researchers to discuss recent advances in developing “dirty” mouse facilities and using microbial experienced (dirty) mice to understand the influence of microbial exposure on 1) host immune responses and 2) disease progression, and to test vaccine candidates and therapeutics. The objective of the workshop was to obtain expert input for better assessing the utility of dirty mice in modeling human immunity and diseases, discussing limitations and challenges, as well as identifying solutions and future directions to promote the model. The workshop brought together NIH intramural researchers, extramural investigators, and representatives from mouse model vendors, to share information and provide opportunities for collaboration.

Transplantation Branch

Nonhuman Primate Transplantation Tolerance Cooperative Study Group (NHPCSG). On September 13 and 14, 2023, the kick-off Steering Committee meeting of the NHPCSG was held at Fishers Lane, Rockville, Maryland, and included both in-person and virtual attendees. Projects supported by this multi-institute program evaluate novel and refine existing preclinical regimens to promote the induction and maintenance of transplant tolerance in nonhuman primate (NHP) models. All projects include mechanistic studies to elucidate the immunologic basis of tolerance and/or rejection. The renewed consortium consists of one U01 and three U19 awards. The meeting included project descriptions and research updates from new consortium members, past awardees in no-cost-extension status, and Opportunities Pool project awardees. Additional presentations from partner programs, the NHP Reagent Resource and the NHP MHC and KIR Allele Discovery and Typing Technology Development contract, reviewed ongoing and developing collaborative projects. The meeting facilitated enhanced interaction among consortium members and discussion of common challenges and opportunities unique to these highly translational models.

Emerging Science and Technologies in Transplantation (ESTT). On October 11, 2023, the annual steering committee meeting for the ESTT was held virtually via zoom. The ESTT cooperative group was initiated in 2016 to stimulate new interdisciplinary collaborations and support innovation in transplantation through the application of scientific developments and technologies that have not been widely applied in transplant immunology research. The current program aims to provide novel insights into the nature of alloimmune responses and reveal new avenues to diagnose, treat and prevent allograft rejection or promote immunologic tolerance through focused research in the following three priority areas: 1) microbiota, 2) intravital imaging, and 3) targeted therapeutic delivery. The current consortium consists of five U01 awards; one focused on intravital imaging, three on targeted therapeutic delivery, and one on microbiome. The consortium members shared their progress and discussed potential collaborative opportunities. The meeting was attended by the consortium members and extramural NIAID staff.

Immunobiology of Xenotransplantation Cooperative Research Program (IXCRP). On October 25, 2023, the annual IXCRP Steering Committee Meeting was held in San Diego, California, in conjunction with “the International Xenotransplantation Association (IXA)” biannual conference and included in-person and virtual attendees. The long-term goal of the program is to expand availability of donor organs and cells by enabling use of pig organs/cells as a bridge or definitive solution to treat end-stage organ failure. The current program includes one U19 and five U01 awards focused on preclinical pig-to-nonhuman primate (NHP) models of pancreatic islet, kidney, heart, and liver xenotransplantation. IXCRP investigators presented their research progress for this 3^rd year of the funding cycle. Collaborators from the National Swine Research and Resource Center and the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center presented on the availability of genetically modified swine and specific-pathogen free baboons, respectively. The meeting attendees discussed collaborations, reagent sharing, and resource availability. Investigators have extended the survival and function of orthotopically transplanted pig kidneys for up to 4 years and hearts up to 6 months in NHP recipients. IXCRP achievements have informed recent preclinical studies of pig heart and kidney xenotransplants in decedent human models and two clinical xeno-heart transplants performed at the University of Maryland Medical Center under FDA-approved companionate use criteria.

Autoimmunity and Mucosal Immunology Branch

Primary Immune Deficiency Treatment Consortium (PIDTC), Steering Committee. On November 2 and 3, 2023, the PIDTC Steering Committee convened in a face-to-face meeting in Bethesda, Maryland. Participants discussed progress and administration of their natural history studies of treatment outcomes after hematopoietic stem cell transplantation or gene therapy for inborn errors of immunity (IEI) that include severe combined immunodeficiency (SCID) (NCT01186913 and NCT01346150), chronic granulomatous disease (CGD) (NCT02082353), Wiskott-Aldrich syndrome (NCT02064933) and primary immune regulatory disorders (PIRD). PIDTC is now in its 15^th and final year of continuous funding permitted as a member of the Rare Diseases Clinical Research Network (RDCRN). The U54 award under RFA-TR-020 is sponsored by NIAID and co-funded by NCATS. An FY 2024 application to continue operations has been submitted to NIAID.

