NIAID Council Minutes—January 27, 2020

The 194th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened at 10:00 a.m. on Monday, January 27, 2020, in Conference Rooms E1/E2, Building 45, National Institutes of Health. Dr. Anthony S. Fauci, director, National Institute of Allergy and Infectious Diseases (NIAID) presided as chair.

In accordance with the provisions of Public Law 92-463, the meeting was open to the public from 10:00 a.m. to 10:45 a.m. and from 1:00 p.m. to 4:35 p.m. The meeting was closed to the public from 8:30 a.m. to 10:00 a.m. and from 10:45 a.m. to 11:00 a.m. for review and consideration of individual grant applications. Notice of the meeting was published in the Federal Register.

Meeting Attendees

Member Group

Present

Absent

Council Members

  • Dr. Raul Andino
  • Dr. Ritu Agarwal
  • Mr. Elling Eidbo
  • Dr. Mark Feinberg
  • Dr. Ana Fernandez-Sesma
  • Dr. Amita Gupta
  • Dr. Sally Hodder
  • Dr. Marc Jenkins
  • Dr. Stanley Lemon
  • Dr. Robin Patel
  • Dr. Gwendalyn Randolph
  • Dr. Anuradha Ray
  • Ms. Kay Whalen
  • Dr. Cara Wilson
  • Dr. Michael Brenner

Ad Hoc Members

  • Dr. Peter Nickerson
  • Dr. Qizhi Tang
 

Ex Officio Members

  • Dr. Jay Butler
  • Dr. Victoria Davey
  • Dr. Anthony Fauci
  • Lt. Col. Wendy Sammons-Jackson
 

NIAID Senior Staff

  • Dr. Hugh Auchincloss
  • Dr. Carl Dieffenbach
  • Dr. Emily Erbelding
  • Dr. Matthew Fenton
  • Dr. John McGowan
  • Dr. Daniel Rotrosen
 

Table of Contents

I. Review of Grant Applications
II. Remarks of the Director, NIAID—Anthony S. Fauci, M.D.
III. Report of the Allergy, Immunology, and Transplantation Subcommittee—Daniel Rotrosen, M.D., director, DAIT
IV. Report of the Microbiology and Infectious Diseases Subcommittee—Emily Erbelding, M.D., M.P.H., director, DMID
V. Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)—Carl Dieffenbach, Ph.D., director, DAIDS
VI. Adjournment

I. Review of Grant Applications

The National Advisory Allergy and Infectious Diseases Council convened in closed session to consider applications in allergy and immunology, microbiology and infectious diseases, and AIDS. 

Funding Actions: The Council reviewed 4,574 research and training applications with primary assignment to NIAID for a requested amount of $1,957,780,188 in first-year direct costs and recommended approval of 1,923 applications with $675,317,645 in first-year direct costs.

II. Remarks of the Director, NIAID—Anthony S. Fauci, M.D.

Dr. Fauci opened the Council session by welcoming visitors to the meeting. He introduced two new Council members: Dr. Ritu Agarwal, interim dean at the Robert H. Smith School of Business at the University of Maryland, and Mr. Elling Eidbo, current board member of Donate Life America and most recently the former CEO of the Association of Organ Procurement Organizations.

He also introduced two ad hoc Council members: Dr. Peter Nickerson, vice dean of research at the University of Manitoba, and Dr. Qizhi Tang, director of the Transplantation Research Laboratory at the University of California, San Francisco. 

Council member Dr. Michael Brenner was unable to attend the meeting.

Consideration of Minutes of Previous Meeting

Council considered the minutes of the September 9, 2019 meeting and concepts that had been presented and approved them as written.

Appointments and Transitions

In December, Dr. Stephen Hahn was sworn in as the 24th commissioner of the Food and Drug Administration. Before joining FDA, Dr. Hahn served as the chief medical executive at the University of Texas, MD Anderson Cancer Center. He takes over for Acting Commissioner Dr. Ned Sharpless, who returns to his previous position as director of the National Cancer Institute. 

Dr. Joshua Denny has been selected as CEO of the "All of Us" Research Program. As CEO, he will oversee NIH's efforts to build one of the most comprehensive precision medicine research platforms in the world in partnership with a diverse network of awardees and participants.

Staff and Organizational Changes

Dr. Peter Jahrling recently retired as chief scientist and director of NIAID’s Integrated Research Facility at Fort Detrick in Frederick, Maryland. Dr. Connie Schmaljohn is the new chief scientist and director of the Integrated Research Facility. 

