The 203rd meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened virtually at 10:30 a.m. on Monday, January 30, 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 11:51 a.m. and from 1:00 p.m. to 4:34 p.m. The meeting was closed to the public from 8:30 a.m. to 10:00 a.m. and from 11:52 a.m. to 12:00 noon for review and consideration of individual grant applications. Notice of the meeting was published in the Federal Register.
|Ex Officio Members Present||
|NIAID Senior Staff Present||
Table of Contents
I. Review of Grant Applications
II. Remarks of the Acting Director, NIAID—Hugh Auchincloss, M.D.
III. Guest Speaker—Renee Wegrzyn, Ph.D., Director, Advanced Research Projects Agency for Health (ARPA-H)
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
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 4,471 research and training applications with primary assignment to NIAID for a requested amount of $1,427,694,680 in first-year direct costs and recommended approval of 2,327 applications with $826,021,958 in first-year direct costs.
Dr. Auchincloss opened the Council session by welcoming visitors to the meeting. He introduced five new Council members: Emily Brown, founder and Chief Executive Officer of Free From Market, a digital health and e-commerce company; Dr. Mary Estes, Cullen Foundation Endowed Chair of Molecular and Human Virology and Distinguished Service Professor in the Department of Molecular Virology and Microbiology and Department of Medicine—Gastroenterology and Hepatology and Infectious Diseases at Baylor College of Medicine; Dr. James Gern, Professor of Pediatrics and Medicine at the University of Wisconsin School of Medicine and Public Health in Madison and Vice Chair for Research in the Department of Pediatrics; Dr. Laurence Morel, Professor and Chair of the Department of Microbiology, Immunology, and Molecular Genetics at the University of Texas Health Center San Antonio; and Dr. Guy Palmer, Regents Professor of Pathology and Infectious Diseases and the Jan and Jack Creighton Endowed Chair at Washington State University (WSU) and Senior Director of Global Health for the WSU System. Dr. Auchincloss also introduced a new ex officio member, Dr. Daniel Jernigan, Acting Director of the National Center for Emerging and Zoonotic Infectious Diseases at CDC.
Consideration of Minutes of Previous Meeting
Council considered the minutes of the September 12, 2022 meeting and concepts that had been presented and approved them as written.
Staff and Organizational Changes
Dr. Auchincloss announced appointments and transitions that have taken place since the last Council meeting.
Dr. Anthony Fauci retired as NIAID Director at the end of December, after 38 years as NIAID Director and 54 years as an NIAID physician scientist. On December 16, NIH held a farewell event for Dr. Fauci at NIH's Wilson Hall in Building 1. A global search is underway for a new Institute Director. Dr. Auchincloss is serving as NIAID Acting Director until a new Director is selected.
Dr. Renee Wegrzyn was appointed by President Biden to serve as the first Director of the Advanced Research Projects Agency for Health (ARPA-H).
In November, Dr. Joni Rutter was named Director of NIH's National Center for Advancing Translational Sciences.
Dr. Nina Schor has been selected as NIH Deputy Director for Intramural Research in NIH's Office of the Director. In this role, Dr. Schor will lead the NIH Intramural Research Program and facilitate coordination and collaboration among the 23 NIH Institutes and Centers that are a part of NIH's research community.
Dr. Roger Glass has stepped down from his positions as Director of the Fogarty International Center (FIC) and NIH Associate Director for International Research. FIC Deputy Director Dr. Peter Kilmarx is serving as FIC Acting Director while a search for a new director is conducted.
At the end of December, Andrea Norris retired from her positions as NIH's Chief Information Officer and Director of the Center for Information Technology.
Dr. Auchincloss then presented staff changes that have taken place at NIAID since the last Council.
Gray Handley retired from his position as NIAID Associate Director for International Research Affairs. Greg Folkers and Laurie Doepel stepped down after more than 25 and 30 years of NIAID service, respectively, in leadership and communications roles under the NIAID Director.
Dr. Matthew Fenton retired after 11 years as the Director of the Division of Extramural Activities (DEA). DEA Deputy Director Dr. Kelly Poe is serving as the Acting DEA Director until a permanent DEA Director is selected.
Also in DEA, George Kennedy was named the new Director of the Office of Acquisitions. He replaces Chuck Grewe who retired after 44 years of federal service.
Dr. Michael Ison is the new Chief of the Respiratory Diseases Branch in the Division of Microbiology and Infectious Diseases (DMID).
In the Division of AIDS (DAIDS), Dr. Andrew Vernon was selected as Chief of the Tuberculosis Clinical Research Branch in the Therapeutics Research Program.
In the Division of Allergy, Immunology, and Transplantation (DAIT), Dr. James McNamara retired as Chief of the Autoimmunity and Mucosal Immunology Branch. Dr. Ellen Goldmuntz is currently serving as Acting Branch Chief.
In the Division of Clinical Research, Mary Smolskis has been named Director of the Office of Planning and Operations Support.
Tributes and Awards
Dr. Auchincloss recognized Dr. Cliff Lane, who received the 2022 Paul A. Volcker Career Achievement Medal given by the Partnership for Public Service, and Alex Rosenthal, who received the Presidential Rank Award for his service as NIAID's Chief Technology Officer.
NIAID won a 2022 U.S. Patent and Trademark Office's Patents for Humanity Award in the COVID-19 category. This prestigious award recognizes our Technology Transfer and Intellectual Property Office and the ingenuity, foresight, dedication, and hard work of NIAID scientist inventors and their collaborators.
Science magazine released its 2022 list of top 10 advances across the sciences. NIAID scientists contributed to two of the runner-up breakthroughs, which included research on respiratory syncytial virus vaccines and Epstein-Barr virus as a potential cause of multiple sclerosis.
Meetings and Events
On December 8, NIH hosted the Ninth Global Health Workshop with the Gates Foundation, which provided an opportunity to discuss progress on joint projects.
Dr. Auchincloss reported on NIAID staff meetings with international delegations, including in-person and virtual meetings with representatives from the United Kingdom, Canada, India, the European Union, Australia, Poland, France, the WHO African Region, Korea, Germany, and Mali.
The President is required to submit his annual budget to Congress by the first Monday in February. Information about the FY 2024 budget should be available in the next few weeks.
An omnibus spending bill for fiscal year (FY) 2023 was passed in December 2022. NIH received an overall increase of 5.5 percent, and NIAID received a 3.8 percent increase.
Dr. Auchincloss summarized NIAID's FY 2023 financial management plan. Our R01 payline is set at the 11 percentile for established principal investigators (PIs) and the 15 percentile for new PIs. NIAID does not plan to make programmatic cuts to noncompeting and competing grants. Competing research initiatives were cut up to 20 percent from their planned budget level. Our estimated success rate for research project grants is 18 to 22 percent.
NIAID's FY 2023 budget includes substantial earmarks for antimicrobial resistance, universal influenza vaccine, and the regional biocontainment laboratories.
Dr. Auchincloss gave a brief update on the funding NIAID received through two emergency supplemental funding packages: the Coronavirus Aids, Relief, and Economic Securities (CARES) Act and the Coronavirus Preparedness and Response Supplemental Appropriations Act. The emergency supplemental funding provided NIAID with $1.5 billion and is available until September 30, 2024. Of these funds, NIAID has provided $1.33 billion in support of extramural and intramural investigators to address the scientific areas that are most critical to understanding COVID-19 and advancing medical countermeasures. The remaining $198 million will be awarded to address the most urgent public health and scientific research needs.
NIAID also received COVID-19 funds from HHS through a variety of other mechanisms. This money has been used to fund clinical trials that led to the approval of vaccines and centers to develop new therapeutics.
On September 14, 2022, Dr. Fauci testified at a Senate Health, Education, Labor, and Pensions Committee hearing on the federal response to Mpox (formerly monkeypox).
On December 1, 2022, the Congressional HIV/AIDS Caucus, along with the Global AIDS Policy Partnership and the Federal AIDS Policy Partnership, held a World AIDS Day event honoring Dr. Fauci for his decades of HIV research and service in the global fight against AIDS.
Dr. Auchincloss thanked NIAID staff who have participated in many Congressional briefings and events on behalf of NIAID.
Dr. Auchincloss outlined Congressional leadership changes following the recent elections. In the Senate, Senator Chuck Schumer remains the Majority Leader, and Senator Mitch McConnell is the Minority Leader. In the House of Representatives, Representative Kevin McCarthy is now Speaker of the House, and Representative Hakeem Jeffries is now House Minority Leader.
Dr. Auchincloss provided Congressional committees and subcommittees leadership updates in the House of Representatives and Senate.
Other Information Items
Dr. Auchincloss began by listing examples of emerging and resurging infectious disease outbreaks inside and outside of the United States in 2022.
He then gave a summary of the past 3 years of COVID-19, presenting information about the number of confirmed cases and hospitalizations, most recent variants, therapeutics available, COVID-19 vaccines available in the United States, hospitalizations by vaccination status, efforts to develop next generation vaccines, and NIAID awards to support pan-coronavirus vaccine development.