FY 2025 Research Concept Clearances Presented to Division Advisory Council

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

Human Leukocyte Antigen (HLA) and Killer-cell Immunoglobulin-like Receptor (KIR) Region Genomics in Immune-Mediated Diseases (U01, Clinical Trial Not Allowed) This initiative will support retrospective or prospective studies to investigate the relationship between genetic variation in HLA and KIR genomic regions and immune-mediated diseases, including an individual’s susceptibility to or protection from disease onset, progression, and/or severity, and across broad racial and ethnic categories with emphasis on clinical translation of the findings.

Immunobiology of Xenotransplantation Cooperative Research Program (U01, U19, Clinical Trial Not Allowed) This initiative will support new or competing renewal U01 or U19 applications that address the key immunologic and physiologic issues required to achieve safe and efficacious xenotransplantation using preclinical pig to nonhuman primate (NHP) models or human decedent models of pancreatic islet, kidney, heart, lung, or liver xenotransplantation.

Novel Approaches for Radiation Biodosimetry and Medical Countermeasures Development (R21, Clinical Trial Not Allowed) This initiative serves as the RNCP’s only mechanism to solicit investigator-initiated, very early-stage research that will foster novel ideas (models, markers, MCMs) and aid in the development of new ideas and technologies within the radiation research area.

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

Director’s Report

Dr. Emily Erbelding, Director of the Division of Microbiology and Infectious Diseases (DMID), chaired the NIAID Microbiology and Infectious Diseases Council Subcommittee meeting on January 30, 2024. She thanked Drs. Harry Greenberg and Ken Stuart for their service, noting that this was their last Council meeting. She provided a DMID personnel update, recognizing new staff appointments made in the Division since the last Council meeting: Kaniz Khan, Office of Clinical Research Activities; Nina Kunwar, Virology Branch; and Rich Robinson, Respiratory Diseases Branch.

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

• Systemic Approaches for ESKAPE Bacteria Antigen Discovery. In November, NIAID hosted a workshop on “Systemic Approaches for ESKAPE Bacteria Antigen Discovery.” Workshop goals included identifying and discussing vaccine development challenges for resistant ESKAPE pathogens.
• Swab your Nose Inside to Find inFection (SNIFF) Study. The SNIFF study found that a protein-based COVID-19 vaccine prevented infection in adolescents during the Delta wave of the pandemic from June to December 2021. Adolescents (ages 12 through 17 years) in the United States participating in a phase 3 randomized, placebo-controlled, observer-blinded trial of the Novavax NVX-CoV2373 protein subunit vaccine were invited to participate in an ancillary study to collect nasal swabs at home twice weekly for SARS-CoV-2 testing. The study found that the vaccine was highly efficacious against SARS-CoV-2 infection, regardless of symptomatology, indicating the potential to reduce the reservoir of infections that contribute to community transmission (results were posted on The Lancet preprint server on December 22, 2023).
• Takeda’s tetravalent live, attenuated dengue vaccine, QDENGA, recommended by WHO in areas with high dengue disease burden and high transmission in children ages 6-16 years of age. DMID provided extensive support to advance the preclinical and clinical development of the vaccine, including IND-enabling toxicology studies and first-in-human clinical testing.
• Meningococcal pentavalent vaccine for Infants in Africa. Interim results from a DMID Infectious Disease Clinical Research Consortium supported study comparing the meningococcal serogroup A, C, Y, W, X conjugate vaccine with another conjugate vaccine were recently presented to WHO’s Strategic Advisory Group of Experts on Immunization (SAGE). Results showed that the pentavalent vaccine was safe and highly immunogenic at 4 weeks after the vaccine was given. Based upon these results, the SAGE recommended that all countries in the African meningitis belt introduce this pentavalent vaccine to individuals aged 9 to 18 months.

Finally, Dr. Erbelding presented three topics for inclusion in the 2025 Small Business Innovation Research (SBIR) Contract Solicitation for the Subcommittee’s consideration. All were approved by the Subcommittee:

1. Diagnostics to Detect Host Immunity to Coccidioidomycosis (Valley fever) or Histoplasmosis
2. Development of Medical Interventions for Treating Non-Tuberculosis Mycobacterial (NTM) Infections
3. Development of Rapid Diagnostics for Mycoplasma genitalium (Mg) Infection

In addition, Dr. Reed Shabman, Deputy Director of the Office of Data Science and Emerging Technologies, presented two proposed SBIR contract topics, which were also approved by the Subcommittee:

1. Software or Web Services to Automate Metadata Enrichment and Standardization for Data on Infectious and Immune-Mediated Diseases
2. Software or Web Services to Assess Quality and Reproducibility of Data and Information about Therapeutics and Vaccines

Program Update: Priorities in Tuberculosis Research. Dr. Michael Ison, Chief of the Respiratory Diseases Branch, provided an overview of ongoing DMID activities to support the development of vaccines, therapeutics, and diagnostics for tuberculosis (TB). Dr. Ison noted that TB is an incredibly complex disease and exacts a significant toll in terms of global mortality from infectious diseases.