Dr. Julie Ledgerwood has been named deputy director and chief medical officer of NIAID’s Vaccine Research Center. 

In the Division of Microbiology and Infectious Diseases (DMID), Dr. David Mc Neeley is the new director of the Office of Regulatory Affairs.

Sharon Gilles has joined NIAID’s Office of the Director as special assistant to Principal Deputy Director Dr. Hugh Auchincloss.

In the Division of Extramural Activities, Dr. Kelly Poe has been selected as the new deputy director of the Scientific Review Program, and Stanley Knight was recently promoted to chief of the MID Research Contracts—Branch A in the Office of Acquisitions.

Meetings and Events

Dr. Ian Wilson of The Scripps Research Institute in La Jolla delivered the Kinyoun lecture on November 19. In his talk titled Structure Assist and Design of Universal Vaccines and Therapeutics Against Influenza Virus, he explained how insights gained through structural biology are aiding in devising new ways to treat or prevent influenza.

On December 20, NIH and the Bill and Melinda Gates Foundation held the sixth annual consultative workshop. Topics of interest that were discussed included HIV/AIDS, malaria, tuberculosis, Ebola, enteric diseases, and epidemic preparedness.

Several international delegations and health officials visited NIAID over the last several months. Dr. Fauci met with Dr. Ekaterine Tikaradze, the minister of health of Georgia; leadership from the University of Sciences, Technology, and Techniques of Bamako, Mali; and a Japanese delegation that participated in the U.S.-Japan Medical Biodefense Research Symposium.

Budget Update

The President’s Budget for fiscal year (FY) 2021 is expected to be submitted to Congress on February 10. 

Congress approved a spending package for FY 2020 that the President signed into law on December 10. NIH received a $2.6 billion increase from FY 2019, which makes this the fifth consecutive year that NIH has received a significant increase.

NIH received an overall increase of 6.7 percent. NIAID received a 6.6 percent increase, which included $50 million for combating antimicrobial resistance and $60 million for developing a universal influenza vaccine. 

Dr. Fauci summarized NIAID’s FY 2020 financial management plan. Our R01 payline is set at the 14 percentile for established principal investigators (PIs) and the 18 percentile for new PIs. NIAID does not plan to make programmatic cuts to noncompeting and competing grants. Competing research initiatives were cut up to 10 percent from their planned budget level. Our estimated success rates for research project grants will be 22 to 24 percent.

Legislative Update

Dr. Fauci outlined some leadership changes to committees in Congress. On October 17, Representative Elijah Cummings, a democrat from Maryland, passed away. He represented the Congressional district encompassing most of Baltimore and served as chair of the House Committee on Oversight and Reform. Representative Carolyn Maloney of New York replaces him as Committee chair. 

Representative Nita Lowey of New York and chair of the House Appropriations Committee will retire at the end of the 116th Congress. She has been a good friend and supporter of NIH. 

On October 2, Dr. Fauci received the AIDS United Public Policy Council's inaugural award for Leadership in HIV Policy and Research during its Congressional reception. 

On October 23, Dr. Fauci accompanied HHS Secretary Alex Azar to brief leadership of several Senate and House Committees on the U.S. government delegation to the Democratic Republic of the Congo (DRC), Rwanda, and Uganda where they observed the Ebola outbreak response on the ground in the DRC. Dr. Fauci also participated in a third briefing of additional members of the House Energy and Commerce Committee.

On November 20, Dr. Fauci testified before the House Committee on Science, Space, and Technology at a hearing focused on innovations in influenza vaccines, and on December 4, he testified before the House Energy and Commerce Oversight and Investigations Subcommittee at a hearing on influenza preparedness and response. At both hearings, he updated committee members on recent advances in NIAID research to develop universal influenza vaccines. 

On December 5, Dr. Fauci participated in a Congressional briefing hosted by NMAC, formerly known as the National Minority AIDS Council, in partnership with the House Congressional Caucus on HIV/AIDS, Congressional Black Caucus, Congressional Hispanic Caucus, Congressional Asian Pacific American Caucus, and Congressional LGBT Caucus. He outlined NIAID’s role in the federal plan to end the domestic HIV epidemic and presented some of the latest advances in treating HIV/AIDS.