Dr. Auchincloss provided global HIV statistics. In 2021, 38.4 million people were living with HIV, and there were 1.5 million new infections and 650,000 deaths. He mentioned the disappointing results of an experimental HIV vaccine regimen, which was found to be safe but ineffective.
He concluded with research updates on a monoclonal antibody for malaria, Ebola, a Marburg vaccine, universal influenza vaccine efforts, non-viral asthma attacks, monoclonal antibodies providing protection against Epstein-Barr virus infection, and predictors of antibody response to vaccination.
III. Guest Speaker—Renee Wegrzyn, Ph.D., Director, Advanced Research Projects Agency for Health (ARPA-H)
Dr. Renee Wegrzyn introduced herself and shared her background in terms of how it relates to infectious diseases. She presented ARPA-H's mission, which is to accelerate better health outcomes for everyone, and President Biden's vision of ARPA-H to pursue ideas that break the mold on how we normally approach fundamental research. ARPA-H is not mandated to work on any one disease, and its customers are the American people.
Dr. Wegrzyn provided an overview of ARPA-H's organization within HHS. ARPA-H will hire program managers who will have a term appointment of 3 years that can be renewed for another 3 years. Program managers will identify a health-related challenge, define the problem, and launch a program to solve the problem.
Dr. Wegrzyn gave details about the ARPA-H Model and Program Lifecycle, which moves the problem from ideas to solutions in the real world. ARPA-H has identified four initial mission focus areas: 1) Health Science Futures—expanding what's technically possible, 2) Scalable Solutions—reaching everyone quickly, 3) Proactive Health—keeping people from being patients, and 4) Resilient Systems—building integrated healthcare systems.
To close her presentation, Dr. Wegrzyn summarized the hiring process for program managers, some recent ARPA-H milestones, and priorities moving forward.
IV. Report of the Allergy, Immunology, and Transplantation Subcommittee–Daniel Rotrosen, M.D., Director, DAIT
Dr. Rotrosen welcomed the subcommittee members to the 203rd meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting.
Dr. Rotrosen presented the following scientific and Division activities:
Staff and Organizational Changes
James McNamara M.D., Ph.D., Dr. McNamara retired as Chief of the Autoimmunity and Mucosal Immunology Branch (AMIB) at the end of 2022. Under his astute leadership, the Autoimmunity Centers of Excellence evolved into a highly interactive collaborative network that is recognized nationally as a major contributor to exploring high priority basic and clinical questions in autoimmunity. He also played a critical role in the success of the Immune Tolerance Network, an international consortium of over 80 investigators dedicated to the clinical evaluation of novel, tolerance-inducing therapies for autoimmune diseases, allergic diseases, and the prevention transplant rejection.
Dr. McNamara began his distinguished career at NIAID in 1995 in DAIDS, first as Chief of the Clinical Development Branch, followed by Chief of the Pediatric Medicine Branch. Nine years later, he joined DAIT as the AMIB Chief and during his tenure as Chief he also served as the Acting Associate Director of the Clinical Research Operation Program from 2007 to 2014. Prior to joining NIAID, Dr. McNamara was an Assistant Professor of Pediatrics at Yale University School of Medicine from 1988 to 1991; a Senior Associate at the Howard Hughes Medical Institute from 1988 to1990; and a post-doctoral fellow at the same institute from 1985 to 1988. Dr. McNamara received his M.D. from the University of Vermont College of Medicine in Burlington, Vermont, followed by a Residency in Pediatrics and a Fellowship in Allergy/Immunology at Yale University School of Medicine, New Haven, Connecticut.
Ellen A. Goldmuntz M.D., Ph.D., Dr. Goldmuntz has been selected as the Acting Chief of the Autoimmunity and Mucosal Immunology Branch. She joined the Division of Allergy, Immunology and Transplantation as a medical officer in 2003 and in 2011 became Chief of the Rheumatologic Diseases Section, within the Autoimmune and Mucosal Immunology Branch. Prior to joining NIAID, Dr. Goldmuntz was an Assistant Professor of Pediatrics in the Division of Rheumatology at Children's National Medical Center in Washington, DC. She completed her residency at Children's National Medical Center followed by a pediatric rheumatology fellowship in a combined program with the Children's National Medical Center and NIH. Dr. Goldmuntz attended Albert Einstein College of Medicine where she received an M.D. and a Ph.D. through the Medical Scientist Training Program. She received her undergraduate degree in Molecular Biophysics and Biochemistry from Yale.
Selected Funding Opportunities
Allergy, Asthma, and Airway Biology Branch
Analytical Challenges in Omics Research on Childhood Asthma and Allergy. On December 6 and 7, 2022, a virtual workshop was held by the NIAID/DAIT/AAABB. The meeting brought together clinicians and researchers with expertise in asthma and allergy, and experts in the various types of omics data. The major objective was to provide guidance to NIAID in defining opportunities for advancing childhood asthma and allergy research, by identifying gaps and solutions for collecting, analyzing, and integrating omics data. Specifically, the workshop participants worked to identify strategies to utilize omics data to advance understanding of the pathways underlying childhood asthma and allergy, including disease susceptibility and tolerance to potential allergens. The workshop co-organizers, presenters and NIAID staff are collaborating on a workshop summary for publication in the near future.
2022 Annual Asthma and Allergic Disease Cooperative Research Center Face to Face Meeting (AADCRC). On November 9 and 10, 2022, NIAID virtually held the 17th annual meeting of the AADCRC investigators. The 2-day meeting of PIs, co-investigators, students, and program staff included presentations from the 11 NIAID-funded research Centers, as well as 4 NIAID-funded Program Project grant teams, and a special session featuring the work of young AADCRC investigators supported by the opportunity fund.
Basic Immunology Branch
Molecular Mechanisms of Combination Adjuvants (MMCA) Annual Meeting. On October 20 and 21, 2022, the annual meeting of the Molecular Mechanisms of Combination Adjuvants program took place in Bethesda, Maryland. During the meeting, the participating investigators presented updates on research performed during the first year 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 on the mechanistic differences between immune responses to adjuvanted vaccines and pathogenic infection. Scientific roadblocks and opportunities for collaboration among investigators were also discussed at the meeting.
Advancing Vaccine Adjuvant Research for Tuberculosis (AVAR-T). On October 24, 2022, the virtual kick-off meeting for the tri-divisional AVAR-T program was held by videoconference. One AVAR-T contract was awarded in FY 2022 to the University of Sydney/Centenary Institute. The goal of the AVAR-T program is to further the development of preventive, including post-exposure, Tuberculosis vaccines through side-by-side comparisons of adjuvants in combination with Mycobacterium tuberculosis (Mtb) immunogens, and to establish immunological profiles of adjuvants that work through different mechanisms. These studies will facilitate the identification of the most promising adjuvant/Mtb immunogen candidates for clinical development and potential immune correlates of protection to provide knowledge for future clinical development. The studies involve procurement of adjuvants and Mtb immunogens, formulation of adjuvant/Mtb immunogen candidates, preclinical safety and immunogenicity studies in small animals, evaluation of lead candidates in non-human primates and non-clinical IND enabling studies.
Immune Mechanisms of Protection Against Mycobacterium tuberculosis Center (IMPAc-TB). On November 16 and 17, 2022, the third annual meeting of the IMPAc-TB contract program was held as a hybrid meeting in person (Rockville, Maryland) and virtual attendance. Each of the principal investigators of the three contracts presented an overview of their programs and the accomplishments achieved and challenges encountered during the past year of the award. The overarching goal of the IMPAc-TB program is to identify and characterize immune responses required to 1) protect a host from initial Mycobacterium tuberculosis (Mtb) infection, 2) establish latent infection, or 3) progress 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.
Impact of Initial Influenza Exposure on Immunity in Infants. On November 17 and 18, 2022, investigators and their teams awarded under this program met via videoconference. Two projects are supported under this program, which is a partnership between the Division of Microbiology and Infectious Diseases and the Division of Allergy, Immunology and Transplantation, NIAID. The awarded groups are led by a) Paul Thomas (St. Jude Children's Hospital) and Aubree Gordon (University of Michigan) and b) Mary Staat (Cincinnati Children's Hospital Medical Center). The goal of this program is to establish, follow, and characterize longitudinal cohorts of infants to determine how initial and repeated natural influenza infections and/or influenza vaccinations shape infant and childhood immunity to future influenza exposures. Investigators presented recent updates and progress in each of their programs. The meeting encouraged investigators to exchange ideas and to further collaborations among the investigators.
Crosstalk between Skin Microbiota and Immune System in Health and Disease Workshop. On December 1 and 2, 2022, a virtual workshop entitled "Crosstalk between Skin Microbiota and Immune System in Health and Disease" was held by NIAID's Division of Allergy, Immunology, and Transplantation in partnership with the Division of Microbiology and Infectious Diseases. The workshop was chaired by Drs. Richard Gallo and Elizabeth Grice and focused on recent advances in understanding the role of skin microbial commensals in shaping host immune system development and regulating host immunity to pathogens, parasites, allergic diseases, and wound healing. Several speakers showcased novel skin microbiome-based therapeutics for infectious and allergic diseases and cancer. The meeting included discussions on knowledge gaps, current challenges, and future research directions that may be pursued to expand understanding of the role of skin microbiota in host immunity and to promote the development of innovative therapeutics that leverage skin microbial commensals to treat pathogenic infections, allergic and inflammatory diseases, and cancer.