In 2018, NIAID published its strategic plan for TB research, which identifies priorities for research that are being addressed by all components of the Institute. The Plan is currently being updated and will be available in early 2024. Dr. Ison reported that DMID is helping to address multiple priorities outlined in the Plan, including efforts to expand fundamental knowledge of tuberculosis, develop better animal models, and understand critical drivers of transmission. Additionally, DMID supports efforts to develop more rapid and accurate point-of-care testing. Furthermore, DMID-supported investigators are looking at new TB biomarkers and biosignatures and using all of these to accelerate the development of TB vaccines. He noted that DMID has also invested significantly in advanced strategies to treat and prevent tuberculosis beyond vaccines, including novel therapeutics and combinations, with the goal of developing shorter and safer treatments for tuberculosis. Lastly, he reported that DMID also has stood up a program to help cultivate the next generation of TB researchers.

Dr. Ison presented a schematic of the targeted funding programs DMID supports to address these and other TB research priorities and described several of these programs in detail, noting promising advances associated with each effort. He reported that several of these activities are being managed in collaboration with the Division of AIDS and/or the Division of Allergy, Immunology, and Transplantation (DAIT). These efforts include the long-standing TB Research Units, which currently focus on paucibacillary stages of TB latency and persistence; the Immune Mechanisms of Protection Against Mtb (IMPAc-TB) program and several other programs focused on advancing the development of a TB vaccine; the Feasibility of Novel Diagnostics for TB (FEND for TB) program, which evaluates early-stage diagnostics and novel diagnostic strategies in TB endemic settings; and the TB Research Advancement Centers to foster the next generation of tuberculosis (TB) researchers, which provides focused mentoring and funding support for new investigators, among other activities. Finally, Dr. Ison reported on DMID support to better understand and address non-TB mycobacteria (NTMs), which is a growing concern.

FY 2025 DMID Concepts Presented for Clearance

The following concepts were presented to the Subcommittee:

Feasibility of Novel Diagnostics for TB in Endemic Countries (FEND for TB) – The objective of this concept is to support the evaluation of early-stage diagnostics and novel diagnostic strategies for tuberculosis (TB) in the context of existing clinical diagnostic algorithms in TB endemic countries. The DMID Subcommittee recognized the importance of developing improved diagnostics for TB, particularly for use at the point of care. They recognized that it is important to test early-stage TB diagnostic technologies in a real-world situation and to consider the needs and priorities for TB diagnosis in the regions where diagnostics will be used and evaluated. The Subcommittee noted that there are a number of suitable TB diagnostics technologies that are in the pipeline to evaluate. The Subcommittee recommended that a well-defined structure be provided for what applications should include in response to the notice of funding opportunity and that applications should articulate the diagnostic priorities for regions where technologies are evaluated. They also recommended that partners in industry be encouraged to collaborate to ensure new diagnostic tests are likely to move forward to commercialization. The Subcommittee approved the concept with a unanimous vote.

Halting Tuberculosis (TB) Transmission – The objective of this concept is to advance understanding of where, when, and how TB transmission occurs, as well as support the development of tools and strategies to reduce transmission. The DMID Subcommittee expressed overall support for the concept and recognized the importance of understanding the key drivers of TB transmission for developing interventions to prevent the spread of TB. They recognized that there are a number of unknown aspects of TB transmission particularly with respect to the role of subclinical and asymptomatic TB. A Subcommittee member expressed some skepticism regarding the feasibility of addressing subclinical or asymptomatic TB if studies demonstrate these disease states are a major source of transmission. Program noted that the outcomes of studies would be important to inform TB control policies, even if the outcomes provide information on strategies that would not be feasible to implement. Furthermore, Program confirmed that international studies are required, since the United States does not have sufficient numbers of TB cases to support these studies. Another Subcommittee member asked Program to elaborate on proposed high burden settings. Program clarified that this would be TB endemic areas and include healthcare facilities, prisons, and other congregate areas in endemic countries. Lastly, another Subcommittee member asked why a set-aside initiative is needed. Program explained that a set-aside initiative is needed given the complexity of the proposed research program and level of funds needed for investigators to adequately respond. This approach will help DMID address the highest priority research questions in transmission. The Subcommittee approved the concept with a unanimous vote.

Partnerships for the Development of Tools to Advance Therapeutic Discovery for Select Antibiotic-Resistant Gram-Negative Bacteria – The objective of this concept is to advance the discovery and development of new antibiotics against multidrug resistant Gram-negative bacteria, including Acinetobacter baumannii, Enterobacterales, and Pseudomonas aeruginosa, to combat antimicrobial resistance (AMR), a top threat to public health and a priority across the world. The Subcommittee agreed that the research supported by this concept likely would lead to the development of novel tools to remove bottlenecks and facilitate Gram-negative antibiotic discovery and development. The Subcommittee approved the concept with a unanimous vote.