On January 24, Dr. Fauci participated in a full bipartisan Senate briefing organized by Senate Health, Education, Labor, and Pensions, and Foreign Relations Committees on the recent outbreak of the novel coronavirus in China. He briefed them on efforts to develop and test a candidate vaccine as well as research on potential therapeutics.

Dr. Fauci thanked NIAID leadership and staff who have participated in Congressional briefings and events on influenza vaccine development, Valley fever, and Lyme and other tickborne diseases.

Other Information Items

Dr. Fauci began by noting that NIAID staff have been working with other colleagues on developing strategic plans and research agendas for two important multi-institute initiatives:

He provided an update on Ebola, which included statistics on the number of confirmed cases and deaths related to the outbreak in the Democratic Republic of the Congo (DRC), and a summary of the results of the randomized, controlled trial of Ebola therapeutics.

In September, HHS Secretary Alex Azar, Dr. Fauci, CDC Director Dr. Bob Redfield, and officials from HHS, USAID, and the National Security Council traveled to the actual site of the study in the DRC to assess the Ebola response efforts. 

Dr. Fauci summarized the ring vaccination study used to control the spread of Ebola in the DRC outbreak. The vaccine has shown to be effective and has been given the European Commission first-ever market authorization. The World Health Organization prequalified the vaccine, paving the way for use in high-risk countries, and FDA approved the vaccine for the prevention of Ebola virus disease.

Dr. Fauci highlighted some recent HIV/AIDS events. On October 7, Harvard Law School had a symposium reflecting on 15 years of PEPFAR, and on November 25, an event was held at the National Academy of Sciences to celebrate World AIDS Day and review the challenge of ending the HIV epidemic in the United States. He noted the Plan for Ending the HIV Epidemic, the current HIV treatment and prevention toolkits, and the roles the different HHS agencies have in the plan. 

NIH and the Gates Foundation are working on a plan to bring gene-based treatments for HIV and sickle cell disease to Africa, and each plan to contribute about $100 million over four years to this effort.

Dr. Fauci gave an update on influenza. The President invited Dr. Fauci, HHS Secretary Alex Azar, and HHS Assistant Secretary for Preparedness and Response Dr. Robert Kadlec to the White House when he signed the Executive Order on modernizing influenza vaccines to promote national security and public health. This is part of the effort to develop a universal influenza vaccine, along with our Comprehensive Program for Universal Influenza Vaccine Development and our new Infectious Diseases Clinical Research Consortium. 

He provided brief summaries on recent developments in the areas of tuberculosis, acute flaccid myelitis, measles, and eastern equine encephalitis. 

Dr. Fauci concluded with an update on the 2019 novel coronavirus, which included a timeline of the early events in the epidemic, China’s response to the outbreak, and a summary of the U.S. situation and precautions that are being taken. 

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

Dr. Rotrosen welcomed the subcommittee members to the 194th meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting. 

Dr. Rotrosen presented the following scientific and Division activities:

Staff and Organizational Changes

Patricia Rohan, M.D., Dr. Rohan joined the Autoimmunity and Mucosal Immunology Branch in October 2019, as a medical officer in the Rheumatologic Autoimmune Diseases Section. She attended medical school at Creighton University in Omaha, Nebraska, and completed an internal medicine residency and fellowships in Rheumatology and in Allergy and Immunology at the University of Kansas Medical Center, Kansas City, Missouri, before moving to the East Coast to do a biotechnology fellowship at NIH/NCI in Bethesda, Maryland. Her long career at FDA included a position at the Center for Food Safety and Applied Nutrition, Office of Special Nutritionals, and three positions at the Center for Biologics Evaluation and Review in the Office of Blood Research and Review, Office of Vaccines Evaluation and Review, and Office of Biostatistics and Epidemiology.

Lisa Gaglis, R.N., B.S.N., Ms. Gaglis joined the Allergy, Asthma, and Airways Biology Branch (AAABB) in January 2020 as a nurse consultant/project manager. Lisa received her B.S.N. from the University of New Hampshire and began her career as a bedside nurse at the Brigham and Women’s Hospital in Boston. Thereafter, she transitioned into clinical research at Boston University where she worked as a clinical research nurse and, since 2007, as a clinical research project manager, providing operational oversight for the research team responsible for a number of NIAID-funded studies conducted over the past 12 years by the Inner-City Asthma Consortium. Her experience with clinical protocol and operations manual development, staff training, and safety oversight will be put to good use as a member of the AAABB team.