Cooperative Centers on Human Immunology (CCHI) Program. On December 8 and 9, 2022, the CCHI annual meeting was held in person, with a virtual option, in Bethesda, Maryland. This program aims to support mechanistic and hypothesis-testing studies to understand human immune responses to pathogenic infections, vaccination, and adjuvants, as well as in immune-mediated diseases. Investigators from the eight centers presented their research progress, including recent updates on the COVID-19 studies supported by supplement awards. Six awardees who received CCHI Infrastructure and Opportunity Fund support in 2022 also presented their work. A virtual poster session was held over the week, allowing trainees to showcase their research. Four of the posters were selected for short talks during the CCHI progress meeting. The CCHI program continues to provide a platform for advancing understanding of human immunity by building collaborations, sharing the best practices, and leveraging resources among the groups.
Emerging Science and Technology in Transplantation (ESTT) Cooperative Group. On October 4, 2022, the steering committee meeting for the recently renewed ESTT program was held virtually. The current ESTT program is focused on applying research advances in areas of targeted delivery, intravital imaging, and the microbiome to transplantation. Each of these three priority areas is represented in the new consortium, which consists of five multidisciplinary projects. During the meeting, consortium investigators presented their projects and future research goals. Topics presented included targeting the lung allograft endothelium; genetic engineering of kidney allografts by delivery of viral vectors during ex vivo organ perfusion; novel lymph node-targeted drug delivery; in vivo imaging of immune regulation; and mechanisms of microbiome-driven outcomes in cardiac transplantation. The meeting was highly interactive with productive discussions and exchange of ideas.
The National Academies of Sciences, Engineering, and Medicine Committee on the State of the Science and Future Needs for Nonhuman Primate Model Systems. On November 21, 2022, the Transplantation Branch participated, as the NIAID representative, in a public meeting of the NIH-Wide Nonhuman Primate (NHP) Resource Planning Working Group. This meeting provided committee members with an overview of 1) the NIH response to recommendations made in the 2018 Office of Research Infrastructure Programs report, Nonhuman Primate Evaluation and Analysis, 2) institute-specific research areas where NHP models are particularly valuable, and 3) ways collaboration between researchers utilizing new approach methodologies and researchers working in NHP models might be further enhanced with the overall goal of both increasing utility of NHP model research while reducing the number of animals required to produce meaningful results.
Immunobiology of Xenotransplantation Cooperative Research Program (IXCRP). On November 29, 2022, IXCRP investigators held a virtual annual steering committee meeting to present and discuss their research progress and consortium business issues. The IXCRP focuses on addressing the immunological and physiological barriers influencing xenograft survival and function in swine-to-nonhuman primate (NHP) models of pancreatic islet, heart, lung, kidney, and liver xenotransplantation. The long-term goal is to expand availability of donor organs and cells by enabling use of swine organs/cells as a bridge or definitive solution to treat end-stage organ failure. The meeting included presentations by IXCRP 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 on availability of genetically modified swine and specific-pathogen free baboons, respectively.
Last year, a team at the University of Maryland Medical Center, led by IXCRP investigator Drs. M. Mohiuddin and B. Griffith, transplanted a 10-gene modified pig heart into a patient for the first time and as a last resort, extending the patient's life for 60 days. This substantial milestone has heralded a new era of xenotransplantation research in the human decedent model, which, in conjunction with new insights from preclinical swine-to-NHP models, promises further advancement toward a future clinical xenotransplantation trial.
Nonhuman Primate Transplantation Tolerance Cooperative Study Group (NHPCSG). On December 14, 2022, the annual NHPCSG Steering Committee Meeting was held virtually. This multi-institute program supports two U01 and four U19 projects focused on evaluating novel and refining existing regimens for the induction and maintenance of transplant tolerance in nonhuman primate (NHP) models with accompanying mechanistic studies designed to elucidate the immunologic basis of tolerance and/or rejection. The meeting included U-award project presentations, updates on short-term projects funded by the Opportunities Pool, and presentations from key partner programs, the NHP Reagent Resource, and the NHP MHC and KIR Allele Discovery and Typing Technology Development contract. The NHPCSG plays a vital role in evaluating novel therapeutic approaches in a highly translational model and has helped transition these approaches and/or inform clinical trials in transplantation, including those testing co-stimulation blockade, mixed chimerism, regulatory dendritic cell infusion, and targeted inflammation reduction to improve transplant outcomes. Two of the principal investigators in the recently recompeted Clinical Trials in Organ Transplantation consortium are current NHPCSG members.
FY 2024 Research Concept Clearances Presented to Division Advisory Council
The subcommittee endorsed and unanimously approved the following four Research Concept Clearances:
- Innovations in Functional B Cell Epitope Discovery: This program supports the discovery of novel B cell epitopes, elucidation of mechanisms of antibody-mediated protective immunity and/or mechanisms of antibody-mediated pathology, and use or expansion of advanced technologies for epitope discovery and validation.
- T Cell Immune Epitope Discovery and Mechanisms of T Cell Protection: The primary purpose of this solicitation is to support highly interactive, multi-disciplinary teams whose research efforts are focused on large-scale discovery of 1) T cell immune epitopes associated with infectious or autoimmune diseases, commensal organisms, or alloantigens influencing transplant outcomes, 2) validation of these epitopes, and 3) defined mechanisms of T cell immune protection or immune-mediated pathogenesis in humans.
- NIAID SPF Macaque Breeding Colonies: This initiative will continue support for the maintenance, care, and breeding of NIAID-owned Indian rhesus macaque (Macca mulatta) and Mauritian cynomolgus macaque (Macca fascicularis) specific pathogen-free (SPF) breeding colonies.
- Immune Mechanisms at the Maternal-Fetal Interface (R01, Clinical Trial Not Allowed): The objective of this initiative is to determine the roles and interactions of immune cells at the maternal-fetal interface and to elucidate the effects and mechanisms by which pathogenic infection, vaccination, or environmental perturbations during pregnancy impact these cells and the developing fetal immune system.
V. Report of the Microbiology and Infectious Diseases Subcommittee–Emily Erbelding, M.D., M.P.H., Director, DMID
Dr. Emily Erbelding, Director of the Division of Microbiology and Infectious Diseases (DMID), chaired the NIAID Microbiology and Infectious Diseases Council Subcommittee meeting on January 30, 2023. Dr. Erbelding welcomed two new members to the DMID Subcommittee, Dr. Mary Estes and Dr. Guy Palmer. She also noted that we have a new Ex Officio member from the Centers for Disease Control and Prevention, Dr. Daniel Jernigan. She provided a DMID personnel update, recognizing new staff appointments made in the Division since the last Council meeting, including: Dr. Michael Ison, Director of the Respiratory Diseases Branch (RDB); Drs. Kate Bradford, Kevin Schully and Michelle Arnold in RDB; Dr. Fayna Diaz San Segundo in the Office of Biodefense, Research, Resources and Translational Research (OBRRTR); Ms. Brenda Dorsey in the Office of Clinical Research Affairs; and Dr. Keehwan Kwon in the Office of Genomics and Advanced Technologies. In addition, she reported on recent retirements, including Dr. Michael Schaefer (OBRRTR), Dr. Chris Beisel (Virology Branch) and Ms. Karen Bateman (Office of Scientific Coordination and Program Operations).
Following staff introductions, Dr. Erbelding provided a report on recent DMID activities of note:
- In response to FY 2022 House appropriations report language, NIAID created a Strategic Plan for Research to Develop a Valley Fever Vaccine. After stakeholder input was considered, the plan was finalized and posted on the NIAID website. The plan describes several strategic priorities to advance research in this area. Related, NIAID released a Notice of Special Interest to advance research towards this important goal.
- Dr. Erbelding provided an update on the OVERCOME study, which aims to determine the utility of colistin for treatment of multi-drug resistant Gram-negative bacterial infections when used alone, or in combination with a carbapenem. This trial demonstrated the feasibility of enrolling in this difficult-to-reach, critically ill population and further showed that the addition of a carbapenem did not improve treatment outcomes and only risked the potential emergence of additional carbapenem resistant infections.
- Dr. Erbelding reported the status of an early-stage Antibacterial Resistance Leadership Group (ARLG) clinical trial evaluating bacteriophage therapy in adults with cystic fibrosis (CF) who carry P. aeruginosa in their lungs. Few novel antibiotic agents recently approved by the FDA have substantial activity against highly drug-resistant P. aeruginosa, which remains the most common pathogen responsible for CF exacerbations. The study opened to enrollment in October 2022.
Finally, Dr. Erbelding presented four topics for inclusion in the 2024 Small Business Innovation Research (SBIR) Contract Solicitation for the Subcommittee's consideration. All were approved by the Subcommittee:
- Development of Bacteriophage for Treatment of Mycobacterial Infections – The objective of this topic is to provide support for preclinical research and development of therapeutic phage products that target mycobacteria.
