NIAID Council Minutes September 11, 2023

The 205^th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened at 5601 Fishers Lane in the Grand Hall at 10:30 a.m. on Monday, September 11, 2023. Dr. Hugh Auchincloss, Acting 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 11:35 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 11:40 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 Acting Director, NIAID-Hugh Auchincloss, M.D.
III. Guest Speaker—Ted Pierson, Ph.D., Director, Vaccine Research Center, NIAID
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 3,795 research and training applications with primary assignment to NIAID for a requested amount of $1,206,298,409 in first-year direct costs and recommended approval of 1,917 applications with $704,694,700 in first-year direct costs.

II. Remarks of the Acting Director, NIAID—Hugh Auchincloss, M.D.

Dr. Auchincloss opened the Council session by welcoming visitors to the meeting. He also introduced three ad hoc members: Dr. Annette Jackson, Associate Professor of Surgery and Associate Professor of Integrative Immunobiology, Duke University School of Medicine; Dr. Effie Wang Petersdorf, Professor, Clinical Research Division and Madeline Dabney Adams Endowed Chair in AML Research, Fred Hutch Cancer Center; and Dr. Robert Montgomery, Director, Transplant Institute NYU Langone Health.

Dr. Auchincloss acknowledged the contributions of five retiring Council members and thanked them for their service.

Consideration of Minutes of Previous Meeting

Council considered the minutes of the June 5, 2023 meeting and concepts that had been presented and approved them as written.

Staff and Organizational Changes

Meetings and Events

On May 16, 2023, NIH held a groundbreaking ceremony for the new Clinical Center wing, which will be for Surgery, Radiology, and Laboratory Medicine.

NIH issued a request for information soliciting feedback on the NIH Mission Statement. The deadline to respond is November 24, 2023.

The White House Office of Science and Technology Policy is seeking input on potential changes to research oversight policies for Dual Use Research of Concern (DURC) and Potential Pandemic Pathogen Care and Oversight (P3CO). Responses need to be submitted by October 16, 2023.

On June 13, 2023, NIAID representatives met with Genessa Giorgi, the incoming HHS Health Attaché to India, to discuss NIAID activities and priorities in India.

On June 20, 2023, Dr. Auchincloss and Deputy Director-General Xu Jie, Chinese Ministry of Science and Technology (MOST), co-chaired the virtual China MOST-NIH Infectious Diseases Technical Exchange, which focused on influenza vaccine, diagnosis, and treatment strategies.

Budget Update

Legislative Update

Dr. Auchincloss thanked NIAID staff who participated in briefings for members of Congress and their staff on the topics of grant oversight, Long COVID research, and Project NextGen.

Other Information Items

Dr. Auchincloss presented the latest COVID-19 data on new hospital admissions and weekly COVID-19 deaths in the United States, along with the status of the updated COVID-19 vaccines for the fall. The White House launched Project NextGen, which is a partnership between NIAID and the Biomedical Advanced Research and Development Authority (BARDA). NIAID’s role is to initiate clinical trials to evaluate mucosal and broadly protective vaccines.

Next, Dr. Auchincloss gave an update on HIV/AIDS. PEPFAR, which celebrated its 20^th anniversary in 2023, is one of the most successful public health programs of all time. When PEPFAR began, only 50,000 people in sub-Saharan Africa were receiving treatment; it now supports 65 million people with HIV treatment and testing services. Unfortunately, funding to continue the program is in jeopardy.

He presented promising data showing the HIV incidence in the United States is slowly going down, which may be a result of the Ending the HIV Epidemic (EHE) initiative that was launched in 2019. The goal of the EHE program is to reduce HIV infections by 90 percent by 2030. Dr. Auchincloss then highlighted promising results from two HIV studies that were recently published in scientific journals.

Dr. Auchincloss summarized NIAID-supported medical countermeasures that are progressing through clinical activities. NIAID research laid the foundation that led to FDA-approved respiratory syncytial virus (RSV) interventions for various vulnerable populations. In NIAID’s Division of Intramural Research, an RSV vaccine candidate is being tested in children. The anthrax vaccine, CYFENDUS, was approved by the FDA. A dengue vaccine candidate is in Phase III clinical trials in Brazil and India. Two universal influenza vaccine candidates are in Phase I clinical trials. A tuberculosis vaccine candidate has advanced to a Phase III clinical trial. A chikungunya vaccine candidate performed well in a Phase III clinical trial. A Phase I clinical trial of Vaccine Research Center’s Sudan ebolavirus vaccine candidate was completed. A malaria monoclonal antibody performed well in a Phase II clinical trial in Mali, showing 88 percent efficacy in preventing infection after a single shot.

He concluded by noting the FDA approved a treatment for CHAPLE Disease, DMID made five awards to study Post-Treatment Lyme Disease Syndrome, a longitudinal study that began widespread screening and early treatment of newborns for Severe Combined Immunodeficiency boosted survival rates, and a few recent successes in transplantation research.

III. Guest Speaker—Ted Pierson, Ph.D., Director, Vaccine Research Center, NIAID

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

Dr. Rotrosen welcomed the subcommittee members to the 205^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

Adora Lin, M.D., Ph.D., FAAAAI., Dr. Lin joined the Allergy, Asthma, and Airway Biology Branch as a Medical Officer in the Food Allergy, Atopic Dermatitis, and Allergic Mechanisms Section in June 2023. Prior to joining DAIT, Dr. Lin received her M.D. and Ph.D. from the University of Cincinnati College of Medicine in 2010. She completed an internship and residency in Pediatrics at Children’s National Hospital, followed by a fellowship in Allergy and Immunology at NIAID. She joined the faculty at Children’s National and the George Washington University School of Medicine and Health Sciences in 2017, where her research focused on the role of B cells and regulatory B cells in the development of food allergy and allergic asthma.

Matthew A. Sherman, M.D., Dr. Sherman joined the Autoimmunity and Mucosal Immunology Branch as a Medical Officer in the Autoimmune and Primary Immunodeficiency Diseases Section in July 2023. Dr. Sherman completed his fellowship in pediatric rheumatology in a joint program between Children’s National Hospital and NIAMS, where he investigated clinical phenotypes of autoantibodies in the juvenile idiopathic inflammatory myopathies. During his fellowship, he co-led the Childhood Arthritis and Rheumatology Research Alliance Juvenile Dermatomyositis Therapeutics Workgroup and earned a Master of Health Sciences in Clinical Research from Duke University’s Clinical Research Training Program. Dr. Sherman received his undergraduate degree from Columbia University in New York and attended University of Michigan Medical School. He completed his pediatric residency at Children’s National Hospital in Washington, DC.

Selected Funding Opportunities

NIAID

NOT-AI-23-037: Notice of Special Interest (NOSI): Administrative Supplement for Collaborative Projects Supported by the NIAID RNCP and CCRP. The purpose of this notice is to highlight NIAID’s interest in supporting research aimed at a collaboration between recipients funded by the Radiation and Nuclear Countermeasures Program (RNCP) and the Chemical Countermeasures Research Program (CCRP). These collaborations between RNCP- and CCRP-supported researchers will generate data that can be leveraged for new medical countermeasures (MCMs) discovery and early development and enhance the state-of-the-science in both research areas.

Broad Agency Announcement (BAA-75N93022R00021): Development of Radiation/Nuclear Medical Countermeasures (MCMs) or Biodosimetry Devices. The goal of this BAA is to solicit proposals for (a) the development of MCMs against radiation injury or (b) biodosimetry approaches targeting radiation-specific biomarker identification and/or device development to predict acute and/or delayed damage to specific organs and tissues beyond dose assessment. The BAA is intended to support research and development of promising new approaches to mitigate or treat tissue injuries arising from unintended exposure to ionizing radiation, which may include biologics (e.g., cytokines and free radical scavengers), cellular therapies, or drugs (e.g., anti-inflammatory agents, antibiotics, and anti-fibrotics).