Promoting Innovative Research in Treponema pallidum Pathogenesis – The objective of this concept is to capitalize on recent advances in in vitro culture and genetic manipulation of T. pallidum to support exploratory research projects that improve our understanding of T. pallidum bacterial pathogenesis. The DMID Subcommittee recognized the importance of this concept and agreed that one way to address this public health need is through robust support for basic research. Historically, this area of research has been stymied by an expensive and complex animal model combined with a lack of genetic tools, thus contributing to a shortage of new and established investigators in the syphilis field. The Subcommittee noted that in other fields where recent advancements led to the ability to do genetic studies on genetically intractable organisms, there was a rapid increase in researchers and advancements in the respective fields. The Subcommittee suggested ways to focus the proposed funding opportunity, including language that encourages mentoring of young investigators and language that indicates possible sources of strains, biomaterials, and reagents to encourage newer investigators, which Program acknowledged. The Subcommittee was enthusiastic about this concept and approved it with a unanimous vote.

VI. Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)–Carl Dieffenbach, Ph.D., Director, DAIDS

Welcome and Approval of Minutes

Carl Dieffenbach, Ph.D. (Acting Chair)

Dr. Dieffenbach welcomed everyone and the ARAC members to the virtual meeting. The ARAC Chair, Dr. Elaine Abrams, was unable to attend the meeting due to a conflict because of the NIAID change in Council meeting date. The Committee approved the minutes of the September 11, 2023 meeting.

Director’s Report and SBIR Contract Topics

Carl Dieffenbach, Ph.D.

Dr. Dieffenbach acknowledged the passing of Dr. Ada Adimora who served on the NIAID Council and the ARAC from 2011 to 2015. There are four ARAC members rotating off the Committee. This meeting was the last ARAC meeting for Drs. Monica Gandhi, Paul Goepfert, Audrey Pettifor, and Ms. Melissa Turner. Dr. Dieffenbach thanked them for their contributions to the Committee. Dr. Dieffenbach introduced Dr. John T. Brooks who attended as the acting liaison from the CDC for this meeting.

In terms of leadership activities at the NIH, Dr. Bill Kapogiannis stepped down as acting Office of AIDS Research (OAR) Director in December 2023. He is currently at BARDA serving in the Office of the ASPR at HHS. Dr. Diana Finzi, Director of the DAIDS Basic Sciences Program, is the Acting OAR Director and is filling in until a permanent OAR Director is hired. Rear Admiral Dr. Timothy Holtz, OAR Deputy Director, is retiring on April 1.

There will be a change in leadership at the White House Office of National AIDS Policy, as Mr. Harold Phillips is retiring.

Within DAIDS, Mr. Brendan Cole is the new Chief of the Workforce Operations, Communications, and Reporting Branch in the DAIDS Office of the Director.

Budget Update

The House and Senate are working to reach agreement on the FY 2024 annual appropriation, and we are operating under a continuing resolution (CR). The expectation is that we will end up with a relatively flat budget. It is currently unknown what is in the President’s budget for FY 2025, and when it will be released.

NIAID FY 2024 Interim Financial Management Plan

Key points:

• R01 Payline: Established PIs are at the 8^th percentile. New PIs are at the 12^th percentile.
• Noncompeting or competing grants: NIAID will fund at 90 percent of approved and committed funding levels with no adjustments to fellowship (F), training (T), career development (K), and small business (SBIR/STTR) awards.
• Competing research initiatives could be cut up to 30 percent, with an estimated success rate between 18 and 22 percent for the entire Institute.

Scientific Update

Dr. Dieffenbach reflected on an event in December where DAIDS received the Partnership Award for Advancing CAB-LA for PrEP from the Global Health Technologies Coalition. This was an acknowledgment of the work that DAIDS as a whole performed with the clinical trials networks in collaboration with ViiV to make sure that we accomplished the HPTN 083 and 084 studies, bringing cabotegravir to a point where it was demonstrated in both studies to be superior to daily oral PrEP.

Small Business Innovative Research (SBIR) Contract Topics

SBIR money is a Congressionally mandated set-aside that comes off the top of the NIH budget, running 2.5 percent per year. Three contract topics (one reissue topic and two new topics) for the PHS 2024 solicitation to be published later this year were presented for committee approval:

1. Rapid Diagnostic Assays for Self-Monitoring of Acute or Rebound HIV-1 Infection (Reissue): To develop low-cost, rapid diagnostic assays to enable untrained individuals to test for HIV-1 during the earliest stages of initial infection or during loss of viral suppression in chronic treated infection.
2. Devices and Materials to Deliver Broadly Neutralizing Antibodies (New) (modified from ARAC January 2023): To support the development of devices and materials for the administration of bNAbs and bNAb derivatives primarily against HIV, but also RSV, malaria, HSV, Ebola, and Nipah virus.
3. New Drug Classes with Novel Mechanisms of Action for HIV, Hepatitis B, and Tuberculosis (New): To support development of new drug classes for HIV, HBV, or Mtb therapy with a different mode of action than FDA-approved drugs currently in use.