- Novel Diagnostic Biomarker Discovery and Validation for Malaria and Select Neglected Tropical Diseases (NTDs) – The objective of this topic is to support combined genomic, proteomic, metabolomic, and bioinformatic approaches to identify and characterize novel malaria and/or NTD diagnostic biomarkers (either parasite or host response biomolecules) in human biofluids.
- Alternatives to Benzathine Penicillin for Treatment of Syphilis – The objective of this topic is to support preclinical development of lead candidates for syphilis indications or repurposing of drugs to be more suitable for syphilis treatment.
- Development of a Serological Test for Herpes Simplex Virus Type 1 and 2 (HSV-1 and HSV-2) Infections – The objective of this topic is to develop a serological test for genital herpes that retains high specificity, sensitivity, and positive predictive values; distinguishes between HSV-1 and HSV-2; and uses technology such that the test could be distributed for broad use.
Guest Speaker: Dr. LeShawndra Price, Director, Office of Research Training and Special Programs – Dr. Price provided an overview of NIAID's training portfolio, sharing information about several training recommendations endorsed by NIAID leadership in February 2019. These recommendations are being implemented over a 5-year period and will increase the NIAID extramural training budget. She also described a new NIAID funding opportunity announcement that aims to support research from new and "At-Risk" investigators from diverse backgrounds, including investigators from underrepresented racial and ethnic groups, in order to enhance the diversity of R01-funded investigators. Finally, she noted the availability of NIAID training resources on the NIAID website and summarized several activities that her office will pursue to further enhance NIAID's training portfolio.
FY 2024 Concepts Presented for Clearance
The following concepts were presented to the Subcommittee. All concepts were approved.
Bioinformatics Resource Centers for Infectious Diseases (BRC) – The objective of this concept is to continue support of computational infrastructure and bioinformatic knowledgebases to harmonize and integrate infectious diseases multi-omics research data, advance innovative bioinformatics technologies, and provide cutting-edge informatics services during a public health emergency. Subcommittee members supported the concept and agreed that the current BRC program is productive and has accommodated the research community's evolving needs and rapid changes in the complexity and volume of biomedical data and bioinformatics technologies. The Subcommittee also noted that the program is positioned to implement 'production-level' data processing and input from public repositories and sustainable knowledgebases that advance technology, including machine learning and artificial intelligence, for clinical applications in real-world scenarios. Furthermore, it was noted that the BRCs will continue interacting with other knowledgebases, including those with host response data. One Subcommittee member inquired whether early career investigators were aware of the resources and services provided by the BRC program. NIAID staff responded that the BRCs have robust outreach activities through multiple channels, including sharing information at critical scientific meetings, establishing an open forum for research communities, communicating on numerous social media platforms, and conducting regular webinars and in-person workshops.
Animal Models for Hepatitis B and C – The objective of this concept is to develop and optimize animal models to evaluate efficacy and further development of curative strategies for hepatitis B virus (HBV) or vaccines for hepatitis C virus (HCV). The DMID Subcommittee recognized the pressing need for tractable and convenient animal models for HBV and HCV to facilitate the development of curative strategies for HBV and prophylactic vaccines against HCV. The Subcommittee members acknowledged the daunting challenges and were enthusiastic in their support of this concept, and the notion that even limited models might be useful to target specific aspects of virus-host interaction. Given the widespread existence of hepadnaviruses in nature, a systematic, universal search for a mouse strain that might harbor a related virus was advised.
Collaborative Partnership to Advance Global Health Research – The objective of this proposed limited competition is to develop, establish, implement, and maintain a successful collaborative partnership to advance NIAID priorities, support NIH collaboration on global health, and advance health research internationally. The DMID Subcommittee recognized the need for this important international program. One Subcommittee member noted that this program extends beyond DMID and NIAID and may include involvement of other NIH institutes and centers. In addition, the Subcommittee members noted that the cooperative agreement (U01) appears to be the best mechanism available as it provides for close coordination between NIH and the recipient. It was noted that the base award for the program is modest but provides a level which can be built upon, if necessary, for response to new global health challenges. Another Subcommittee member noted that the program is flexible and provides a format that allows responses to unanticipated opportunities and needs, and that it will be important to have a framework and conceptual guidelines to determine which activities will be supported.
International Research in Infectious Diseases – The objective of this concept is to provide support for meritorious, high-priority, regionally-relevant infectious disease research by international investigators in resource-limited countries. The DMID Subcommittee recognized the importance of continuing the program and expressed overall support, acknowledging the potential of research capacity building in endemic areas and increased access to organisms and diseases of interest to NIAID. DMID Subcommittee members requested additional clarification on the classification as a new concept, since a history of the program was provided. NIAID staff responded that the mechanism to be used going forward is a request for applications, which will allow NIAID to cluster review into a single meeting rather than in disparate review groups. Subcommittee members noted the disproportionate number of awards made to institutions in a select few upper-middle income economy countries and encouraged increased participation from underrepresented countries. NIAID staff responded in agreement, noting that plans are currently underway to encourage applications from institutions in low- and lower-middle income economy countries. Along those lines, one Subcommittee member suggested training in NIH-style grant writing as a means of increasing the participation and success of underrepresented institutions. In addition to trainings that are currently available through NIH at-large, plans are in place to conduct an informational webinar as well as annual seminars as part of the IRID, where such training could also occur. Lastly, one Subcommittee member questioned the ability to target specific pathogens, such as those with outbreak potential (Ebola virus, etc.). It was noted that the concept is designed to be scientifically broad.
Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness Network (ReVAMPP) – The objective of this program is to develop and validate generalizable vaccine strategies for prototype viruses that can be applied to other closely related family members and advance scientific knowledge needed to develop vaccines and monoclonal antibodies (mAbs) for prototype viruses from families with high pandemic potential. Three separate concepts are included under this network, including a concept to establish Centers for Bunyavirales, Paramyxoviridae and Picornoviridae and, separately, Centers for Flaviviridae and Togaviridae. A companion funding opportunity would establish a Network Coordination and Data Sharing Center to assist in the administration and management of information exchange and collaboration among the ReVAMPP Research Centers. The DMID Subcommittee recognized the importance of conducting vaccine and monoclonal antibody research and development using the prototype pathogen approach to better prepare for future virus outbreaks. In response to a Subcommittee member's question about whether PIs may propose research with one virus family, NIAID subject matter experts noted that the intent is for each Center to work on multiple virus families. Program also noted that the Research Centers will comprise teams of investigators, anticipating that groups of investigators will be working together in one center, bringing in individualized expertise. A Subcommittee member asked about the activities and industry partnerships for the different virus families, particularly the Bunyavirus field, which may be more limited. Program responded that the spectrum of activities and integration of industry partnerships will likely differ for the different families. One Subcommittee member asked whether coordinating centers had been successful for other programs. Program responded that they were able to leverage lessons learned from coordinating centers for other programs when developing the concept for the ReVAMPP Coordination Center. One Subcommittee member noted the importance of this research and highlighted that it would generate many important reagents and inquired about how they would be shared with investigators in the field. Program responded that collaboration is a key component of the network and other NIAID programs such as BEI resources will be utilized to facilitate reagent sharing. One Subcommittee member asked if there was potential for overlap with the Vaccine Research Center (VRC). Program responded that this program was complimentary to research being conducted at the VRC and that DMID staff has been regularly coordinating pandemic preparedness efforts with the VRC and other NIAID components.
VI. Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)–Carl Dieffenbach, Ph.D., Director, DAIDS
Welcome and Approval of Minutes
Kenneth A. Freedberg, M.D., M.Sc., (Chair)
Dr. Freedberg welcomed everyone and the ARAC members approved the minutes of the September 12, 2022 meeting. This was Dr. Freedberg's last meeting as Chair of ARAC and Drs. Agarwal, Gupta, and Frank are also ending their term on the ARAC.
Director's Report and SBIR Contract Topics
Carl Dieffenbach, Ph.D.
Dr. Dieffenbach's presentation began with thanking members who will be leaving the ARAC, especially Dr. Freedberg for his leadership as Committee Chair.
Dr. Dieffenbach announced that Andrew Vernon, M.D. has joined DAIDS as Chief of the TB Clinical Research Branch in the Therapeutics Research Program.
Today's ARAC meeting will be somewhat different as it will be focused on lessons learned from SARS-CoV-2 and the COVID pandemic.
It is currently unknown what is in the President's budget for FY 2024 and when it will be released. The 2023 Budget was discussed, and the key point was that NIAID received a 3.8 percent increase (AIDS allocation is not included in this total).
NIAID FY 2023 Interim Financial Management Plan
- R01 Payline: The percentiles increased from the 10th to the 11th percentile. New PIs are at the 15th percentile.
- We generally do not restrict or down negotiate non-competing or competing grants or contracts.
- Certain research initiatives will be cut up to 20 percent, with an estimated success rate between 18 and 22 percent for the entire Institute.
Scientific and Programmatic Updates
Imbokodo Trial (Companion to Mosaico)
- This study was discontinued following the DSMB recommendation.
- Data showed an equal number of infections in both active and placebo arms.
- Study participants have been notified and the findings are moving quickly toward publication and release.