NOT-AI-23-058: NOSI: Research on Early Allergy Determinants Using Biosamples from the SUNBEAM Birth Cohort. The purpose of this notice is to solicit applications proposing studies utilizing available biologic and environmental samples collected as part of the birth cohort study, Systems Biology of Early Atopy (SUNBEAM), NCT04798079, to discover and advance the understanding of novel and established clinical, environmental, biological, and genetic early-life factors in the development of allergic diseases. Studies using these samples are expected to give a deeper understanding of mechanisms contributing to the development of allergic diseases, disease endotypes, and will identify molecular targets for disease prevention.

Division Activities

Radiation and Nuclear Countermeasures Program (RNCP)

Radiation-Induced Cutaneous (CRI) and Gastrointestinal (GI) Injuries: Understanding Pathologies, Assessment, and Clinically Accepted Practices. From December 5 to 9, 2022, in Fontenay-aux-Roses, France, an in-person workshop was held at the Institut de Radioprotection et de Sûreté Nucléaire (IRSN), which is the French government agency responsible for radiation protection. Co-sponsored by the NIAID RNCP and the IRSN, the meeting brought together researchers and NIAID staff from the United States and IRSN researchers, as well as scientists from local French academic institutions, to discuss topics of mutual interest to both agencies. The goals of the workshop were to examine pathophysiology and clinical interventions for radiation-induced cutaneous (CRI) and gastrointestinal (GI-ARS) injuries; explore novel assessment approaches and medical countermeasures for CRI and GI-ARS; identify existing gaps, challenges, and needs for translational application in each space; and foster collaborative connections between the U.S. and French scientists. An outcome of the meeting was the initiation of several collaborations between French and U.S. investigators. A peer-reviewed commentary is also planned.

NIAID/AFRRI Annual Meeting. On November 4, 2022, NIAID/RNCP held an annual meeting for the NIAID/AFRRI-USUHS Interagency Agreement (IAA) that was originally established in 2005. The meeting was attended by NIAID/DAIT and AFRRI/USUHS leadership and scientific staff. The IAA consists of five separate work plans that focus on small and large animal model development and testing of medical countermeasures to treat radiation-induced injuries. The scientific updates included advancements and refinements of cutaneous and multi-organ injury models and performance of drug candidates. Discussion sessions addressed future research strategies and the identification of solutions to current logistical challenges.

2022 Annual Update Meeting for the Centers for Medical Countermeasures Against Radiation Consortium (CMCRC). On January 10 and 11, 2023, the CMCRC held a hybrid (in-person/virtual) annual meeting at the University of Maryland School of Medicine (UMSOM) in Baltimore, Maryland. Each of the centers – UMSOM, Columbia University & Duke University – provided individual updates as well as reporting on collaborative research efforts between the centers for the FY 2022 funding period. The meeting offered an opportunity to showcase the portfolio to other key stakeholders from partner federal government agencies (NCI, BARDA, NASA, DoD, and FDA). In addition, the meeting fostered dialog and collaboration among the CMCRC investigators and program staff regarding future research and development directions. Also present were four members of the External Advisory Board, who provided their insight and advice about the research discussed. It was well-attended with over 70 online and in-person participants.

Federal Roundtable on Potential Health Risks for Individuals Residing Near Nuclear Power Plants. Held on February 14, 2023, this virtual meeting was convened in response to inquiries made by several members of Congress to the Secretary of the Department of Health and Human Services. Organized by an NIH planning committee that included the NIAID RNCP Director, NCI, and NIEHS, the event was a coordinated federal discussion about potential health risks for individuals residing near nuclear power plants. Current estimates of radiation exposures to residents in areas surrounding nuclear power plants are very low, but it is possible that exposures from several decades ago were potentially higher. The goal of the Roundtable was to respond to the Congressional inquiries by convening an interdisciplinary group of experts to address this topic. A meeting summary from the event, which involved more than 30 U.S. government radiation subject matter experts and included recommendations, was delivered by the NIH-OD to the HHS Secretary in late March 2023.

Immune Dysfunction U01 Consortium Kickoff Meeting. On February 13, 2023, the Radiation-Induced Immune Dysfunction U01 consortium held its first meeting (all-virtual format). Each awarded PI provided an overview of his/her projects and participated in a brief Q&A as well an open discussion session to sum up their presentations. The NIAID ImmPort team also presented to the consortium on the utility of the data repository for their studies. This meeting served as an opportunity for the key personnel of the consortium to meet and become acquainted with one another’s work and areas of expertise. These early interactions will foster strong future collaborative interactions among the group and program staff. The meeting was well attended with >50 online participants.

NIAID-IRSN Dosimetry Protocol Harmonization and Exchange Meeting. On February 16, 2023, a hybrid meeting (in person/virtual) was held at Fishers Lane, Rockville, Maryland, to discuss strategies for improving radiation dosimetry reproducibility throughout the radiation biology research community. This meeting also included an effort to explore implementing an international radiation dosimetry exchange exercise between the Institut de Radioprotection et de Sûreté Nucléaire (IRSN) and the NIAID/RNCP dosimetry harmonization program. Attendees at the meeting included representatives of the ISRN dosimetry program, U.S. academic radiation biology and dosimetry experts, as well as Editors-in-Chief of two prominent peer-reviewed radiation journals. In addition to establishing agreement on dosimetry-protocol reporting requirements, the participants agreed to author a commentary for simultaneous publication in both journals, highlighting the need for defined radiation dosimetry protocol reporting requirements in the literature. This commentary was published alongside new journal “Instructions to the Author” that incorporate new dosimetry reporting requirements.

2023 NIAID/NIDDK Intestinal Stem Cell Consortium (ISCC) Bi-Annual Update Spring Meeting. On March 21 and 22, 2023, the NIAID/NIDDK ISCC bi-annual meeting was held in a hybrid format (in-person/virtual) at Cedars-Sinai, Los Angeles, California. Each PI provided an update on the research conducted to date and collaborative topic areas. The purpose of this meeting was to allow researchers a chance to provide an update on the progress that has been made over the past year. The meeting helped foster dialog and collaboration among the ISSC investigators and program staff regarding future research and development directions. More than 60 participants were involved.

NIAID/BARDA Radiation Medical Countermeasures Radiation Portfolio Update Meeting. On April 24, 2023, a meeting was held between the RNCP and Biomedical Advanced Research and Development Authority (BARDA) staff. The purpose of these ongoing, semi-annual meetings is to provide programmatic transparency, ensure that the funded research programs are aligned across both HHS agencies, and provide advanced information on potential transition of promising candidates. Held at 5601 Fishers Lane, the hybrid meeting involved eight RNCP and 10 BARDA team members, with special discussions surrounding recent biosimilar FDA approvals and recently awarded RNCP product development contracts.

Allergy, Asthma, and Airway Biology Branch

None

Basic Immunology Branch

Human Immunology Project Consortium (HIPC). On June 7 and 8, 2023, the annual meeting of the HIPC program was held in Rockville, Maryland. This trans-NIAID program, led by DAIT, consists of a coordinating center and eight multi-project cooperative agreements (U19s), which are collecting detailed clinical data and conducting immune profiling on diverse human cohorts at steady state and in response to pathogenic infections or vaccines. The HIPC Coordinating Center fosters collaborative activities across HIPC, including managing an infrastructure and opportunity fund, to further develop and implement clinical and immunologic data standards, and maintain and expand a human immunology knowledgebase and analysis portal, ImmuneSpace (https://www.immunespace.org/).

Characterizing and Improving Humanized Immune System Mouse Models. On July 11, 2023, the annual meeting of the contract program to characterize and improve humanized immune system mouse models was held in Rockville, Maryland. The four groups reported progress on their projects to develop, optimize, and test the ability of non-fetal human tissues (cord blood hematopoietic stem cells, neonatal tissue) or porcine thymus tissue transplanted into mice to ensure reproducible immune reconstitution and maintenance in blood, lymphoid, and non-lymphoid tissues. Training sessions are being planned and will be hosted by each contractor to share knowledge and techniques for engraftment and characterization of humanized mouse models developed under this contract.