Division Activities

Allergy, Asthma, and Airway Biology Branch

2019 Annual Asthma and Allergic Disease Cooperative Research Center Face to Face Meeting (AADCRC). On October 29 and 30, 2019, NIAID sponsored the 14th annual face-to-face meeting of the AADCRC investigators in Rockville, Maryland. The one-and-a-half-day meeting of principal investigators (PIs), co-investigators, students, and program staff included oral and poster presentations from the 11 NIAID-funded research Centers, as well as three NIAID-funded Program Project grant teams, and a special session featuring the work of AADCRC opportunity fund-supported young investigators.

Clinical Research Needs for the Management of Chronic Rhinosinusitis with Nasal Polyps in the New Era of Biologics. On November 4 and 5, 2019, the NIAID-organized a workshop in Rockville, Maryland, to discuss the current state of knowledge on the management of chronic rhinosinusitis (CRS) with nasal polyps, particularly with regards to new potential biologic treatments. The objective of the workshop was to obtain expert input on clinical trial design, including identification of appropriate patients and development of appropriate treatment algorithms for the use of biologics for the medical management of CRS with nasal polyps. Experts discussed epidemiology, the economic impact of CRS, treatment targets and disease management strategies, measures of disease severity and treatment success, and optimal study designs for future trials. A manuscript to summarize the conclusions of the workshop is planned.

Basic Immunology Branch

Immune Mechanisms of Wound Healing in the Elderly. On September 23 and 24, 2019, NIAID and National Institute of Aging (NIA) hosted a workshop to discuss the current state of the science and to identify knowledge gaps and challenges in understanding how age-related immune changes in the elderly affect wound healing during infection or in conjunction with metabolic or inflammatory disease. Investigators supported by NIAID and the NIA discussed the complexity of chronic wounds, the models currently available for investigating immune contributions in chronic wound pathology and resolution, drivers of dysregulated wound repair, dynamics of the aging host-microbe relationship, and models and mechanisms of tissue repair. Cross-disciplinary discussions and new collaborations ensued from the workshop.

Collaborative Influenza Vaccine Innovation Centers (CIVICs) Kick-Off Meeting. On October 23 and 24, 2019, a kick-off meeting was held in Rockville, Maryland, to bring together the contractors and NIAID staff involved in this large new program that is jointly managed by DAIT and DMID. The purpose of the program is to develop improved influenza vaccines that are both efficacious and broadly protective, as outlined in NIAID’s universal influenza vaccine strategic plan. The CIVICs program will generate novel vaccine candidates, perform preclinical testing and validation of candidates, and manufacture and test candidate vaccines in clinical trials, including human challenge studies. Detailed immunologic analyses will be conducted on the preclinical and clinical samples to further improve the vaccines and identify correlates of immune protection. Data from the program will be managed by a statistical and data management coordination center. The meeting enabled the principal investigators to meet in person and develop collaborations and synergies.

Maintaining Immunity After Immunization Kickoff Meeting. On October 25, 2019, the kickoff meeting of the Maintaining Immunity after Immunization program was held in Rockville, Maryland. This 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 overview of their projects, briefly report any progress, and to develop scientific collaborations with each other to foster program success.

Molecular Mechanisms of Combination Adjuvants (MMCA). On November 7, 2019, NIAID held the annual meeting of the Molecular Mechanisms of Combination Adjuvants Program in Rockville, Maryland. MMCA investigators provided research program and collaborative supplement updates and planned future collaborative projects to maximize utilization of resources and complementary expertise. In addition, a guest speaker presented on the use of the Cationic Adjuvant Formulation adjuvant system for combining adjuvants targeting multiple innate pathways.

Immune Epitope Database and Analysis Resource (IEDB) User Meeting. On November 7 and 8, 2019, the annual User Meeting was held in the Rockville, Maryland, organized and led by staff from the IEDB, with coordination from NIAID, for the purpose of training the meeting attendees to better utilize the database interface and analysis tools software. There were approximately 45 participants in the meeting over 2 days and 13 investigators were provided travel support under the IEDB contract. Post-meeting analysis showed a very high level of enthusiasm and positive feedback from participants. 

Immune Mechanisms of Protection Against Mycobacterium Tuberculosis Centers (IMPAc-TB). On November 12, 2019, the kick-off meeting for the IMPAc-TB program was held in Rockville, Maryland. Three IMPAc-TB contracts were awarded in FY 2019 with the goal of identifying and characterizing immune responses required to protect a host from initial Mycobacterium tuberculosis infection, establishment of latent infection or progression to active tuberculosis (TB) disease. The studies will use small animal, nonhuman primates and human models, functional assays and systems immunology approaches to facilitate the development of improved vaccine strategies. IMPAc-TB is the first NIAID trans-divisional program supporting studies to better understand TB immunology. 