- This global study was in men in Europe, South America, and the United States, and this population had access to PrEP. The challenge going forward is how can these unreachable people be reached and provide them the necessary services to prevent HIV acquisition.
Long Acting Cabotegravir (Apretude)
The U.S. Prevention Services Task Force (USPSTF) gave Apretude, a grade "A". This will now move through their process of getting validated as a grade A, which may lead within a year or two to full coverage of this prevention option under the Affordable Care Act (ACA), ACA-approved health plans. This is a big step forward as when TDF/FTC was approved by the FDA in 2012; the USPSTF took almost 6 years before they gave oral, daily PrEP a grade A.
DAIDS Response to the COVID-19 Pandemic
Today's meeting will focus on clinical activities, and also highlight the significant contributions to the SARS-CoV-2 pandemic by the pre-clinical and clinical research virology laboratories and clinical sites which pivoted to work on COVID.
The Division had a two-pronged attack on SARS-CoV-2:
- To define the basic mechanisms of virology and immunology.
- To play the pivotal roles in developing vaccines, therapeutics, and monoclonal antibodies to prevent and treat SARS-CoV-2.
Dr. Dieffenbach focused his comments on the Division's clinical activities:
- In April 2020, the NIH launched the Accelerating COVID Therapeutic Interventions and Vaccines (ACTIV) program, the mission of which was to develop a coordinated research response to speed treatment and vaccine options for coronavirus disease.
- Various groups were formed to tackle critical areas including a vaccine group, a preclinical group, and a clinical therapeutics group. These groups evaluated areas including development of protocols and agent prioritization.
- ACTIV subgroups were graphically summarized and comprised six groups. DAIDS was mostly involved in ACTIV-2 that is largely run by the Therapeutics Research Program in collaboration with the AIDS Clinical Trials Group (ACTG).
- The ACTIV-2 Master Protocol was summarized, and the ultimate goal was to get better therapies to advance to emergency use authorization (EUA).
- The parallel track on the vaccine and monoclonal antibody side was the Coronavirus Prevention Network (CoVPN), which was formed by networks from within the Division of AIDS -- the HVTN, the HPTN, and the IDCRC network in DMID (their infectious disease network).
- COVID-19 vaccine candidates that were evaluated were summarized. These included the Moderna vaccine that received EUA.
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. Four contract topics for the PHS 2022 solicitation to be published later this year were presented for committee approval:
- Devices and Materials to Deliver HIV-1 Broadly Neutralizing Antibodies
- Development of Long-Acting Treatments for Hepatitis C Virus (HCV) Cure
- Rapid Diagnostic Assays for Self-Monitoring of Acute or Rebound HIV-1
- Multiplexed Patient Administered Diagnostics for Hepatitis B, Hepatitis C and HIV
Q: RE: the long acting or the delivery of the bnAbs. It says for HIV, but I thought you also said there's some relevance to other viruses. Are you partnering with anyone?
A: That's a good point. Because we are the Division of AIDS, our focus is on bnAbs, but anything we learn in this space will be applicable for other infectious diseases.
Q: About the very exciting idea of a single test or platform for HIV, HPV, and HCV. Most of the value of a test is potentially for treatment of those illnesses, although prevention could be also notable. I'm wondering about PEPFAR and other organizations with a commitment to treat HPV and HCV, where we've really had a focus on HIV. Has that been considered in terms of the downstream impact of having this test available?
A: We already know we have good treatment for Hep C. We are very excited by what we see in the HPV drug development and treatment strategies. And so, what to help be a disruptive innovation (to help bring these medications along) than a simple test that could be used clinically.
Q: Monoclonal antibodies are important, bNAbs are important. And Evusheld, for SARS-CoV-2 prophylaxis, just got taken off the FDA list last week because of the emergence of new variants and sub-variants. We actually have no monoclonal antibodies now to treat or prevent--despite the pandemic preparedness not being adequately funded, can we continue to support and work on monoclonal antibodies for all infectious diseases, including SARS-CoV-2?
A: In the DMID session this afternoon, you will hear that they are interested in supporting monoclonal antibody development for diseases in the future. The NIAID Vaccine Research Center (VRC) has been committed to this as well, developing malaria monoclonal and also monoclonals for viruses like Ebola and Marburg and others. The Institute is committed to monoclonal antibodies.
Q: For SBIR topics three and four, the patient administered diagnostics have obviously been critical and very successful in the COVID response, but the flip side is, of course, now we have no idea how many infections there really are. So, is that reporting issue part of what you're thinking about here? In other words, are these just really ideally an LFA where you throw it away when you're done? Or are these something where you're hoping that there'll be reporting or connection with the health care system?
A: That needs to be worked out. The thing in coronavirus is we do have these sorts of surrogate markers called hospitalization and death. We know or I read that there's a lot of indicators, but it's not like we're completely in the dark. I think your point is for self-testing for HIV, you would ideally want there to be a health care system built around that cured patient, that if they did test positive, they had a 1-800 number or way of reaching out immediately to re-initiate therapy, go in and get a blood test, etc. I think that has to be built into the system for those kinds of tests.
NIH Office of AIDS Research (OAR) Mission-Driven Activities: Present and Future
Maureen Goodenow, Ph.D.
On behalf of the OAR, Dr. Leslie Marshall presented topics on Women's Health and HIV Research Activities at NIH.
An overview of some of OAR's new initiatives was presented. Over the past 35+ years, OAR's work has evolved. The initial research focused on HIV pathogenesis but expanded towards HIV diagnosis, treatment, prevention, cure, and improving the health of people with HIV. Critical to accomplishing the OAR mission is to understand the perspectives of people with HIV. This involves listening sessions with community partners to provide data we use to ensure that the NIH HIV research program is flexible and research priorities are responsive to emerging challenges and needs.
Some signature programs, which are current OAR priorities for HIV and HIV-related research, were described. These are:
- HIV and Aging (supported by 17 NIH Institutes, Centers, and Offices)
- HIV and Women's Health (supported by 19 NIH Institutes, Centers, and Offices)
- Technology Advances for HIV Research
- Support for Early Career Investigators in HIV Research
For 35 years, OAR has coordinated NIH's HIV research program, convening multiple partners to catalyze interdisciplinary efforts. Future directions remain the same: to end the HIV epidemic and improve the health of people with HIV. To accomplish this goal, the focus must be on action to prevent, to treat, and to cure. These actions will require continued commitment, innovation, and creativity. To reduce any efforts now would lead to the resurgence of HIV worldwide, compromising global health in the 21st century.
Q: In a pre-ARAC call with Dr. Dieffenbach, we learned that the number of K career development awards that had been funded through NIAID was smaller than it had been in recent years. How many early-stage investigator awards have been funded through all of the Institutes, and is that number also in the decline? Are there any Institutes where the number of awards has increased?
A: The overall number for HIV new investigators receiving R01 or R01-equivalents is in the range of about 60 currently at the NIH. If you use R01-equivalent as your denominator, then at the total NIH level, the percent of awards overall that are going to new investigators across the NIH is about 5 percent. Within the HIV area, it's a little under 4 percent. So, on a percentage-wise basis, we're not at the same level as the rest of the NIH.
K awards are in a different class, and I don't have those numbers at the top of my head at this moment. We can get you that information. In general, it depends on the IC which ones are funding more or less as this is definitely within the IC parameters. We can provide the data and encourage them to increase the numbers; we have been using our resources to jumpstart some new funding in this area.
Comment: Certainly, the red line that you showed on the graph with the ESIs in HIV going down while everyone else was going up was not something that any of us like to see so we'll need to think about what we can do to address that.
NIAID/DAIDS Programmatic Overview: Key Accomplishments and Future Directions
Basic Sciences Program
Diana Finzi, Ph.D.
This overview of the Basic Sciences Program (BSP) covered:
- Overview of the BSP
- HIV Scientific Highlights
- Future Directions
Two key points from the presentation:
- The depth of knowledge generated by HIV research over the past 40 years is unsurpassed by the study of any other pathogen.
- Enormous strides have been made in understanding HIV, and key insights gained on other viruses. For example, HIV laid the foundation for understanding entry of SARS-CoV-2, as well as the mRNA technology for the vaccines. Through HIV, we have learned about the complexities of the immune system.
Overview of the BSP
- 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 encourages and supports investigators who typically work on vaccines to focus on HIV vaccines but also supports a diverse range of projects.
- Collectively, BSP oversees over 550 grants with an annual budget of over $400 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.
HIV Scientific Highlights
- HIV Structural Biology: DAIDS funds six Structural Biology Centers. Lenacapavir, a new antiretroviral drug that targets and interferes with HIV-1 capsid formation, has been developed and was based on fundamental science done by Wes Sundquist at the CHEETAH (Center for the Structural Biology of HIV Infection, Restriction and Viral Dynamics) Center, investigators from other centers and importantly in collaboration with Gilead. This highlights an example of ideal collaboration between government, academia, and industry.
- HIV Cure: This area has fostered many collaborations including with IAS, the Bill and Melinda Gates Foundation and with our grantees. The ten Martin Delaney Collaboratories represent our flagship program.