Cohort Studies to Improve Our Understanding of Influenza Immunity, Vaccine Response and Effectiveness in Older Adults. On July 12, 2023, the annual meeting of this program was held in Rockville, Maryland. The program is a partnership between the Division of Allergy, Immunology, and Transplantation and the Division of Microbiology and Infectious Diseases of NIAID. 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, through characterization of existing or new longitudinal cohorts. Three groups were awarded under this initiative: Jackson Laboratory (Duygu Ucar and George Kuchel), Dana-Farber Cancer Institute (Wayne Marasco), and Johns Hopkins University (Sean Leng and Jay Bream). Awardees presented their research progress from each of their cohorts during the first year. The meeting provided a forum for researchers to exchange ideas and to begin discussions for future collaborations.

Measuring and Predicting Reproductive Health: Advancing Technology and Fundamental Understanding in Maternal-Fetal Immunity Workshop. On July 13 and 14, 2023, a workshop was held at Fishers Lane, Rockville, Maryland, to assess current knowledge in the field on the role and function of the immune system during healthy pregnancy and adverse pregnancy outcomes; determine the potential of immune metrics and technologies to provide insight into strategies for reducing adverse pregnancy outcomes; and encourage communication and collaboration amongst immunologists, maternal-fetal medicine researchers and clinicians, and technology developers.

NIAID’s Collaborative Influenza Vaccine Innovation Centers (CIVICs). From August 6 to 9, 2023, the CIVICs Annual Meeting was held in West Palm Beach, Florida, with both virtual and in-person attendees. The CIVICs network, comprised of three Vaccine Innovation Centers, a GMP Manufacturing Core and two Clinical Trial Cores, is focused on design and testing of novel universal and improved seasonal influenza vaccines candidates. This year’s Annual Meeting focused on progress during the first 4 years of the program, including vaccine design strategies, preclinical data associated with candidates that have entered or will soon enter the GMP manufacturing pipeline, topline reports for a completed virus challenge study, updates on ongoing vaccine clinical trials, and plans for several new Phase I clinical trials under the CIVICs program. Information and news about CIVICs can be found at https://www.niaidcivics.org.

Immune Mechanisms at the Maternal-Fetal Interface. On August 29, 2023, the annual meeting of the Immunity at the Maternal-Fetal Interface Program was held via virtual platform. The program is composed of 11 R01 projects and is designed to determine the functional interactions of immune cells present at the maternal-fetal interface, including mechanisms that maintain a healthy pregnancy, responses to vaccinations or infections that protect or impact the fetus and those that may influence fetal immune system development. Investigators presented their progress and discussed collaborations that resulted from the program.

Maintaining Immunity After Immunization Annual Meeting. On September 7, 2023, the annual progress update for the Maintaining Immunity after Immunization program was held at the 5601 Fisher’s Lane conference center. The 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.

Transplantation Branch

HLA and KIR Region Genomics in Immune-Mediated Diseases. On June 16, 2023, 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. Current projects are 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. Consortium members shared their progress and discussed potential collaborative opportunities to improve accessibility and utilization of disease association data by clinicians and the broader research community, as well as the importance of validating findings in diverse cohorts and through molecular analyses. Attendees included consortium members and extramural staff from NIAID and co-funding institutes, NCI and NINDS.

Autoimmunity and Mucosal Immunology Branch

Mucosal Immunology Studies Team (MIST) Steering Committee. On June 12, 2023, the MIST steering committee convened its annual meeting in Philadelphia, Pennsylvania, to exchange information and share progress on U01 cooperative agreement projects supported by RFA-AI-20-027. Investigators representing each of the seven NIAID-supported U01 awards presented updates on their projects that collectively cover an array of topics, including host-commensal relationships, host defense, type 2 immunity, mucosal barrier biology, metabolic regulation, and neuro-immune interactions. Five early-stage investigators whose research is partially supported by the MIST Infrastructure and Opportunities Fund participated in the annual meeting and gave oral presentations on their ongoing mucosal immunity-related projects.

Development of Sample Sparing Assays (DSSA) for Immune Monitoring Program Annual Investigator’s Meeting. On June 1 and 2, 2023, the Development of Sample Sparing Assays for Immune Monitoring Program had their first in-person Annual Investigator Meeting at Fishers Lane, Rockville, Maryland. The investigators shared progress on their studies and developed a plan to share assays more broadly beyond NIAID (e.g., neonatology meetings). Investigators have developed assays that require smaller sample sizes and are more widely accessible in areas where healthcare disparities exist, either due to stability of the samples or cost.

Immune Drivers of Autoimmune Disease (IDAD), Kick-off Meeting. On June 26, 2023, investigators from the newly awarded IDAD Cooperative Research Program met in Rockville, Maryland, to discuss their research plans and potential areas of collaboration. The program supports three U01 projects from the University of Massachusetts Medical School, Oklahoma Medical Research Foundation, and the University of Texas Southwestern Medical Center. PIs funded under this program will work to define the immunologic states and dynamics that drive autoimmune disease in order to enhance our understanding of the immunologic processes, events, and changes that underlie the clinical manifestations of autoimmune diseases, including disease flare, remission, and progression of established disease, as well as the progression from a state of elevated risk to clinical diagnosis of autoimmune disease.

Autoimmunity Centers of Excellence (ACE), Steering Committee. On June 27 and 28, 2023, the ACE Steering Committee convened in a face-to-face meeting in Rockville, Maryland, to discuss the progress on their basic and mechanistic studies, as well as ACE-funded clinical trials. The ACE continues to be highly productive in supporting outstanding fundamental research into the mechanisms of autoimmunity in humans, and supporting clinical trials with mechanistic studies of novel therapies for autoimmune diseases, including immunoglobulin G4-related disease (NCT04918147), systemic lupus erythematous (NCT050482380, NCT05306873, NCT03093402), rheumatoid arthritis (NCT02603146), multiple sclerosis (NCT05285891), pemphigus (NCT03239470), and COVID vaccine responses in people with autoimmune disease (NCT05000216). This program has entered its last year of the current 5-year cycle, with a final face-to-face meeting scheduled for January 2024. New FY 2024 awards are projected for late spring of 2024.

FY 2025 Research Concept Clearances Presented to Division Advisory Council

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

1. Bat Immunology Network Research Projects (R01, Clinical Trial Not Allowed) The purpose of this notice of funding opportunity (NOFO) is to support research to characterize bat immune components and understand protective innate and adaptive immune mechanisms. A companion NOFO will support the development of reagents for use by the research projects.
2. Bat Immunology Network Research Resource Program (U24, Clinical Trial Not Allowed) The purpose of this NOFO is to support reagent development to facilitate research supported by a companion NOFO to characterize bat immune components and understand protective innate and adaptive immune mechanisms. The bat immune system is unusual and differs in important ways from other mammals. Understanding bat immunology will be important in determining the role of the bat as a vector. An appreciation of bat immunology may inform treatment strategies for human disease and allow for improved interpretation of pathogen studies that use the bat.
3. Development of Radiation Biodosimetry Assays and Devices (U01, Clinical Trial Not Allowed) This initiative will enable both early- and mid-stage research to accelerate the development of radiation biodosimetry assays and devices to rapidly assess radiation dose and to predict the consequences of immediate (days) and delayed (months to years) radiation effects to major organs in an individual.
4. Research Initiative for Vaccine and Antibiotic Allergy (UG3/UH3, Clinical Trial Not Allowed) The scientific objective of this initiative is to support new research in the field of antimicrobial and vaccine allergy, primarily focusing on the mechanisms of allergic reactions. During the UH3 phase, this initiative will enable investigators to produce data in support of their hypotheses.
5. Understanding Mechanisms and Outcomes of Trained Immunity (R01, R21, Clinical Trial Not Allowed) This initiative will encourage R01 and R21 projects that aim to define the immunologic mechanisms responsible for trained immunity/innate immune memory. This program will also support studies to determine how pre-existing innate immune memory impacts adaptive immunity and subsequent responses to vaccines or natural infections. The grants will be funded using NIAID payline dollars for investigator-initiated R01 and R21 grants.