Annual Adjuvant Development Program Meeting. On November 19 and 20, 2019, the annual meeting of the NIAID Adjuvant Development program was held in Rockville, Maryland. The NIAID Adjuvant Development program is supporting six research groups that are developing and optimizing Toll-Like Receptor agonists and Outer Membrane Vesicles as vaccine adjuvants, within the context of enhancing vaccines to protect against influenza, B. pertussis, M. tuberculosis, flaviviruses (Dengue, Zika, West Nile Virus), Y. pestis, and Shigella. The goal of the meeting was for the research teams to report on their progress in the development of lead vaccine adjuvants and to enhance collaborations across the groups. The meeting also included a guest speaker from the Bill & Melinda Gates Medical Research Institute who described their interest in vaccine adjuvants and their availability to the community.

Human Immunology Project Consortium (HIPC) Subcommittee Meeting. On November 21, 2019, the HIPC Assay, Bioinformatics and Clinical Subcommittees met in Rockville, Maryland, to discuss ongoing activities and develop future projects. The mission of these Subcommittees is to promote HIPC program goals and foster collaboration amongst HIPC investigators. Current activities include development of clinical meta-data standards and improvements to immune cell representations in the Cell Ontology, in collaboration with the Cell Ontology community. These activities will facilitate date submission to the ImmPort and ImmuneSpace websites and date reuse/mining by both HIPC investigators and the broader research community. Several HIPC investigators also are developing an immune signatures knowledgebase, where they have curated vaccine-related immune signatures within ImmPort and from the published literature for public use/comment: hipc-dashboard.org.

Immunity in Neonates and Infants Annual Meeting. Investigators awarded under the Immunity in Neonates and Infants program met on December 11 and 12, 2019, in Rockville, Maryland. Fifteen projects are supported under this program that is a partnership among NIAID, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Environmental Health Sciences. Investigators reported current progress on their projects that included data on infant immune regulatory mechanisms to allergens, commensal bacteria, vaccines, infections (including HIV) or environmental pollutants. New collaborations and discussions were initiated to leverage resources and complementary expertise to advance the field. 

Cooperative Center for Human Immunology (CCHI) Program. On December 18 and 19, 2019, the kick-off meeting of the DAIT CCHI Program was held in Bethesda, Maryland. The program supports mechanistic and hypothesis-testing studies to understand human immunity applicable to the biodefense effort, i.e., innate, adaptive, and mucosal immune responses to infection, vaccination, and adjuvants. The renewed program is composed of eight centers. At the meeting, the PIs and associated researchers from each center presented their overall research plan for the next five years. They also identified tangible resources, capabilities, and needs to advance overall program goals. The Steering Committee (which includes the PIs of all the centers) met with Program Staff to discuss business issues, scientific advances, and plans for the coming year.

Autoimmunity and Mucosal Immunology Branch

ACE Steering Committee Meeting. On October 30 and 31, 2019, NIAID and the Autoimmunity Centers of Excellence (ACE) organized a meeting in Rockville, Maryland. They reviewed and approved Collaborative Projects with three overarching themes: 1) regulation of B cell and T cell tolerance across several different autoimmune diseases, 2) sub-setting of lupus patients to understand pathogenesis and appropriately direct therapies, and 3) obtaining a better understanding of the contributions of adaptive immune cells and stromal cells to autoimmune diseases that lead to target organ remodeling. They also drafted and have now finalized the ACE Research Agenda, which covers the entire program including clinical trials, Center projects, pilot projects, and the Collaborative Projects.

Concepts Presented for Clearance

FY 2021 SBIR Contract Topics Discussed at Council

  • Adjuvant Development for Vaccines and for Autoimmune and Allergic Diseases
  • Adjuvant Discovery for Vaccines and for Autoimmune and Allergic Diseases
  • Production of Adjuvants Mimics
  • Reagents for Immunologic Analysis of Non-mammalian and Underrepresented Mammalian Models

FY 2021 Research Concept Clearances

Clinical Trials in Transplantation in Children and Adults (U01, Clinical Trial Required)
This initiative will support multicenter clinical trials, with associated studies of immune mechanisms, in heart, lung, kidney, liver, and intestinal transplantation; clinical trials of non-hematopoietic cellular transplantation as replacement therapies, such as pancreatic islets or hepatocytes; vascularized composite tissue transplantation; and transplantation of bone marrow or of immunologically active cells, as adjuncts to any of the foregoing; and trials that focus on infectious disease in transplant recipients.