- Work from the DARE (USCF) Collaboratory was reviewed that involved the development and use of FIND-Seq (Focused Interrogation of Cells by Nucleic Acid Detection and Sequencing) technology for gene expression profiling of HIV DNA+ cells. This can potentially facilitate the early detection of transcription pattern signatures associated with HIV latency.
- Ending the HIV Epidemic (EHE): A summary of this initiative, launched in 2019, was reviewed that covered its focus areas and large number of projects that it comprises.
- BSP initiatives will focus on further deepening knowledge and on details of the provirus, the virus, and how to target it very specifically by the immune system, where even the smallest changes can make a big difference in what is recognized.
- Lessons learned with COVID: leveraging what has been learned through HIV has been extremely useful scientifically in combating SARS and challenges involve drawing funding lines.
- Grantees were very eager to help solve COVID, but funding lines had to be drawn.
- Similarly, in epidemiology and ending the HIV epidemic, aims include getting a deeper understanding of what is happening on the level of the individual, trying to reach people more directly, understanding interpersonal dynamics in at-risk populations, and leading implementation science studies to protect our people using effective strategies.
Q: Lenacapavir story is super exciting and a wonderful drug that is going to cost $40,000 per patient per year with projected sales of $4 billion a year. Obviously, drug prices are getting more and more attention. Is that a part of what you consider as these programs move ahead, as public advocates for the American taxpayer?
A: Our job is discovery and the underlying basics. I agree with you that it's horrible, but that really is not anything we can do anything about.
Comment: If I go down to CVS and buy first line HIV oral therapy, in cash, it's about $48,000 a year. TLD costs $42 a year in Chennai. This has happened historically with HIV drugs, and in no other area of medicine. I think it is our collective social and global responsibility to make sure that effective new drugs become available. So, let's take that on as part of our agenda.
Comment: Re: Lenacapavir. It is interesting in the pictures that you show that in a way it's throughout the lifecycle, it's not at the very end where [HIV] capsid inhibition occurs. That is really heartening in the sense that initially in ACTG we were saying, we can't even think about this for cure or for suppression of residual viremia because everything is going to occur at the end. But to a virologist who really understands Lenacapavir's working, apparently there is a possibility, and this is going to be studied in the ACTG, of reducing even low-grade viral loads. Could it be reducing HIV DNA levels?
Comment: Re: Price. If we thought about the TDF/FTC trials, and I think this is different but the reason that there was controversy around the price of the original TDF/FTC pill from Gilead is because all the clinical trials for PrEP were funded by the NIH?
So, FEM-PrEP, VOICE, iPrEx, all of them were funded not by the drug companies, but it was really Government money that funded the big clinical trials. Lenacapavir, the CAPELLA studies has only been -- is the only major one with results to calibrate and I think it was funded by the drug companies, is that correct, not by Government? So, it's not exactly the same thing as the protests that came about with TDF/FTC pricing.
A: To the first part of your comment - the mechanism - they know exactly where it binds because they see where mutations make it ineffective. But exactly how it's working is still being looked at. One of the most interesting things is that it seems to almost accelerate the formation of the two part, the hexamer part as the core is forming. So, it's almost like it works better and therefore creates a defective particle. So, I think we will hear a lot about it in terms of the basic science.
As far as the question of the use and the costs etc., again, we do the basic science, and so that's really out of our hands. I completely agree that it's a travesty, but I think it's a political question, and not really a question for the work that we're doing.
Q: RE: FIND-Seq assay and findings. Reflecting back on all we've accomplished, DAIDS had a lot to do with developing and enabling clinical introduction of viral load assays, and our old-fashioned resistance genotyping. As these new assays (not just FIND-seq) are coming out, does DAIDS think there could be a way to provide either Core infrastructure or to enable some of your networks, maybe CFAR [selfishly] to help researchers get access to these difficult and expensive assays to push the research faster?
A: I think you're exactly right. There's a process of innovation followed by implementation, and how CFARs decide to bring it in as a Core would be a start. Networks can decide to add it. We would always be interested in this kind of innovation.
Therapeutics Research Program
Peter S. Kim, M.D.
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.
- 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 over 90 active clinical trials or trials in development. A range of contractual resources and grants are maintained to support these high-quality clinical trials and also maintains resources to support the discovery and preclinical development of new therapeutics.
Examples of this resource:
- A very large contract that is funded together with BSP. This provides gap-filling services to advanced promising therapeutic candidates for HIV and HIV associated co-infections.
- An R24 infrastructure grant called LEAP (Long-acting/Extended release, Antiviral Research Program) is a program maintained to help and facilitate the scientific community to develop long-acting formulations.
Recent Advances, Ongoing Activities, and Anticipated Priorities
Four of the main therapeutic areas of interest were described in the presentation in more detail:
- HIV and HIV-associated comorbidities
- Tuberculosis (TB)
- Pandemic response
- HIV and HIV-associated comorbidities
Long-term goals include developing new and improved treatments and associated strategies, point of care and home-based diagnostics, ART-free remission and cure, and also working with other ICs and partners to address key co-morbidities through collaborations.
Some selected advances were described:
- Nano-formulations of Dolutegravir and Bictegravir, which supports q 6-month injections in non-human primates.
- Two bNAbs, 10-1074 and 3BNC117, used to treat people with HIV. Even without ART suppression, these two bNAbs were able to effect viral suppression over a long period of time.
Ongoing Work and Future Priorities for HIV:
- Continue to work with our investigators to develop bNAb inducing vaccines, and also T-cell inducing vaccines, and then novel combinations of these different varieties of interventions.
- Research on drug resistance, bNAb resistance, and other ancillary research that is critical to ensuring that once we have these interventions developed, we will be able to rapidly move them into the bedside.
- Development of long-acting regimens, bNAbs as treatment, and novel diagnostics to improve treatment outcomes among all PLWH and ending the HIV epidemic is a continuing priority.
- TB is the leading cause of morbidity and mortality among people with HIV, and in 2021 there were over 187,000 deaths from TB just among people with HIV, not including those that don't have HIV.
- The COVID pandemic really made a big negative difference and an impact on TB overall, including in people living with HIV.
TB Long-term goals: Enable new chemoprevention strategies, develop new diagnostics and treatments for TB/HIV, and also advance clinical and observational research in regions that are most affected by TB/HIV.
Key points summarized from this area included:
- Through a discovery cohort of 435 Mtb patients, microarray studies shown to identify two distinct TB endotypes, one for treatment failure and slower time to culture conversion, and another for improved clinical outcomes.
- Colleagues at the RePORT Brazil Consortium were able to identify that there were distinct predictors for each type of unsuccessful outcome when they applied a composite of different outcome measures in their cohort.
Ongoing Work and Future Priorities for TB
- The new TB drug pipeline is the fullest it's been in the since the beginning of TB research, and there have been a number of very important advancements in TB clinical trials.
- LTBI can now be treated in less than 1 month.
- There are 16 trials ongoing to develop and evaluate novel regimens.
- Currently working with other funding partners, both at the Gates Foundation and in Europe and around the world, to develop infrastructures and structures to facilitate communication, coordination, and collaboration among the global research organizations to realize synergies across the research field.
- Two examples of important ongoing TB trials were described: SPECTRA and ACTG 5409 (RAD-TB).
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 37.7 M PLWH are co-infected with HBV and HCV.
Long-term goals in this field focus on novel treatments for hepatitis B cure, improved preventive Hepatitis B vaccine for PLWH, long-acting regimens for Hepatitis B and C, and improved diagnostics for Hepatitis B and C.
Some select advances from this area included:
- Developing long-acting anti-hepatitis B antiretrovirals that can be coupled with anti-HIV treatments. One study showed an ultralong-acting tenofovir ProTide nano-formulation that, at least in humanized mice, could achieve suppression of HBV replication for > 3 months.
- The ongoing A5379 Phase III clinical study (Bee-HIVe) showed that Heplisav-B vaccine is highly effective at inducing protective antibodies among vaccine naïve PWH.
Ongoing Work and Future Priorities for Hepatitis B
- A number of clinical trials are evaluating other novel regimens for hepatitis B cure.
- Additional work is needed in clinical observational research and in the laboratory to get a better understanding of the pathogenesis and the pathology of hepatitis B in people with HIV.
- Develop novel biomarkers that will help in the endeavor to cure hepatitis B.
- Pandemic Response
- Early in the pandemic, the goal of the group along with the ACTG, was to develop outpatient treatments for COVID-19. In this past year, the goal pivoted to develop a clinical trial for the evaluation of Tecovirimat (TPOXX) for monkeypox.
- Now, treatments have been evaluated for two novel diseases. Seven unique trials have been developed and five of these were implemented. More than ten agents were tested, in partnership with nine industry partners.
- The ACTIV-2 study is drawing to conclusion and all the participants are now in the follow-up phase with no new enrollments. Data are being analyzed and several publications have arisen from the trial. More ACTIV-2 results are expected.
- Another important study, ACTIV-2d, was presented. This Phase 3 global ACTG study, in collaboration with Shionogi, is designed to evaluate a new SARS-CoV-2 3CL protease inhibitor: Ensitrelvir (Xocova). The study compares novel COVID-19 oral antiviral agent S-217622 with placebo in non-hospitalized participants with COVID-19 (SCORPIO-HR).