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 September 11, 2023. She provided a DMID personnel update, recognizing new staff appointments made in the Division since the last Council meeting, including Christian Gonzalez, Respiratory Diseases Branch; Dr. Rachelle Smith, Virology Branch; and Dr. Will Sears, Office of Clinical Research Resources. She also noted the recent retirement of Virology Branch Chief Dr. Mark Challberg and reported that Dr. Jean Patterson would serve as the Acting Virology Branch Chief until a permanent replacement is appointed. Following staff introductions, Dr. Erbelding provided a report on recent activities of note:

• Appointment of Dr. Jeanne Marrazzo as the new NIAID Director. Dr. Erbelding noted that in a presentation to the DMID Subcommittee last year, Dr. Marrazzo shared her thoughts on urgent priorities in sexually transmitted infections in the United States. Dr. Erbelding briefly described Dr. Marrazzo’s areas of expertise, noting that Dr. Marrazzo has a strong interest in many of DMID’s scientific areas, and expressed her support for Dr. Marrazzo’s selection as NIAID’s new Director.
• COVID-19 Variant Immunologic Landscape (COVAIL) trial update. NIAID continues to publish on the results of the COVAIL trial, which is designed to compare many different combinations of bivalent and monovalent SARS-CoV-2 variant vaccines. She highlighted the results of a recent study published in Nature that shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly cross protective neutralizing antibody responses against diverse SARS-CoV-2 variants.
• Role of Deer in SARS-CoV-2 Transmission. Scientists supported under DMID’s Centers of Excellence for Influenza Research and Response program found that SARS-CoV-2 evolves to new variants three times faster in white-tailed deer than in people, noting the impact such transmission could have on SARS-CoV-2 evolution and spillover events.
• Oral Bait Lyme Vaccine for Mice. In April 2023, the USDA conditionally licensed a NIAID-supported oral bait Lyme vaccine for mice designed to interrupt the transmission cycle of Borrelia burgdorferi.
• New STI Awards. DMID made five grant awards under a FY 2023 notice of funding opportunity titled, “Understanding the Clinical History of Bacterial Sexually Transmitted Infections (STI) to Accelerate Diagnostic and Vaccine Development” to support studies on the clinical history of syphilis, gonorrhea, and chlamydia.
• Highly Pathogenic Avian Influenza (HPAI) Surveillance Studies. Investigators supported by the NIAID-funded Centers for Research in Emerging Infectious Diseases (CREID) Network and CEIRR program have published findings from surveillance studies designed to characterize the viruses that appear to be killing marine mammals along the coast of Peru. Scientists found that the HPAI viruses were rapidly accruing mutations, including mutations of concern, highlighting an urgent need for active local surveillance to manage outbreaks and limit spillover.
• Recently Published Request for Information. The Office of Science and Technology Policy recently published a Request for Information that invites comments on potential changes to the Policies for Oversight of Life Sciences Dual Use Research of Concern (DURC) and the Potential Pandemic Pathogen Care and Oversight (P3CO) Policy Framework. These policies establish frameworks for review and oversight requirements for certain categories of life sciences research, namely research with certain pathogens and toxins, including at institutions that accept Federal funding for such research.

Presentation: Accessing DMID Preclinical Services – Judy Hewitt, Ph.D., Deputy Director, Office of Biodefense, Research Resources, and Translational Research: Dr. Hewitt provided an overview of DMID’s suite of preclinical services that are available to qualified external requesters to address product development gaps. She described the various programs, which span a biorepository that provides standardized strains and reagents and services that advance various stages of preclinical development for vaccines, therapeutics, and diagnostics. Dr. Hewitt noted that these programs were developed initially to address biodefense research needs but are now focused on all of the pathogens under DMID’s purview. In recent years, these services have been utilized whenever there’s an outbreak, which has allowed DMID to quickly evaluate possible interventions.

Dr. Hewitt outlined the benefits these services provide. For example, they lower the risk for developers to develop products that can be used to reduce the burden of infectious diseases; provide expertise and product development capability; and help move promising discoveries along the product development pathway. They are conducted under agreements that ensure confidentiality and the protection of the product developer’s intellectual property. She discussed the eligibility criteria that are used to consider requests and indicated that the services may be accessed by qualified investigators in academia, industry, and nonprofit organizations, both domestically and abroad. She also noted that there is no requirement to have NIH funding in order to access these services.

Dr. Hewitt described the Indefinite Delivery/Indefinite Quantity contract mechanism used to fund the contractors who are providing these services. She discussed the simplified request process to access these services, which is available year-round, and outlined the roles and responsibilities of DMID staff throughout the process, particularly at the early stage when staff are considering the viability of a request, which requires extensive assessment of several factors such as adequacy of preliminary data. Once a decision is made to support a specific request, a DMID team of SMEs is assembled to finalize the work request plan and execute required agreements. DMID receives feedback on the data generated under the study and a final report is shared with the requester, which becomes their property to use as they see fit.

In closing, Dr. Hewitt noted that detailed information about these programs is available on the NIAID website and that staff are often presenting about these preclinical services at conferences and workshops to publicize their availability.

FY 2025 DMID Concepts Presented for Clearance

The following concepts were presented to the Subcommittee:

Centers of Excellence for Translational Research CETR – This concept aims to support translational research activities to expand the pipeline of medical countermeasures against bacteria or fungi with known and emerging resistance as identified in the Center for Disease Control and Preventions report "Antibiotic Resistance Threats In the United States, 2019.” The DMID Subcommittee recognized the importance of antimicrobial resistance as a growing global public health threat. They agreed there is a need for translational research focused on transforming basic science outcomes (e.g., knowledge, technologies, infrastructure) into new and innovative approaches for prevention, diagnosis, and treatment. The Subcommittee noted that new diagnostics, therapeutics, and vaccines are particularly needed to combat known and emerging resistant bacterial and fungal pathogens. Two Subcommittee members noted the focus on countermeasures against antimicrobial resistant (AMR) bacteria and fungi elevated to urgent and serious threat risks by the CDC is timely and needs to be re-emphasized post-pandemic. One Subcommittee member inquired as to whether Vibrio vulnificus would be included, due to recent infections. Program responded that emergent Vibrio species are not currently part of the concept but would be included if they are added to the CDC list. Ad Hoc Subcommittee member, Dr. Dan Jernigan, offered to connect program officials with the CDC staff in the Division of Foodborne, Waterborne, and Environmental Diseases to discuss this issue. The Subcommittee approved the concept with a unanimous vote.

Evaluation and Testing Services for Vaccines and Other Biologics for Infectious Diseases – This concept would renew a preclinical services program that provides preclinical, nonclinical, and clinical assay services for vaccines and other biologic products. The DMID Subcommittee recognized the significant value to the extramural community in continuing to provide Evaluation and Testing Services for Vaccines and Other Biologics as a part of NIAID's suite of preclinical service contracts that may be accessed by investigators in academia, industry, and nonprofit organizations, among others. Whereas the previous Evaluation and Testing Services for Vaccines and Other Biologics were established with a single contractor, the renewal will use a multi-award IDIQ mechanism to create a pool of available contractors that can compete to perform the requested service. Not only will this competition drive down costs and enable small businesses to participate, but a pool of contractors will increase the breadth of capabilities and new technologies available while decreasing the need to rely on subcontractors. Program assured the Subcommittee that only the best-in-class contractors would be selected for the pool. To address questions from the Subcommittee, program provided a brief overview on how requests from the external research community to use these services are evaluated based on scientific merit and programmatic priorities. The Subcommittee approved the concept with a unanimous vote.