The subcommittee endorsed and unanimously approved this initiative.

Mucosal Immunology Studies Team (U01, Clinical Trial Not Allowed)

To support basic research projects on immune defense and immune regulation at respiratory, gastrointestinal, and urogenital tract mucosal surfaces. The long-term goal is to develop the knowledge base needed to design therapeutics and mucosal vaccines and therapeutics for mucosal-initiated immune-mediated disease and inflammation, and mucosal infections.

The subcommittee endorsed and unanimously approved this initiative.

Nonhuman Primate Reagent Resource (U24, Clinical Trial Not Allowed)

The objective of the Nonhuman Primate (NHP) Reagent Resource is to facilitate the optimal use of NHP models in vaccine and adjuvant development, infectious and immune-mediated diseases, and transplantation by developing and providing reagents for 1) in vitro monitoring immune parameters, 2) in vivo modulation of the immune response, and 3) conducting immune-based mechanistic studies.

The subcommittee endorsed and unanimously approved this initiative.

FY 2022 Research Concept Clearances

Allergy & Asthma Statistical, Monitoring and Coordinating Center

The Allergy & Asthma Statistical, Monitoring and Coordinating Center will provide biostatistical support for protocol development and analysis and for study publications resulting from clinical trials and studies conducted by DAIT-funded collaborative networks and for investigator-initiated studies within the Allergy, Asthma, and Airways Biology Branch.

The subcommittee endorsed and unanimously approved this initiative.

Transplantation Statistical, Monitoring and Coordinating Center

The Transplantation Statistical, Monitoring and Coordinating Center will provide biostatistical and monitoring services throughout the three phases of clinical trial management: 1) protocol development and site initiation, 2) patient enrollment, investigational arm assignment, last-patient-last-visit, and 3) database lock, data analysis, and study close-out.

The subcommittee endorsed and unanimously approved this initiative.

Autoimmune Diseases Statistical, Monitoring & Coordinating Center

The Autoimmune Diseases Statistical, Monitoring & Coordinating Center will provide clinical study development, management, site monitoring, repository management, manuscript production, study archiving and biostatistical support for clinical trials in the areas of autoimmune diseases and primary immune deficiencies while maintaining and supporting all relevant regulatory requirements.

The subcommittee endorsed and unanimously approved this initiative.

IV. Report of the Microbiology and Infectious Diseases Subcommittee—Emily Erbelding, M.D., M.P.H., director, DMID

Director’s Report

Dr. Emily Erbelding, director of the Division of Microbiology and Infectious Diseases (DMID), chaired the NIAID Microbiology and Infectious Diseases Council Subcommittee meeting on January 27, 2020. Dr. Erbelding thanked Dr. Raul Andino for his service on the DMID Subcommittee, noting that his term had been extended for an additional Council meeting. She also provided a DMID personnel update, recognizing new staff appointments made in the Division since the last Council meeting, including: Nancy Ulbrandt, Michael Kozar, and Clint Florence, Office of Biodefense, Research Resources, and Translational Research; Reed Shabman, Office of Genomics and Advanced Technologies; Brittany Woods, Enteric and Sexually Transmitted Infections Branch; Ruth Florese, Virology Branch; Rebecca Lampley, Respiratory Diseases Branch; and Guinevere Chun and Tatiana Beresnev, Office of Clinical Research Affairs. She also noted the appointment of Mark Challberg as the chief of the Virology Branch and the retirements of Pat Repik, Virology Branch, and Katrina Gross, Office of Scientific Coordination and Program Operations.

Following staff introductions, Dr. Erbelding reported on several recent DMID scientific activities: 

  • The results of a Phase 3 efficacy trial of the Takeda dengue vaccine were recently published in the New England Journal of Medicine. The vaccine was found to be efficacious in preventing dengue fever in children and adolescents living in dengue-endemic countries and well tolerated with no significant safety concerns identified in analyses to date. She noted that DMID supported this vaccine extensively in preclinical and early clinical development, funding the first Phase 1 trial as well as a Phase 1B trial to test delivery through a needle-free device.
     