NIH Office of AIDS Research (OAR) Report on Workshop: Community Voices - Forging the Path Forward for HIV Self-Testing and Personalized Viral Load Monitoring

Lis Caler, M.Phil., Ph.D., David Chang, Ph.D.

On November 1 and 2, 2023, OAR hosted a workshop on HIV self-testing and personalized viral load monitoring. The meeting agenda was developed in consultation with HIV community partners to ensure priority topics to the community were woven into the discussions. The workshop provided a unique forum to discuss cutting-edge HIV diagnostic technologies and understand the FDA perspectives on the regulatory guidance involved in the process of making these products available to end users.

To bridge current challenges and gaps in access to HIV diagnostics and viral load testing in the United States, community leaders at the workshop agreed on the following needs: clarification, in practical terms, about different levels of "Undetectable" HIV viral load with regard to newer, more sensitive diagnostic technologies; incorporation of a geopolitical perspective on policies governing HIV self-testing and viral load monitoring; consideration of ways to address social determinants of health and improve access to prevention and care; and sustainable funding models for technology development, regulatory approval, and implementation.

In closing the workshop, Mr. Harold Phillips, Director of the White House Office of National AIDS Policy, noted that the HIV community is committed to improving health outcomes for people impacted by HIV by expanding access to at home and point-of-care HIV self-testing and viral load monitoring.

NIAID/DAIDS Programmatic Overview: Key Accomplishments and Future Directions

Therapeutics Research Program

Peter S. Kim, M.D., Director, TRP

The Therapeutics Research Program (TRP) was extensively reviewed, TRP staff was acknowledged, and new staff appointees were noted. The mission of TRP was stated which is to improve the health of people living with HIV (PLWH) by: developing new and improved therapeutics and diagnostics and advancing associated strategies to achieve durable viral suppression and ART-free remission, and addressing co-infections and comorbidities with greatest impact on the health of PLWH.

Activities for the TRP are generally weighted towards clinical trials and comprises almost 90 active clinical trials or trials in development. The clinical trials range from small pilot HIV cure studies through HIV treatment, larger phase 2B and phase 3 studies in tuberculosis, hepatitis, trials in inflammation and other comorbidities of HIV, diagnostics, and then our pandemic response trials on COVID-19 and Mpox. TRP, in collaboration with the DAIDS Basic Sciences Program (BSP) maintains resources to advance promising therapeutic candidates from the bench to clinical trials.

Recent advances, ongoing activities, and anticipated priorities were presented in the following areas: HIV and HIV-associated comorbidities, Tuberculosis, Hepatitis, and Pandemic Response.

Long-Term Goals: New/Improved Treatments and Associated Strategies, Point-of-Care and Home-Based Diagnostics, Strategies for Cure, and Address Key Comorbidities through Collaborations.

TRP is working to build partnerships and a portfolio of research to ensure advancement of promising long-acting technologies for the benefit of all PLWH.

Developing and testing novel strategies for HIV Cure including bNAbs and therapeutic vaccines is a high priority.

A summary of the REPRIEVE trial noted that participants with HIV infection who received pitavastatin had a lower risk of a major adverse cardiovascular event than those who received placebo.

Dr. Kim provided an overview of key HIV Cure studies opened to enrollment in 2023 and HIV Cure studies planned to open in Africa in 2024.

In collaboration with the ACTG and partner institutes and centers (ICs), TRP is working to identify and test interventional strategies to mitigate the impact of HIV infection on immune dysfunction and aging.

TB is globally the leading cause of morbidity and mortality for persons living with HIV. Even when persons with HIV are virally controlled, it's known that they still have a greater risk of morbidity and mortality from TB than the general population. TRP has a broad portfolio of preclinical and clinical research, and we need to fully understand TB-HIV pathogenesis.

We are hoping to better understand the early events of latent TB, also of TB disease, and to use that knowledge to identify targets for host-directed therapies for treatment.

A recent clinical trial that we were able to help fund was the LASER-TBM trial. TB meningitis is a disease that has a very high death rate which really underscores the need for better therapeutic regimens for TB meningitis, especially among those infected with HIV.

Hepatitis B and C combined is actually the second-leading cause of morbidity and mortality among those suffering from HIV. For PLWH, untreated HBV and HCV promotes rapid progression of liver disease, hepatocellular cancer, and untimely death. An estimated 10 to 20 percent of the 37.7M PLWH are co-infected with HBV and HCV, and this is an area that we will focus on to grow our portfolio in the coming years.

In 2020, as part of the pandemic response, DAIDS was charged by NIH leadership to undertake a series of trials to identify safe and efficacious therapies for the outpatient treatment of COVID-19 and human Mpox disease. We're starting to see the benefit of all the efforts that were put in.