The ACTG 5418 Study of Tecovirimat for Human Monkeypox Virus (STOMP) was presented. This is a Phase 3 trial of TPOXX for outpatient treatment of mpox. The study is remotely enrolling pediatric and adult patients with mpox across the U.S. We plan to open sites globally in Brazil, Peru, Argentina, Mexico, and other countries.
Lessons Learned: What worked well and opportunities for improvement
These included items that worked well such as the clinical trials designs by ACTG. Things that could be improved upon included the need for a broad global enrollment strategy. Real world evidence to inform trial designs were critical to address changing nature of the pandemic. Available surge capacity (human and structural resources) was critical to enable rapid start-up and prevent burnout.
Q: With Xocova, what's really interesting is the resistance profile is different than Paxlovid.
RE: tuberculosis. I was wondering what the resistance is like in those drugs that are at the front, phase 3 and already approved. Is that a problem?
A: It's not a global problem yet, but it's becoming a problem. For example, Bedaquiline, which is one of the new and most effective drugs that are now available for multidrug resistant TB, already has resistance in some parts of the world. We are working hard to make sure that the resistance testing that needs to be paired and developed together with drug development is happening at the same time. And we are all afraid that unless we do that, that we will lose these drugs very quickly.
Vaccine Research Program
Mary Marovich, M.D.
This overall programmatic update for the Vaccine Research Program (VRP) covered:
- VRP Mission and Organization
- U.S. Government COVID-19 Response: Update and Lessons
- HIV-1 Vaccine Strategy, Discovery, and Design
- Vaccine Concepts in Clinical Testing
- Future Directions for Vaccines
Below is a summary of the key points for each of these areas:
- VRP Mission
Develop a safe and effective HIV vaccine. VRP is comprised of three branches:
- Vaccine Translational Research Branch (VTRB)
- Preclinical Research and Development Branch (PRDB)
- Vaccine Clinical Research Branch (VCRB)
- U.S. Government COVID-19 Response: Update and Lessons
Efficacy Testing of COVID-19 Vaccine Candidates
- A representation of the Operation Warp Speed suite of vaccines that were developed under the USG was summarized. There were three major platform types used: (i) nucleic acid with the mRNAs, (ii) the viral vectors, especially the adenoviruses, and (iii) the recombinant proteins and the adjuvants. These led to highly efficacious vaccines with regulatory submissions, emergency use authorizations, licensure, and distribution in the fight against COVID-19.
- The USG COVID response and the power of leveraging NIAID's assets was extensively described. An example is the collective power and efforts of the HIV/AIDS Clinical Trials Networks and the COVID-19 Prevention Network (CoVPN).
- Things that worked well included the public private partnerships and lessons and opportunities included accelerating pandemic response funding and its distribution.
- The CoVPN3008 trial is a top trial to watch in 2023. This is a study in sub-Saharan Africa, in seven different countries, in PWH who are largely underrepresented. It is the largest Phase III efficacy trial of mRNA COVID vaccines in PWH.
- HIV Vaccine Discovery and Design Advances
NIH HIV Vaccine Strategies Update: Moving Forward
- Data supporting the feasibility of bNAb vaccines was summarized and the Ab mediated protection (AMP) study was given as an example.
- Recent findings have demonstrated that investigators are learning how to stimulate the human immune response to activate HIV bNAb precursors.
- The process of inducing bNAbs through vaccination was described. Targets to the HIV envelope are essential for this approach and several which are susceptible to neutralization have been identified.
- Naïve B-cells are primed with the chosen immunogen to ideally trigger the broadest response. These primed cells would now have to stay within the germinal center and undergo multiple rounds of affinity maturation and they also need to undergo somatic hypermutation, T-follicular help, sequential immunization and boosting. There is growing confidence that this will result in mature B-cells that can produce broadly neutralizing antibodies.
- This process was shown in published data from the IAVI G001 Phase I trial that used an eOD-GT8 60mer adjuvanted with AS01B. This immunogen was shown to activate precursor pools of VRC01-class IgG-positive B cells.
- The use of modified mRNAs that can encode complex HIV multimeric immunogens was reviewed.
- Several NHP studies in the field were summarized and included a slow priming approach which has shown promise for difficult vaccine targets, and another study that showed CMV-vaccine T-cell priming and control of SIV replication.
- Vaccine Concepts in Advanced Clinical Testing
- The VTRB role in GMP manufacturing was summarized. The goal is for them to produce the best immunogens and bNAbs translated into clinical testing through pilot GMP production. Their HIV adjuvant portfolio was also presented.
- Multiple RNA-HIV vaccine immunogens in clinic including HVTN 302 compares membrane-bound stabilized trimers versus soluble trimers.
- Three HVTN Phase 1 studies now have shown that their various approaches can elicit neutralizing antibodies.
- The NIAID HIV Ab portfolio was summarized.
- Key lessons and next steps from the published AMP study were reviewed which showed that if the virus was susceptible to the VRC-01 bnAb, they were able to prevent acquisition.
- Future Directions for Vaccines
- The current bNAb vaccines in the pipeline were listed and the first in-human CMV-HIV vaccine that's planned to start this year was highlighted.
- The general iterative vaccine design approach was summarized.
Prevention Sciences Program
Sheryl Zwerski, DNP, CRNP
The Prevention Sciences Program (PSP) overview covered:
- Program Orientation
- 2022 Accomplishment highlights
- What is next?
- Challenges and Opportunities
Extensive amounts of data and graphic information was presented that included the global number of people living with HIV, including those newly infected and the number of children, together with the number of AIDS-related deaths, the 2000-2021 global number of new infections and global distribution of new HIV infections by population for 2021.
The key points from the remainder of this presentation:
- The four PSP branches were introduced, ranging from the preclinical branch and three clinically focused branches. The others were the administrative core, a registrational trials core and a collaborative partnerships team. Significant 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 and early HIV testing and detection in infants and children.
- Current PSP programs and initiatives were summarized.
- The Comprehensive Resources for HIV Microbicides and Biomedical Prevention (CRMP II) contract will be taken over by the Resources to Advance Pediatrics and HIV Prevention Science (RAPPS) contract starting in late FY 2023. This contract serves as a platform, to provide gap filling services as we move along from the preclinical through the later clinical testing stages.
- PSP has two clinical trials networks, the HPTN and the IMPAACT network.
2022 Accomplishment Highlights
- The South Africa, Zimbabwe, and Australian regulatory authorities have approved Cabotegravir long acting (CAB-LA) for PrEP in individuals from 35 kilograms and above, which were based on the HPTN 083 and 084 studies.
- Safety and pharmacokinetics (PK) trials of HIV mAb combinations done in collaboration with the VRP are ongoing. This is a collaboration of the HVTN and the HPTN (HVTN 136/HPTN 092, HVTN 140/HPTN 101).
- Completion of the primary analysis for MTN-043 (Dapivirine ring in lactating mother and infant pairs) will be presented at the CROI meeting in February.
Pediatric and HIV Prevention Products
- RAPPS contract. Release of the RFP in March 2022. On target for award in summer 2023.
- Establishment of collaborations with worldwide stakeholders in the area of pediatric formulations.
Prevention and Treatment for Pregnant Women and Children
- Regulatory approvals of Triumeq for children down to 14 kilograms, Doravirine for children, adolescents down to 35 kilograms, and Cabenuva for treatment down to 35 kilograms.
- Collaborated with Gilead Sciences for the FDA submission of Remdesivir for pregnant women.
- Participated in Vatican/WHO/PEPFAR convened meeting to develop Rome 6 action plan to assess progress on and intensify commitment to scaling up prevention, diagnosis and treatment of HIV and TB in children and pregnant women.
- Completed enrollment of all three cohorts of MTN-042.
What is next?
Challenges for Future of HIV Prevention Research
The effectiveness of oral PrEP and CAB-LA, as well as eventual availability of the Dapivirine intravaginal ring, will drastically decrease HIV infection rates in studies, and hopefully in the population as a whole. We still need more products, more choices, and more strategies to optimally reach all those in need of HIV prevention.
- Cost effectiveness of new HIV prevention products is crucial.
- HIV non-vaccine products with longer duration of action are needed.
- Regulatory challenges with MPTs will need to be addressed.
- Expanding the ethnographic studies to better understand desire and choice, and how to best engage key populations in HIV prevention and fill early prevention gaps.
- The requirement for innovation and community partnership for engaging men and women, and new improved insight into decision making around prevention products.
Opportunities: HPTN Specific Aims
- These cover development of novel ARV-based HIV prevention methods and delivery systems, multipurpose prevention technologies (MPTs), and integrated biomedical and socio-behavioral prevention strategies.
Challenges for Future Maternal/Child Research
- Optimizing maternal and child ART and TB regimens, and improving child friendly formulations.
- In studies for product development, include pregnant and lactating women as well as adolescents and children earlier while being sensitive to their needs in planning and trial logistics.
- The developmental studies and the preclinical studies earlier need to be done, so that we can have enough information to get pregnant women and lactating women into studies, and into the clinical testing earlier.