  • Melioidosis is the third leading cause of death from infectious diseases in Northeast Thailand and is also prevalent in other parts of Southeast Asia. DMID support contributed to the development of the first point-of-care diagnostic for melioidosis.
     
  • The second vaccine that has been deployed in the Ebola outbreak in the Democratic Republic of the Congo (DRC), the Ad26.ZEBOV/MVA-BN vaccine by Johnson & Johnson, received significant support from DMID in its early phases of preclinical development, and to some degree during the clinical development phase. Eleven thousand doses of vaccine were shipped to the DRC and are being evaluated in a clinical trial designed to assess the efficacy of the vaccine in an outbreak setting.
     
  • NIAID announced a new Leadership Group affiliated with the recently renewed Vaccine and Treatment Evaluation Units, which together will create the new Infectious Disease Clinical Research Consortium (IDCRC). The Leadership Group was awarded to Emory University, and the co-PI is affiliated with the University of Maryland. The IDCRC recently held a kickoff meeting and is currently developing and prioritizing clinical concepts for development and implementation.
     
  • NIAID renewed the Antibacterial Research Leadership Group award to Duke University. Their focus in the next seven years will be on improving treatment for resistant gram-negative infections and improving diagnostics to better guide antibiotic treatment.
     
  • NIAID updated the 2014 report titled “NIAID’s Antibiotic Resistance Research Framework: Current Status and Future Directions” in December 2019. The new report is posted on the NIAID website.
     
  • Awards were made in late September 2019 to establish the Collaborative Influenza Vaccine Innovation Centers program, which will focus on developing broad and more durably protective vaccines against influenza.

Dr. Erbelding also reported that DMID will be joining a FY 2021 Division of Allergy, Immunology, and Transplantation-led concept entitled “Clinical Trials in Organ Transplantation in Children and Adults,” which will support cooperative, multi-institutional consortia for the conduct of interventional trials (Phase 1, 2, or 3) or observational clinical studies in organ, vascularized composite tissue, or cellular replacement allotransplantation. The concept includes a specific emphasis on and funding for studies of infectious disease in transplant recipients.

Finally, Dr. Erbelding presented five topics for inclusion in the 2021 Small Business Innovation Research (SBIR) Contract Solicitation for the Subcommittee’s consideration:

  1. Pediatric Formulations of Select Second Line Drugs for Treating Tuberculosis–to develop innovative, pediatric-friendly, oral formulations for select second line drugs that are approved for treatment of TB.
  2. Rapid, Point-of-Care Diagnostics for Hepatitis C Virus–to develop a point-of-care diagnostic for primary health-care settings to detect active, viremic HCV infections in a single visit and to confirm cure following treatment.
  3. Development of Priority Diagnostics for Chagas Disease–to develop a sensitive and specific rapid point-of-care diagnostic assay; or to develop a biomarker-based Test of Cure (ToC) to evaluate treatment outcome.
  4. Improving Technologies To Make Large-Scale High Titer Phage Preps–to develop generalizable procedures and necessary tools to manufacture and purify stable high titer phage stocks suitable for use in clinical trials.
  5. Group A Streptococcus (GAS) Vaccine Development–to develop GAS vaccine candidates that are suitable for future advanced development. This topic will support preclinical development and standardization of methods for evaluation of GAS vaccine candidates.

All topics were approved.

Update: NIAID Interagency Interactions on Antimicrobial Resistance–Dr. Dennis M. Dixon, chief of DMID’s Bacteriology and Mycology Branch (BMB), provided an overview of DMID interactions with other federal agencies to address antimicrobial resistance. He noted that many of these efforts are guided by activities established in 2014 under an Executive Order from the President focused on Combating Antibiotic-Resistant Bacteria (CARB). This action required federal departments and agencies to form a Task Force for Combating Antibiotic-Resistant Bacteria, which was charged with implementing the National Strategy on Combating Antibiotic-Resistant Bacteria (CARB) through the development of a National Action Plan that mandates specific federal actions over a five-year period. These efforts are guided by an advisory committee focused on CARB, which meets several times per year to discuss ongoing activities of the member agencies. These meetings help increase awareness of agency efforts and facilitate ad hoc discussions about possible areas of collaboration. Within DMID, Dr. Dixon described how extramural CARB activities are supported, starting at the very basic science level within BMB and moving forward to DMID’s Office of Biodefense, Research Resources, and Translational Research where candidate products are poised for advanced development and possible hand-off to the HHS Biomedical Advanced Research and Development Authority (BARDA). Dr. Dixon highlighted several examples of products that DMID has supported from early through translational development stages, and discussed how DMID staff engage with companies, BARDA and other agencies to help advance these products as warranted. Finally, he described the ongoing CARB-X program, a global public-private partnership to bolster innovation in antibacterial product development launched by BARDA in 2016 to accelerate the development of products focused on the most serious drug-resistant bacteria. DMID participates in this effort with BARDA and other partners, providing drug development expertise and preclinical testing services to CARB-X awardees. CARB-X engagements provide further opportunities for DMID staff to collaborate with other Federal agencies to advance antibacterial development.