Prevention Sciences Program

Sheryl Zwerski, DNP, Director, PSP

The Prevention Sciences Program (PSP) overview covered:

• Program Orientation
• 2023 Accomplishments
• Current and Future PSP Goals/Focus and Challenges

Program Orientation

• The four PSP branches were introduced, ranging from the preclinical branch and three clinically focused branches. PSP personnel changes to the program were noted.
• High-level priorities of the PSP included: development of HIV prevention products; further understanding of the biology of HIV susceptibility; improve engagement of key populations of both women and men; improvement of HIV treatment and prevention in pregnant women and children; optimizing strategies to diagnose, treat and prevent TB in the maternal and pediatric populations; and evolving the cure research in infants and children.
• Current PSP programs and initiatives were summarized.
• A summary was provided of the Resources to Advance Pediatrics and HIV Prevention Science (RAPPS) contract which serves as a platform to provide gap filling services as we move along from the preclinical through the later clinical testing stages.
• PSP oversees two HIV/AIDS clinical trials networks: HPTN and IMPAACT.

2023 Accomplishment Highlights

Much of PSP’s accomplishments are in partnership with colleagues across DAIDS, other NIH ICs (e.g., NICHD, NIMH, and NIDA) and many external partners including the clinical trials networks and industry partners.

• European Medicines Agency (EMA) approval of CAB-LA for PrEP in individuals 35kg and above based on HPTN 083 and HPTN 084 study data and successful GCP site and DAIDS sponsor inspection.
• Recognized as part of the Global Health Technology Coalition Award for Innovative Partnerships for ViiV/DAIDS partnership to conduct HPTN 083 and HPTN 084 resulting in approvals in United States, EU, Australia, and multiple African countries.
• Development of pediatric formulations: the Resources to Advance Pediatrics and HIV Prevention Science (RAPPS) contract, awarded in April 2023, serves as a platform to provide gap filling services as we move along from the preclinical through the later clinical testing stages.
• Both EU and U.S. FDA regulatory approvals for once-daily fixed dose, pediatric combination of abacavir/dolutegravir/lamivudine (Triumeq PD) for the treatment of children living with HIV.
• Prevention and Treatment for Pregnant Women: completion of enrollment in MTN-042 (Dapivirine ring and oral PrEP in pregnant women); presentation of primary results of MTN-042 (cohorts 1 & 2) and MTN-043 at CROI 2023; publication of the primary results from MTN-034 and MTN-042 cohorts 1 & 2; regulatory approvals for Remdesevir (Veklury) use during pregnancy, based on data from study IMPAACT 2032.

Current and Future Focus of PSP Research

• Major Goal: Pregnant women and children have access to treatment and prevention products on par with nonpregnant adults in shorter timeframe than currently exists.
• Children are less likely to be virally suppressed compared to adults due to multiple factors.
• Globally, PrEP use trails behind the estimated need.
• Women in the United States and globally need prevention options and PSP is working with investigators and industry to ensure inclusion in development of newer products for HIV prevention.
• Adolescents globally are in need of HIV prevention and treatment options that can be delivered in an engaging manner. The MTN-034 Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) study was a crossover trial where adolescent girls and young women were randomized to either oral PrEP or the dapivirine ring for 6 months, second 6 months, of course the crossover, and then the third 6 months was a choice period where participants could choose oral PrEP, the dapivirine ring, or no product at all. This trial was a great example of how to do research in adolescents and there were many lessons learned. Upshot of the results is that most young women chose one or the other, and the majority more than not chose the dapivirine ring in this study.
• Sustainable engagement of Black and Latino MSM in HIV prevention is challenging due to structural determinants and healthcare inequities. We have some unique opportunities through NIMH collaboration and HPTN to make strides in this area.
• Through our collaborations with NIMH, partnerships, solicited programs, and the HPTN- PSP is committed to better understanding of the biological and socio-behavioral issues that face transgender people.
• Opioid users need options that are easy to use/adhere to and as such developing strategies that meet those needs are a focus for PSP as part of the collaboration with NIDA and the HPTN. 
• Meeting the needs of maternal/child populations for TB prevention and treatment will continue to be a high priority.

Challenges

• Challenges abound, how do we continue to improve options when the field has changed, and resources are not infinite?
  • Success is great and makes future research more complex-
    • What advantage does a potential new product have over current?
    • Trial methods that are feasible are necessary.
• The work we invest in ultimately needs to have the potential to be impactful for key populations in the area of HIV prevention and treatment.
  • What will we do with the information once we have it?
  • Does the work change clinical practice and/or guidelines?