Vaccine (and Other Biologic) Manufacturing Services for Infectious Diseases – This concept would renew a preclinical services program that provides product development and manufacturing support of novel candidates from the proof-of-concept stage through Phase I/II clinical studies. The DMID Subcommittee recognized the value to the extramural community in continuing to support and provide the Vaccine (and Other Biologics) Manufacturing and Characterization Services. During the presentation, program staff described a proposed plan to restructure the program to include four independent task areas. The goal is to “right size” contractor pools to perform specific activities, which should help support the wide scope of supported activities while increasing competition. Program reiterated that offerors could choose to respond to a single task area or to multiple task areas, and also clarified that product innovators may be supported by activities that involve more than one task area. Program also described failed or terminated projects, for example, those that were rejected due to the need for further R&D or that failed due to technical issues that arose during manufacturing. One Subcommittee member commented that it was good to see how not all “failed” projects end candidate development. Another Subcommittee member asked which type of external requestor (e.g., academic, industry, USG) tended to represent the majority of requests. Program staff replied that it differs by preclinical service but that the Vaccine (and Other Biologics) Manufacturing Characterization Services primarily supports small biotech companies or academic investigators since larger institutions do not routinely outsource manufacturing activities with the single exception of the manufacturing of master banks. The Subcommittee approved the concept with a unanimous vote.

Interventional Agents Chemistry Services (IACS) and Interventional Agents Safety and Pharmacokinetic Services (IASPS) – These companion concepts would renew services currently offered under another preclinical services program, the Nonclinical Services for Development of Interventional Agents for Infectious Diseases. The IACS would provide medicinal chemistry synthesis, process optimization, preparation of toxicology batches, formulation development, GMP manufacturing of drug substance and drug product, and release and stability testing. The IASPS would provide product development planning, in vitro Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET), in vivo pharmacokinetics, safety, and toxicology. The DMID Subcommittee was very supportive of the concepts, which will provide a diverse suite of services to support therapeutics product development from early lead optimization through investigational new drug application (IND) enabling studies. The Subcommittee recognized the importance of preclinical services support for advancing the efforts of the science community to develop new therapeutics targeting NIAID priority pathogens. The Subcommittee also acknowledged the many accomplishments of the previous iterations of these services. Finally, the DMID Subcommittee agreed with the rationale for splitting the program into the IACS and IASPS, noting it was a logical decision that will increase competition and diversity of services offered. The Subcommittee approved the concept with a unanimous vote.

FY 2025 ODSET Concept Presented for Clearance

Center of Excellence for Systems Modeling of Infection and Immunity Across Biological Scales – Dr. Reed Shabman, Deputy Director of the NIAID Office of Data Science and Emerging Technologies, presented an FY 2025 concept to the Subcommittee for clearance titled Center of Excellence for Systems Modeling of Infection and Immunity across Biological Scales, which aims to advance modeling research and coordination across all NIAID extramural divisions. The Subcommittee voiced strong support for the concept; it was approved with a unanimous vote.

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

Director’s Report

Carl Dieffenbach, Ph.D., Director, Division of AIDS (DAIDS)

Dr. Dieffenbach’s presentation began with mention of the deeply sad news of the recent passing of ARAC member Dr. Stephaun Elite Wallace and took a few moments to honor his legacy. Dr. Wallace was a research epidemiologist and public health/social justice leader, recognized for his lifelong work was on health disparities of HIV among many of his accomplishments. The COVID-19 epidemic saw him utilize his skills in this arena to lead the CoVPN’s efforts in overcoming health disparities for COVID vaccination. He will be sorely missed.

Mr. Louis Shackelford from the Fred Hutchinson Cancer Center was welcomed to the ARAC. He is the Acting External Relations Director for the HIV Vaccine Trials Network (HVTN) and COVID-19 Prevention Network (CoVPN), leading the engagement efforts with external partners and public health communications for the HVTN and CoVPN. Mr. Shackelford’s work includes guiding HVTN/CoVPN stakeholder engagements and strategies, spearheading community partnerships, crafting external study communications and developing research awareness and educational initiatives for domestic and global HIV/COVID vaccine trials.

In NIAID personnel news, Dr. Dieffenbach noted that Jeanne Marrazzo, M.D., has been selected as NIAID Director and will be joining the Institute in 2 weeks. Dr. Marrazzo is no stranger to HIV research; she has been a fixture in our communities for a very long time and it is going to be a real pleasure to have her on board.

Within DAIDS, Dr. Dieffenbach noted that Mary Marovich, M.D., retired in August after 12 years leading the DAIDS Vaccine Research Program (VRP). Over her tenure, she was responsible for overseeing so many of the large HIV vaccine trials, including the AMP studies. Furthermore, she helped drive the COVID vaccine program and was essential in helping to get all of those activities stood up and push the trials forward. She also led much of the monoclonal antibody work. Jim Lane, Ph.D., is currently serving as the Acting Director of the DAIDS VRP. He is experienced in clinical immunology with extensive lab experience. NIAID will be mounting a global search for a new VRP Director, and we encourage strong candidates to apply. Also, on the DAIDS front, we welcome Catherine Yen, M.D., to the role of Branch Chief of the Protection of Participants, Evaluation and Policy Branch in the Office for Policy in Clinical Research Operations (OPCRO).

Budget Update

For FY 2024, even at the best scenario, the budget will be flat at level funding with the FY 2023 budget - $6.6 billion. A slide for all of NIH displayed the House and the Senate marks; the House mark represents a 22.9 percent cut for NIAID and the Senate mark is level funding. We await discussions about a continuing resolution, or ultimately passing a budget for FY 2024. The best bets are that the Senate will help us to guide to a level clean continuing resolution. We’ll be starting the year conservatively with an established R01 payline at the 8^th percentile with those who quality as new PIs at the 12^th percentile. We will see what happens when we get a formal budget for the year, and we'll make any adjustments based on the dollars available to the payline once a formal budget is adopted for FY 2024.

Scientific Updates

U.S. Preventive Services Task Force Gives Long-Acting PrEP to Prevent HIV an A Grade. The final action from the U.S. Preventive Services Task Force has been published, making long-acting PrEP and oral PrEP available or recommended as a Grade A under the way the legislation has been written. These should all be available through insurance free of charge; however, as many of you are aware, there is movement from the Fifth Circuit to strip these out of the legislation but for now if there is no change and we should be able to get to a good place and have these available. It will be good to have additional choices that have a Grade A allowed for people at risk of acquiring HIV.

Findings from the ACTIV-2/AIDS Clinical Trials Group A5401 Adaptive Platform Trial of Investigational Therapies for Mild-to-Moderate COVID-19. On September 1, the findings from the ACTIV-2 AIDS Clinical Trials Group A5401 Adaptive Platform Trial were published in a supplement to the JID. Eight manuscripts have been published. This is a tour de force going into really good detail about ACTIV-2 and the clinical trial. Congratulations to the ACTIV-2 Team, both from within the division at the ACTG and all of our sites. Congratulations were extended to everyone involved. Dr. Dieffenbach encourages all to look at the findings because we're not done with therapeutics for COVID by any means.

FY 2024 Concepts for Approval by ARAC

Notice of Special Interest (NOSI)—Ending the HIV Epidemic (EHE)

The objective of this new NOSI will be to solicit applications proposing research that is grounded in implementation science and can address the goals of the Ending the HIV Epidemic in the U.S. (EHE) initiative. Projects will leverage established research-community collaborations and scientific advances in HIV prevention, diagnosis, treatment, and outbreak response to advance the EHE goals, using innovative approaches to tailor strategies for the multi-level barriers and strengths in communities disproportionately impacted by HIV. Goals include expanding engagement to better reach communities disproportionately impacted by HIV, and to deliver integrated HIV prevention, treatment, and care services. Grants will be supported by EHE-appropriated funds.

Competing Revisions of Existing NIH Centers for AIDS Research (CFAR) and Developmental Centers for AIDS Research (D-CFAR) Grants (P30)

The objective of this new P30 PAR is to solicit revision applications to expand the role of the CFAR and D-CFAR Developmental Cores to include additional support and infrastructure to diversify approaches, investigators, and research into HIV-related health disparities. This opportunity for revisions allows CFARs and D-CFARs to initiate or expand current efforts to conduct outreach and support research experiences of early-career investigators, including those in high school, undergraduates, post-baccalaureates, graduate students, and post-doctoral fellows, as well as new and new-to-HIV investigators. The NIH CFAR programs support a broad range of research topics. Examples of existing administrative supplements that could be supported by this Revision PAR: Adelante, CDEIPI, and AFRICURE programs.