Opportunities: IMPAACT Specific Aims
- The specific aims for IMPAACT are novel and durable treatment interventions for: HIV, and then also for TB prevention and treatment, other complications and co-infections, as well as ART-free remission.
- RAPPS contract: Contribute particularly to the pediatric formulation work.
Comment: You expressed something that I think is really important, is it the role of NIAID to help address disparities, like it is the CDC, like it is all of us as clinicians or treaters. And I would argue along with you that it is our role. It is the role in our research studies in terms of participatory inclusion and in terms of implementation and rollout. So, we're at a point where I think it has to be explicitly stated in NIAID priorities.
Comment: I do think that the pediatric community has put forward, particularly for adolescents, not that we have separate studies, but that they be included in the adult studies using weight rather than age as a cutoff, particularly around new agents. And I don't think we've gotten to that point yet, but it would be fabulous as we're asking the question in the adult trials, in the HPTN trials, to really say, is there a reason that you wouldn't use weight rather than age?
Office of Clinical Site Oversight (OCSO)
Lessons Learned from the COVID Pandemic that May Be Applied to HIV Research: A Clinical Research Site Perspective
Manizhe Payton, M.P.H.
There was tremendous fear and uncertainty at the sites during the pandemic as they were dealing with loss of staff, supply chain disruption, changing operating procedures, all while sites were also responding to their local pandemic.
Operational Components that Worked Well
- The global network of investigators was quickly engaged to facilitate development and execution of protocols to meet this emergent need.
- Investigators were able to draw on the infrastructure that we've jointly built over many years and used existing frameworks to facilitate site expansion.
- Mobilized additional site capacity. Some of the sites were able to expand or shift their current clinic footprint to accommodate both COVID and HIV patients.
- Implemented regional approaches to operationalize studies.
- NIAID long term investment in our sites allowed us to quickly pivot the sites to contribute to NIAID's emergent research priorities. Our network sites were able to move quickly to participate in NIAID-sponsored COVID research and do so with a high level of quality.
- The robust processes and infrastructure at these NIAID sites have been refined over years and result in high quality outputs and regulatory compliance.
- Simplicity of protocol was key, especially working across many sites, many of which we had never worked with before. Simplifying the protocol translated to better compliance.
- The importance of having clear, well thought through implementation plans. Sites were under extraordinary pressure, and anticipating and understanding their needs, and addressing them proactively, with clear documentation and guidance was critical in keeping sites motivated and fostering compliance.
- Strengthen technology platforms at both the sponsor and site to facilitate remote approaches to clinical trial implementation.
- Putting tools in place and having staff trained and proficient with systems, and processes for remote activity such as eConsent, remote monitoring, remote lab collection would facilitate future research.
- Strengthen linkages between academic research institutions and community-based sites.
- Partnering with ex-U.S. regulators to build relationships and identify opportunities to expedite approvals would allow the sites to get started much quicker in these settings.
- Having contingency plans in place with mechanisms that can be quickly activated to mobilize trained staff with experienced leadership and clear project planning would allow implementation of robust project plans rapidly with a high level of quality.
Q: I want to acknowledge, in particular, the work that is often not highlighted but was done to bring on the Historically Black Medical Colleges during the COVID work. Bringing on those institutions as protocol specific sites really supported the COVID-19 research response, including actively engaging with the COVID-19 prevention network trials. The impact of bringing these sites on really helped to engender trust in key communities, assisted with building and expanding trusted voices in COVID-19 science, and supported us seeing the diversity in the COVID-19 vaccine trials that we saw. Some of the feedback that I continue to hear from colleagues and communities is regarding what is happening to leverage these same institutions, and to ensure more is being done to develop key partnerships with these institutions and other minority serving institutions. Now there are six Historically Black Medical Colleges with the inclusion of Morgan State in Baltimore and Xavier University in New Orleans.
A: I think you point out a really important aspect of our ability to advance the COVID pandemic research, but also linking it back to the HIV/AIDS research. NIAID has an integrated approach to bringing on HBCUs to support NIAID research priorities. DMID, our sister Division, has worked closely bringing on some HBCUs to support some of the priorities they're working in around the COVID response. We have worked with some of the HBCUs within the CoVPN, and it's an integrated approach that we're pursuing to be able to get more experience with the HBCUs. Within the Division of AIDS, we do have a model that relies on a solicitation and a grant-based approach to supporting sites. And we would welcome them to compete in the upcoming solicitation. There is more of an integrated approach across the Institute to involving the HBCUs in the research priorities.
Office for Policy in Clinical Research Operations (OPCRO)
Lessons Learned from the SARS CoV-2 Pandemic: A Clinical Trials Operations Perspective
Carol Worrell, M.D.
Dr. Worrell provided the lessons learned from the pandemic from a clinical trials operations perspective.
OPCRO Lessons Learned – What Worked
The lessons learned and what worked were listed and included that the science was ready and all of Government brought resources to meet the challenge, the unexpected success of full-time remote working environment and associated remote technologies, and the ability and willingness of DAIDS staff to absorb and act on a steep and rapid learning curve with respect to operational models.
OPCRO Lessons Learned – What Didn't Work
This included that some things were rushed. Also, the complexity of trial design and the move away from the existing infrastructure was problematic and introduced exceptional amounts of operational complexity. As the pandemic wore on, staff attrition increased partly due to competition from industry and retirements across DAIDS.
Opportunities and Pathways Forward
Keep things as simple as possible in a very complex environment, acknowledge when things are being hurried and stick to what you know. Going forward, DAIDS and its network collaborators will continue their efforts to improve existing trial infrastructure in the context of planning for success in Ending the HIV Epidemic. This will leave us better prepared for any future pandemic. DAIDS has initiated a Working Group to identify and address gaps in all of its processes, including the use of remote technologies for clinical trial participation. DAIDS has started work with electronic systems consultants to attempt to reduce the complexity of the large number (>20) of systems required to carry out each clinical trial and to reduce the burden on users.
Q: How is DAIDS taking on the review or what kind of investment will happen with technology to do rapid deployment of trials for pandemics, for new therapeutics, to really lever up the timelines and efficiencies. I am getting bombarded by all these companies that have these really incredible platforms for doing trials across the globe. How are we going to do it better with at least that in mind?
A: By bringing the consultants on board, we're trying to address our electronic systems and our computer work, our software, etc., in a more holistic and comprehensive way. What we've done in the past is patch things, stick in new modules as needed. We have a lot of legacy systems and we've done these complex workarounds to accommodate adding new things to them. And at this point, what we would like to know is how to streamline all of that, how to make it much more efficient, how to improve the user experience, and also how to position ourselves as we move forward in the next 5 to 10 years. We're doing this in collaboration with both OCICB (NIAID's IT group), as well as ODSET, which is a new NIAID office that deals with data sharing.
Q1: I want to go back to some of the successes of the Martin Delaney Collaboratories and highlight that as a great example of interdisciplinary collaborative science. I'm wondering how the group decides when to put together big collaborative efforts to tackle problems versus funding a handful of R01s. How do you balance those decisions?
Q2: We have networks, like the HVTN and the ACTG, that have freezers full of specimens that aren't being analyzed, but therein probably lie some interesting data and results. How do you rig some of those specimens out from the networks and make them more accessible to scientists at large?
A2: That's a really important question. One of the first things I did when I got to DAIDS 25 years ago was to see if we could work out an agreement for specimen sharing with the networks. And that was, those are our specimens, you can't touch specimens until the trial is over. And so, there's a barrier that is real. But specimens are available. And I think, you know, every 5 or 10 years we advertise that these are available, not just in MACS/WIHS, ACTG. HVTN does a really good job making their specimens available and have had the processes that are up and going. But in some ways, it's partly incumbent on the networks to also advertise that these specimens are available. So, I think we all have a responsibility to do a better job.
A1: Re: the notion of what you decide to compete, like the Martin Delaney Collaboratories versus our R01s. We've had R01s in the HIV Cure space for a decade or more. Because the problem was so multidisciplinary in terms of the challenge, we felt it was essential to try a new model that would then bring in a whole range of different people. And in some ways the CHAVIs started that in the vaccine space.
Comment: I think the Collaboratories have been really successful. I would urge you to do it more in areas like aging and maybe cardiovascular disease or other important complications for people with HIV.
A2: I would agree with that, but the issue is "swim lanes." Aging is not our primary swim lane, nor is cardiovascular disease. The NIAID Division of AIDS is happy to collaborate with the NIA and with NHLBI to tackle these questions. But it is going to require partnership, and Maureen Goodenow talked about that earlier.
Public Comments: None
Ballot Voting Outcome:
All four of the SBIR Contract Topics were unanimously approved by the Committee.
The meeting of the Council adjourned at 4:34 p.m., on Monday, January 30, 2023.
We do hereby certify that, to the best of our knowledge, the foregoing minutes are accurate and complete.
Hugh Auchincloss, M.D.
Chair, National Advisory Allergy and Infectious Diseases Council
Acting Director, National Institute of Allergy
and Infectious Diseases
Kelly Poe, Ph.D.
National Advisory Allergy and Infectious Diseases Council
Acting Director, Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Council will formally consider these minutes at its next meeting; any corrections or notations will be incorporated in the minutes of that meeting.