Summary of Specific Aims of PSP’s Clinical Trials Networks: HPTN, IMPAACT

HPTN: Novel ARV-based HIV prevention methods and delivery systems; longer duration ARVs; Multipurpose Prevention Technologies (MPTs); integrated biomedical and socio-behavioral prevention strategies.
IMPAACT: Novel and durable interventions for treatment of HIV; complications and co-infections; ART-free remission; Tuberculosis prevention and treatment.

Basic Sciences Program

Jason Hataye, M.D., Ph.D., Deputy Director, BSP

The presentation began with an overview of the Basic Sciences Program (BSP), followed by the following HIV Research Highlights and Future Directions:

• Structural Dynamics of HIV-CD4 binding
• B Cell Engineering for Broadly Neutralizing Antibodies
• Epidemiology and HIV Treatment
• Scientific Workforce Diversity

Overview of the BSP

• BSP personnel changes to the program were noted.
• BSP mostly supports early-stage science, specifically the early indications of what might eventually be important breakthroughs. The foundations are in a large number of unsolicited grants, but BSP also solicits grants in order to indicate the direction in areas of particular need. BSP collaborates with other DAIDS programs (Therapeutics, Prevention and Vaccines) and BSP’s role is to generate new ideas to advance HIV treatment and prevention.
• Collectively, BSP oversees over 570 projects with an annual budget of $436 million.
• The primary focus in the Pathogenesis and Basic Research Branch is on mechanistic work with particular attention to latency, persistence, and cure.
• In the Targeted Interventions Branch, there is an increased focus on non-traditional therapeutics such as gene and cell-based therapies, biologics, and RNA therapeutics. BSP also continues to work on specific interventions to validate HIV targets and small molecule inhibitors.
• The Epidemiology Branch focuses on HIV outcomes in large cohorts throughout the world. The Epi Branch has also expanded support of new surveillance approaches, such as identifying people who are at particularly high risk of infection.
• Through collaboration and alignment between federal agencies to fund implementation research, BSP coordinates many stakeholders to end the HIV epidemic.

HIV Research Highlights and Future Directions

Structural Dynamics of HIV-CD4 binding - Implications and Future Directions

1. Informs structure-based design of interventions that interdict these intermediate steps, including drugs and vaccines.
2. Structural concurrence stemming from the two methods strengthens the rationale for using SOSIP trimers as immunogens in vaccine studies.
3. To CD4 and Env trimer, add co-receptor for a complete atomic-level movie that models the dynamics of HIV binding and membrane fusion.
4. Molecular dynamics simulations can fill gaps and define the thermodynamics and kinetics of inter-protomer cooperativity.
5. These projects are a model of collaboration and demonstrate the value and role of the HIV structural centers in the context of unsolicited R01 funding.

B Cell Engineering for Broadly Neutralizing Antibodies against HIV

1. Optimizing site-specific editing and reducing off-target editing.
2. Approaches to express multiple bNAbs.
3. Reducing vector-induced immune responses.
4. Improving specific transduction of B cells.

Epidemiology and HIV Treatment

The International epidemiology Databases to Evaluation AIDS (IeDEA) consortium includes 7 regional data center awards, which leverage clinical, research, and epidemiologic data to monitor and guide the response to the HIV/AIDS epidemic. IeDEA's research agenda is broad, with co-funding by nine ICs. In the coming year, we will seek to renew the IeDEA consortium for a fifth cycle. The Research Scope involves long-term impact of HIV and its treatment; co-infections (hepatitis and tuberculosis); comorbidities such as cancer, organ disease, mental health and alcohol and substance use; and research across the age span from birth to elderly.

IeDEA is focused on data pipelines, not static data repositories. Most data come from normal clinical care at facilities that range from basic rural clinics to tertiary care facilities. Prospective data are also collected under the Sentinel Research Network protocol and include more intensive measures of co-morbidities. There is also a global population cohort of tuberculosis patients which works closely with TB-RePORT. IeDEA is also a platform for grants.

One research area where IeDEA has contributed is on the safety, uptake, and long-term effectiveness of Dolutegravir.

Scientific Workforce Diversity

The NIH Centers for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI) program was highlighted. The goal of the program is to increase the participation of underrepresented communities in the fields of HIV science and medicine. Scholars participating in the initiative receive educational and professional training at various academic levels including high school, undergraduate, graduate, and post-doctoral. CDEIPI supports the development of new programs and the enhancement of existing programs within the CFAR network in collaboration with Independent School Districts, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions throughout the United States.

A snapshot was provided of one effort- CDEIPI funding at Johns Hopkins enabled them to launch a Summer Health Disparity Scholars Program, leveraging their successful Generation Tomorrow initiative. They attract college students from across the United States interested in HIV and HCV health disparities and social determinants of health. Scholars can receive counseling, training, participate in a lecture series and mentored research, and learn best practices for outreach into their communities. Training is conducted in collaboration with the Maryland Department of Health and a local Baltimore community partner, Sisters Together and Reaching, Inc.