Comment: The CDEIPI is really a great program and I’ll share a success story. Our UNC-CFAR has one of the CDEIPI; a student from NC Central was accepted to one of the NIH summer training programs and she's planning to go to grad school.

Question: Please clarify regarding no more administrative supplements.

Answer: We won't have the recurring supplements for programs such as Adelante, CDEIPI, and AFRICURE. We're going to reserve the supplements for the types of things supplements were originally intended to achieve. For example, if your freezer breaks, we'll still be able to help you.

Question/Comment: Worldwide there is concern about access to long-acting injectable cabotegravir (CAB-LA) as pre-exposure prophylaxis (PrEP) for HIV. We conduct research to create these choices and create opportunities for people to have the best resources available that they need to protect themselves. I recognize this is outside of our direct purview, but because we have delivered this result and it took so much effort can we please address some of the barriers that we are experiencing worldwide for people to have access to the choices in terms of the problems and challenges with purchase agreements, drug pricing, and other negotiations? What more can be done, if anything, and can we communicate these concerns to the leadership as it's transitioning.

Answer: We believe that leadership up and down the chain is very aware of the concerns and the issues that we're facing. I think the first biggest challenge is getting enough of the product manufactured so that it is available, obtain in-country approval, and then work with partners, such as PEPFAR, Clinton Health Access Initiative, and other groups that really have done a superb job on controlling pricing for antiretrovirals. NIH has the ability to be part of conversations and will continue to advocate.

NIH Office of AIDS Research (OAR): Pharmacy-Centered HIV Research Meeting Report Out - Paul Gaist, Ph.D., and Walid El-Nahal, M.D. (OAR); Michael Stirratt, Ph.D. (NIMH Division of AIDS Research)

The presentation provided a summary, highlights, and the key takeaways of the meeting, Pharmacy-Centered HIV Research: Current Landscape and Future Frontiers, that took place June 28 and 29, 2023.

Panels of the meeting included: meeting community interests across the spectrum of pharmacies – from independent to chain; pharmacist and pharmacy-based approaches for: HIV testing, HIV PrEP, HIV treatment, and HIV syndemic factors and co-morbidities.

Outline of Highlights from the Meeting

• Potential of Pharmacies to Provide HIV Services
• The Existing Momentum for Pharmacy-based HIV Services
• The Current Research Landscape
• Barriers to HIV Services in Pharmacies
• The Need for Future Research
• Opportunities Moving Forward

Next steps include planning group to advance the overall NIH HIV & Pharmacy initiative; information dissemination; publications and/or journal supplement dedicated to this topic; NIH-supported HIV & Pharmacy related efforts (e.g., EHE supplements); and potential future funding announcements.

FY 2025 Concepts Presented for ARAC Approval

Strategies for Eliminating HIV Proteins – Gerard Lacourciere, Ph.D.

Objective: The objective of this proposed new grant NOFO is to support the development of novel therapeutics directed to intracellular HIV targets. During the HIV life cycle, multiple virus-associated proteins are expressed in the infected cell. All are critical to one or another phase of assembly, maturation, or release of the virus. Considering that each protein has a defined role in the life cycle, targeting one or more for elimination may be an effective strategy to obtain a sustained viral remission or cure.

Description: This initiative introduces a new drug discovery paradigm for HIV: controlling virus replication by eliminating viral proteins. The most direct strategy is to eliminate one or more virus-associated proteins from the cell by targeting HIV RNA transcripts with small molecules. Small molecules could inhibit RNA splicing, block translation, or enable the degradation of RNA encoding selected viral proteins. Alternatively, viral proteins can be selectively targeted for degradation by harnessing one of several known cellular processes. These strategies may overcome the limitations of small molecule inhibitors of HIV enzymes by expanding the number of potential targets within an infected cell.

This funding opportunity will support single-project basic research grants that develop novel therapeutics directed to intracellular HIV targets by various mechanisms including but not limited to protein degradation, targeting of viral RNA through inhibiting RNA processing (splicing, translation, etc.) as well as degradation. This initiative will not support the development of small molecule inhibitors of HIV enzyme activity and molecules that enhance latency reversal, or animal studies using nonhuman primates.

Question: This is really novel in terms of therapeutic targets. You had mentioned at the beginning this question of pharmaceutical companies interacting with this; would this be something you envision a group in academia doing with a pharmaceutical company, and, if so, could you specify in the NOFO?

Answer: We will consider that. Thank you.

Comment: I'll just make the point to reiterate that I think this is a really promising approach and very important complement in filling a gap in the current portfolio. This is an area that really should be researched.

Answer: Thank you.

Limited Interaction Targeted Epidemiology: Epidemiology of transmission and treatment of HIV among vulnerable populations in Latin America (LITE-LA) – Gerald Sharp, DrPH

Objective: The main objective of this proposed new grant NOFO is to support large, electronically generated cohorts in Latin America of men who have sex with men (MSM) and transgender women (TGW) who are HIV-negative and follow them to study the epidemiology of HIV incidence. Continued follow-up of those persons who become HIV-positive should be conducted to study the epidemiology of viral suppression. Comparisons of participants by seroconversion status will provide information on geographic and socially defined areas of high HIV incidence as well as on both personal and structural vulnerabilities to HIV infection. Among participants who seroconvert, comparisons of those becoming rapidly engaged in care and who reach non-detectable HIV levels to those whose virus remains detectable will inform on the treatment of HIV in Latin American countries. The NOFO will allow digital trials to determine optimal study approaches, or to pilot evidence-based digital (mHealth and online) HIV prevention and treatment interventions to both reduce HIV incidence and improve treatment in the most vulnerable populations.

Description: Increasing knowledge about HIV epidemics in Latin America is crucial to addressing these epidemics. Smart phones, the internet, and other technologies have changed the ways that MSM and TGW meet and interact and offer new approaches to track and gather information from these populations. Gay dating apps were successfully used in U.S.-based LITE studies to enroll large cohorts of HIV-negatives highly vulnerable to infection. Epidemiology studies that use these and other remote technologies have been able to identify “hot spots” of HIV infection and subgroups of the most vulnerable MSM and TGW who can be prioritized for HIV prevention programs.

These same remote methods, including gay dating apps, are also feasible in Latin America and would be likely to generate important HIV research findings relevant to improving prevention and treatment programs there. Information from proposed studies on risk factors for HIV among Latin Americans may also be relevant to HIV prevention and treatment among persons of Latin American origin living in the United States, a major risk group for HIV.

This initiative will require involvement of an investigator currently residing in each country where research is conducted. Investigators from the United States may be included, but this is not required. The involvement of in-country investigators and the likely involvement of Latin American investigators living in the United States would support the diversity of investigators funded by NIH.

Projects must establish large, electronically accessioned cohorts (with adequate statistical power for conducting epidemiologic research (minimum 5,000 participants) during the first 2 years of funding.

This funding opportunity uses a two-phase grant mechanism (UG3/UH3). The Phase 1 UG3 plan must specify Go/No Go Criteria with the number of participants to be enrolled, anticipated retention level, and number of HIV seroconversions expected in the initial 2-year period. These criteria will be subject to negotiation prior to award. Evaluation of criteria for enrollment and seroconversion will determine eligibility for transition to Phase 2 UH3 awards. If criteria are met, recipients may receive an additional 3 years of support to conduct epidemiological research. Non-investigational new drug behavioral interventions and trials may be included during Phase 2 but are not required.

Comment: This is a really great initiative. I have a doctoral student at UNC who's in a previous LITE cohort and looking at state level discriminatory policies and how it's impacted PrEP uptake. With the rise of discriminatory policies and with the political climate globally now, I think it's a really important platform to measure and track how that's impacting prevention and access to care.

Answer: I agree; there's an advantage in the fact that there's no limits for geography at all because everything's done remotely.

Question/Comment: This is great, and the other LITE initiatives in the United States have been so successful, but my question was that it's almost like you're combining the early LITE and LITE-Viral Suppression. So, this will be across the entire spectrum, either negative or people living with HIV? It seems like this could be hard because you have to link them differently.

Answer: It's a pretty powerful design and we felt that the problem in Latin America is not just prevention, it really is treatment as well, and we need to address both.

Comment: I think the level of representation in this study is amazing and I really appreciate you bringing this to the table.

Answer: Thank you and we appreciate your supportive comments.

Question: Have you considered migrant populations in Latin America?

Answer: It's up to the investigators, but absolutely. Most migrants have mobile phones for participation.

Gender-Affirming Hormone Therapy, Resilience, Immunology, Pharmacokinetics (GRIP) – Kristen Porter, Ph.D.

Objective: The objective of this proposed new grant NOFO is to support critical research needed to inform strategies to prevent and treat HIV and other sexually transmitted infections (STIs) in transgender people. There are many medical and surgical interventions that transgender people undergo as part of gender affirmation that might impact the acquisition and treatment of HIV or other STIs. Despite a growing body of data indicating that gender-affirming hormone therapy (GAHT) may impact the effectiveness of biomedical HIV prevention or treatment strategies, few studies have addressed these issues in this population. For many transgender people, resilience may include the act of affirming one’s gender in a society in which they face significant stigma and many social systemic challenges. Understanding their needs and specifically tailoring programs to transgender people is critical for strengthening resilience and for more effectively addressing comprehensive HIV and other STI prevention in this population.

Description: This initiative will support the following research topics:

• The impact of GAHT on biomedical regimens used for HIV prevention or treatment and/or co-infections with other STIs.
• Studies of pharmacokinetics/pharmacodynamics, including metabolism, and drug-drug interactions between GAHT and antiretrovirals (ARV’s).
• Development of new models (in vitro, ex vivo, in vivo, and in silico) to study the impact of GAHT on the immunology, pharmacology, and safety/efficacy of HIV prevention and treatment regimens and/or co-infections with other STIs.
• The impact of feminization and masculinization regimens on the gastrointestinal (GI) and urogenital mucosa and their role in HIV and STI susceptibility, infection, and acquisition.
• Hypothesis-driven “Omic” studies (e.g., metabolomic, proteomic, transcriptomic, microbiome) and the use of systems biology tools to characterize the impact of the feminizing and masculinizing hormones on HIV susceptibility, including in the GI and urogenital tracts.
• Studies on the determination of active levels of GAHT to address potential variations related to diverse sources of external hormones and various physiological as well as pathophysiological conditions.

Clinical trials will NOT be allowed for this initiative.

Question: I have a question about using the word “resilience” in addition to immunology and pharmacokinetics and outcomes.

Answer: That was a word that was chosen by our partners. Data generated from these types of studies about gender-affirming hormone and antiretroviral interactions might alleviate concerns that antiretrovirals reduce the effectiveness of their hormone therapy which could result in increased uptake, “resilience” of PrEP and overall antiretroviral acceptance.

Comment: It would be great for NIH to sponsor some kind of workshop on this research area at some point. I think what could be learned across different populations would be important.

Answer: We have a workshop in the works.

Long-Acting Drug Delivery Systems for ART Optimization in Children Living with HIV-1 II (LADDS II) – Patrick Jean-Philippe, M.D.

Objective: The objective of this proposed new grant NOFO is to accelerate developments of safe and effective long-acting drug delivery systems for improved, simplified treatment of HIV-1 in children. This NOFO will invite applicants engaged in the development of existing platforms at early product development stages to perform specific preclinical activities that enable product optimization and accelerated translation to children living with HIV.

Description: This initiative will support development of long-acting drug delivery for optimized treatment of HIV-1 in children by stimulating the optimization and evaluation of LADDS formulations in suitable preclinical animal models, at earlier stage of adult development. The formulations should already be developed for non-pediatric and/or non-HIV applications, ideally as part of an adult development program, to increase future market prospects of any product developed as part of this program.

The applications will need to propose a two-phased plan with timelines and milestones for each phase.

• A long-acting platform being developed for non-pediatric or non-ART use.
• A single platform that can deliver a complete ART regimen for HIV treatment.
• LADDS with a minimum dosing interval of 8 weeks.
• Innovative PB-PK modelling approaches to inform optimal LADDS formulation for pediatric use and dose selection to be taken forward in future clinical studies.
• An animal antiviral efficacy study of the LADDS candidate in the R33 phase in age/maturation-matched nonhuman primates.
• Early assessment of preferred user characteristics in the end user population.
• Collaborative research partnerships with industry are required.

The criteria for nonresponsive applications to LADDS II will be:

• de novo LADDS engineering/small molecule discovery work.
• cGMP manufacture activities.
• LADDS not meeting the minimum duration of action defined in the NOFO.
• Use of any live biotherapeutic or vector system.
• Development of broadly neutralizing antibodies.
• LADDS/ARV combinations previously developed for pediatric populations.
• Applications without an industry partner.

Question: It strikes me that this is a concept in which community feedback is really important and so I appreciate the behavioral science user acceptability, but I'm concerned that may come in a little bit late in the process when important decisions have been made. Is it possible to encourage that to happen early before the study gets too far along to change anything?

Answer: Yes, we agree this should be early in the R61 phase. Clear language in the NOFO should highlight and expand on how those activities need to be started early. We hope that we are sending a clear message in terms of what our expectation is and that hopefully that's what will be delivered to us.

Comment: I might encourage you to consider being a little bit prescriptive in this case; hopefully that's not optional.

Answer: We will go back and look at this and see if we can improve with that in mind.

Engineering Durable HIV Vaccine Responses (ENDURE) – Amy Palin, Ph.D.

Objectives: Waning vaccine efficacy against SARS-CoV-2 and consequent boosting have highlighted the importance of durable vaccine responses. How vaccines induce durable responses remains unclear, and there is no consensus on the definition of durable protection. As vaccine candidates for HIV improve, understanding vaccine durability will become more critical, particularly given the booster-weary population. By integrating bioengineering and immunology, this funding concept addresses several objectives: 1) identification of signatures and markers of durable vaccine responses, 2) identification of early immune signals for programming durable vaccine responses, and 3) application of this knowledge to development of more durable vaccines. Predictors or biomarkers of durable responses can expedite clinical trials and vaccine development by establishing immunologic endpoints for regulatory decisions. Such endpoints can accelerate approval of an efficacious vaccine for expansion to a new population or approval of a refined version of an existing vaccine.

Description: This proposed new grant NOFO will support multi-disciplinary R01 research, inclusive of studies of human immunology and appropriate animal models. Clinical trials will not be allowed. Use of samples from trials funded through other mechanisms will be allowed. Applications must propose hypothesis-driven studies of candidate vaccines for HIV. Areas of interest include:

• Defining durable vaccine responses
  • Identification of molecular signatures, biomarkers, and/or predictors of durable responses.
  • Studies of the immunology of durable responses.
  • Investigation of acute innate and adaptive immune responses that program durable vaccine responses.
  • Comparison of platforms, delivery methods, routes of administration, doses, schedules, and other parameters to identify requirements for durable response.
• Measuring durable vaccine responses
  • Development of assays and techniques to measure durable responses (e.g., sampling methods for bone marrow or mucosal tissues, sample processing methods, analytic tools and methods).
  • Identification and application of molecular signatures, biomarkers, and/or predictors of durable responses.
• Engineering durable vaccine responses
  • Engineering and optimization of antigen display, presentation, and other vaccine parameters.
  • Induction of long-lived germinal center, plasma cell responses, and/or other memory responses.

The scope will not include applications focusing on vaccines for pathogens other than HIV, strategies focused on immunogen development or optimization, strategies primarily focused on increasing breadth, strategies employing host cell engineering, or antibody engineering and passive immunization.

Question: There is the need for the external communities to better understand bench science when it comes to vaccines. Folks are a little bit confused at how we got a COVID-19 vaccine so quickly, yet we're still working on development of an HIV vaccine. Has there been any thought given to how to communicate this type of science to communities? With COVID-19 we got a vaccine really quickly and folks weren't prepared to understand the science of why that happened so quickly.