Vaccine Research Program

Jim Lane, Ph.D., Acting Director, VRP

The overall programmatic update for the Vaccine Research Program (VRP) covered: VRP Mission and Organization; HIV-1 Vaccine Strategy, Discovery, and Design; Vaccine Concepts in Clinical Testing; and Future Directions for Vaccines.

VRP Mission and Organization

The VRP supports biomedical research to reduce HIV incidence through the development of effective biomedical research strategies, including vaccines that are safe, effective, and durable.

VRP is comprised of three branches that interact to achieve this: Vaccine Translational Research Branch (VTRB), Preclinical Research and Development Branch (PRDB), and Vaccine Clinical Research Branch (VCRB).

VRP Goals - Preclinical work is involved in the design, development, and evaluation of potential HIV/AIDS vaccines for the prevention of HIV infection and/or disease; translational work advances promising candidates for manufacturing into clinical for testing; clinical work evaluates candidate vaccines by participating in the design, development, and conduct of phase 1, 2, and 3 trials.

Last year, Katalin Karikó and Drew Weissman, were awarded the 2023 Nobel Prize in Physiology or Medicine for discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19. Their findings published in 2005 represented a major change in understanding of how cells recognize and react to different forms of mRNA, and two of the grants acknowledged in that paper that supported this work were from DAIDS.

VRP key scientific initiatives/programs were briefly summarized, including Consortia for HIV/AIDS Vaccine Development (CHAVD), HIV Vaccine Research and Design (HIVRAD), Innovation for HIV Vaccine Discovery (IHVD), Integrated Preclinical/Clinical AIDS Vaccine Development Program (IPCAVD), and the HIV Vaccine Trials Network (HVTN).

HIV Vaccine Strategies
HIV Broadly Neutralizing Antibodies (bNAbs)
Data supporting feasibility for bNAb vaccine-

• bNAbs prevent HIV infection in humans: Ab Mediated Protection Study (AMP)
• Germline targeting vaccination induces HIV broadly neutralizing Ab precursors

HIV-1 Envelope Sites of Vulnerability
Gp120-gp41 interface, CD4-binding site, V2 glycan, V3 glycan, fusion peptide, member proximal external region (MPER).

VRP supported research accomplishments in 2023 were summarized.

• HVTN 703/4 HPTN 081/085 (the AMP trials) demonstrated proof of principle that bNAbs protect individuals from HIV infection by sensitive viruses.
• Development of multiple knock-in mouse models for testing bNAb inducing immunogens.
• Priming immunogens designed and tested in animals to engage four bNAb target sites.
• Boosting immunogens designed and tested in animals.
• More than 11 experimental phase 1 trials initiated (or soon to be initiated) to investigate these new immunogen designs and regimens.
• Escalating fractionated dosing shown to promote GC development and SHM under study in HVTN 301 and HVTN 144.
• Shift to mRNA clinical trial vaccine manufacture of HIV envelope immunogens.
• Development of two novel adjuvants (SMNP and empty LNPs) for clinical use.

HIV Vaccine Development Gaps were outlined.
Proof of Concept for Induction of bNAbs by Immunization

• Design, GMP manufacture and evaluation in preclinical models of additional priming and boosting immunogens.
• Optimize the dynamics of germinal center (GC) maintenance and boost timing.
• Understand how to drive/guide SHM/affinity maturation of multiple bNAb lineages.
• Harness technology to combine primes and boosts in simplified or single shot regimens.
• Proof of concept in a phase 1 clinical trial that at least one bNAb lineage can be started and guided to at least 50 percent breadth.

Definition of the Rules for Prime and Boost Immunogen Design

• Understanding the interplay between the frequency/affinity of target B cells (precursor or partially mature bNAb B cells) and immunogen avidity, affinity, and dose to rationally select priming and boosting immunogens.
• Understanding the rules for affinity gradients between priming and boosting immunogens to recruit target B cells vs competitor B cells in the GC to select SHM and drive bNAb maturation.
• Understanding the dynamics of germinal center (GC) maintenance and boost timing.

Fostering Durability of the Immune Response

Highlights of recent clinical trials were presented, including ongoing phase 1 studies.

In a Nature Medicine article highlighting 11 clinical trials that will shape medicine in 2024, the HVTN 142 FIH CMV-HIV Vaccine (VIR-1388) was noted. It is intended to induce strong and sustained T cell responses that can potentially prevent acquisition of HIV.

The HIV antibody portfolio was reviewed.

Future directions for vaccines were summarized.

A summary of the highlights of an August 2023 workshop entitled "T and B Cell Synergy for HIV Vaccines," was presented.

Ballot Voting Outcome:
All three of the SBIR Contract Topics were unanimously approved by the Committee.

Public Comments: None

VII. Adjournment

The meeting of the Council adjourned at 4:19 p.m., on Tuesday, January 30, 2024.

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.