Answer: Absolutely, we can all do a better job of communicating the science. I am not up on strategies for communicating and strive to do a better job of that. The HVTN does a fantastic job with communications.

Strategies for Controlled Release of HIV Vaccine (SCORE-H) – Angela Malaspina, Ph.D.

Objectives: This proposed new grant NOFO aims to advance controlled-vaccine release strategies to improve immune responses for HIV prevention, treatment, and cure and develop simplified or single-shot vaccination strategies. Although HIV vaccine antigens and adjuvants still require optimization and selection, advancing safe, effective, and well-tolerated solutions for the controlled release of vaccines is an unmet need that may improve vaccine effectiveness and practicality, leading to better adherence to complex regimens, fewer adverse reactions, and cost savings.

Description: This initiative plans to capitalize on advances in materials science, novel release technologies, and delivery systems that may provide new solutions to enhance vaccine response quality, potency, and durability by controlled and customized delivery.

Most conventional subunit vaccines are delivered in bolus, which exposes the immune system to antigens for hours or days before being cleared and often necessitates booster shots to increase immunogenicity. Conversely, natural infections expose the body to inflammation and antigens over days to weeks, often resulting in potent and long-lasting protective immunity. The advantage of materials-based platforms is that they can be engineered to improve the stability and loading of multiple vaccine components and their spatiotemporal release, for example, by controlling the time frame and dose of vaccine delivery over weeks or months. Recent studies have shown that a slow-release vaccine is superior to bolus administration at inducing breadth, potency, and durability of antibody responses to HIV antigens by prolonging antigen exposure in the germinal centers, further enhancing the maturation of B cells for strong humoral immune responses. These findings provide a better understanding of the immunological mechanisms after vaccination and raise critical questions about translating preclinical concepts into clinical applications. Further research is crucial in determining how the targeted delivery and duration of exposure to vaccine components impact the interaction with the immune cells, including how to calibrate vaccine release for improved responses while avoiding exhaustion and over-activation. Therefore, given the recent advances in bioengineering and immunology, it is timely to investigate delivery approaches for controlled HIV vaccine release to develop protective and durable broadly neutralizing responses and antiviral T-cell/innate responses while the field is still working on improving immunogens.

This NOFO proposes a biphasic R61/R33 award mechanism with well-defined, negotiated milestones to determine the transition to the second phase.

Specific areas of research interest include, but are not limited to:

• Evaluate controlled-release vaccine platforms optimized for release kinetics, routes of administration, doses, dosing schedules, and delivery to specific cell types and tissues for improved immune responses.
• Investigate longitudinally the advantages of the delivery platform(s) against a robust benchmark, as well as their potential detrimental effects.
• Harness the progress towards controlled-release technologies and thermally stable formulations to develop simplified or single-shot vaccination strategies that mimic multidose regimens, natural infection, or replicating viral vectors.
• Assess the maintenance of the vaccine structure and bioactivity throughout the delivery period, feasibility for GMP manufacturing, safety, and user acceptability of the optimized delivery platforms.

Translational partnerships among academia, industry, and government are required.

The addition of a behavioral component is highly encouraged in the R33 phase to begin understanding end-user preferences for the delivery system attributes and using this information to refine development iteratively. The early integration of behavioral science with product and process designs is essential for translating basic science into products with solid uptake and use.

Clinical trials are not allowed. HIV/SIV immunogens must be used. Animal research is required, including the use of HIV, SIV, SHIV, small animal models, and nonhuman primates.

Question: You indicated that the behavioral component was going to be optional, and I agree with the reviewers that support the behavioral component, but I would certainly suggest that it be a mandatory component. We need to know more about the experience of the user in these studies to inform the field going forward. If there's any way to make the behavioral component mandatory or part of the study requirements it would be recommended.

Answer: OK. Thank you.

Question: What are the controls for this sort of experiment that groups are proposing? If you've got a slow-release strategy where you've got layer upon layer, how do you control for that? You can't really just have a simple placebo, right, because it's persisting in the system longer? So, what are the controls that groups are proposing?

Answer: If you are thinking about a clinical trial, I don't think we are there yet. This is preclinical research. So, I have to think about it. You can compare maybe to injection and prime boost.

NIAID Office of Global Research: U.S.-Brazil and U.S.-South Africa Collaborative Biomedical Research Programs – Joyelle Dominique, MS, MBA

U.S.-Brazil Collaborative Biomedical Research - Phase 2

This initiative will support U.S. investigators working with Brazilian colleagues in collaborative research projects.

Objectives: To increase U.S. scientists’ access to infectious disease and immunology research opportunities in Brazil and support U.S. scientists’ funding for collaborative research projects; and to foster, expand, and strengthen U.S.-Brazil basic, clinical, and translational research collaboration.

U.S.-South Africa Program for Collaborative Biomedical Research - Phase 3 (Infectious Diseases)

This initiative will support U.S. investigators working with South African colleagues in collaborative research projects focused on infectious disease and immunology research [non-HIV/AIDS].

Objectives: To increase U.S. scientists’ access to infectious disease and immunology research opportunities in South Africa and support U.S. scientists’ funding for collaborative research projects; and to foster, expand, and strengthen U.S.-South Africa basic, clinical, and translational research collaboration.

U.S.-South Africa Program for Collaborative Biomedical Research - Phase 3 (HIV/AIDS and STIs)

This initiative will support U.S. investigators working with South African colleagues in collaborative research projects focused on HIV/AIDS and associated areas of research as well as sexually transmitted infections (STIs).

Objectives: To increase U.S. scientists’ access to HIV/AIDS and related research opportunities in South Africa and support U.S. scientists’ funding for collaborative research projects; and to foster, expand, and strengthen U.S.-South Africa basic, clinical, and translational research collaboration.

Question: These are such great initiatives. My question is on the South Africa one – I did not see malaria on the list. Is the list comprehensive?

Answer: Thank you. In fact, we just had a meeting with our Brazilian counterparts this morning where we shared potential areas for collaboration. There is still opportunity for discussion and refinement of the areas of priority; we are always open to discussing important areas of collaboration and can make sure that those are considered.

Question: I assumed that scientists from these areas that we're collaborating with, Brazil and South Africa, are involved with those lists of research-focused areas in an intentional, meaningful way.

Answer: Absolutely. One of the reasons why these programs take a long time to develop and implement is because there are many levels of negotiations. We're working across NIH as well as with the funding agencies in the different countries that are going through their deliberation processes and their strategies. It takes multiple meetings to come together and make sure that we're all aligned and that there's mutual interest. There is a lot of discussion and a lot of input from all of the stakeholders that are involved.

Question: Are these programs just for Brazil and South Africa?

Answer: The other country that we have partnered with in the NIH bilateral program was China. That one is currently on hold. Other countries might be selected. These are small programs and we have a small amount of funding dedicated to bilateral programs. We try to think strategically about how we engage and who we engage with. We want to make sure that the countries have funding to bring to the table because it's important that they are also investing in their biomedical research capacity. There is a lot of interface that my office does with foreign counterparts in many different countries, but these are the most formal programs that we have thus far.

Question: You noted that the cap on these is $300K a year. These countries can be very expensive to work in. We have advocated for increasing the U.S. R01 to a $500K cap. I worry that reviewers are going to expect R01 level science in these programs and this could be challenging given the funding caps.

Answer: Absolutely. And I will say that we have had discussions with our foreign counterparts to see if it would be worthwhile to have a bigger investment in a smaller number of programs. Those discussions are underway.

Comment: It seems as though you should be congratulated for leveraging all of these different parts of these to get as much funding as you had, albeit modest.

Public Comments: None

Ballot Voting Outcome:

All of the concepts presented today were unanimously approved by the voting members of the AIDS Research Advisory Committee.

VII. Adjournment

The meeting of the Council adjourned at 4:30 p.m., on Monday, September 11, 2023.

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.