Update: Addressing Evolving Needs in Malaria R&D–Dr. Lee Hall, chief of DMID’s Parasitology and International Programs Branch, provided a brief update on the current global malaria situation, noting that progress in reducing new malaria cases globally has leveled off and that in some areas the number of new cases is on the rise. As a result, new and enhanced global control efforts will be required to restore momentum. While recent reports from both a Lancet Commission and the WHO Strategic Advisory Group of Experts on Malaria Eradication concurred that malaria eradication remains an appropriate long-term goal, he noted that currently available control and elimination efforts have limitations which may impede future progress towards eradication. As described by Dr. Hall, recent research advances supported by NIAID, however, have laid the foundation for identification, development, and eventual deployment of novel interventions to ensure that elimination and eradication efforts remain viable. He provided illustrative examples of several exciting NIAID advances spanning the following categories: basic research/genomics, diagnostics, therapeutics, vaccines and other immunoprophylaxis, vector control strategies, and clinical and field research. 

Concepts Presented for Clearance

The following FY 2021 concepts were presented to the Subcommittee:

Limited Competition: National Biocontainment Laboratories Operations Support–The objective of this concept is to provide continued operational support for the National Biocontainment Laboratories (NBLs) at the University of Texas Medical Branch (UTMB) and Boston University (BU), enabling them to develop and maintain resources and facilities necessary to meet national, regional, and local biodefense and emerging infectious diseases Biosafety Level 4 (BSL4) research needs. The Subcommittee members stressed the importance of NIAID continuing to provide operational support to the two NBLs as it is not possible for a BSL4 laboratory to evolve to ‘self-sustaining’ due to the extraordinary costs required. Program staff emphasized that although the support provided by NIAID is significant, it is recognized that it does not cover one hundred percent of the costs associated with operating the BSL4 laboratories, and thus it is expected that the universities are also committed to ensuring these laboratories remain functional. Subcommittee members expressed concern that equipment was likely aging in the facilities and would need to be replaced. Program staff stated that the NBLs are required to include a preventive maintenance plan for the lifecycle replacement and repair of critical equipment and systems unique and necessary for operating a BSL4 laboratory (e.g., breathing air, effluent decontamination system, chemical showers), as well as non-routine emergency repairs of BSL4 equipment and systems.

In addition, Council members wanted to better understand how research is prioritized in the NBLs, especially during times of high need (i.e., emerging infectious disease outbreaks). Program explained that if a new, unaddressed priority emerges, NIAID program staff work closely with the NBLs to coordinate activities and prioritize studies in the queue. As BSL4 capacity is indeed limited, especially during an outbreak, NIAID also relies on the larger network of BSL4 laboratories. Program stated that the UC7 is a cooperative agreement mechanism and within the terms of the award, during an event and/or an outbreak, NIAID priorities take precedence over other activities. Nonetheless, program acknowledged that no formal process exists for the prioritization of studies within the NBLs, and that staff would evaluate if such a process could be developed that would increase efficiency while keeping within the current terms of award.

Three-Dimensional Human Biomimetics for Infectious Diseases–The objective of this concept is to develop new and advance existing human-derived three-dimensional (3D) models to facilitate infectious diseases research. Ultimately, these models can be used to advance the development of new drugs. Subcommittee members voiced support for the Three-Dimensional (3D) Human Biomimetics for Infectious Diseases concept. One of the Subcommittee reviewers noted that this was a cutting edge and timely concept that is needed for many pathogens and can fill specific gaps in infectious diseases. Moreover, another Subcommittee member stated that the development of 3-D human-cell or -tissue derived models is within the realm of possibility; a sufficient body of work shows that these ideas are no longer “science fiction.” Three-dimensional human-derived models are a viable and exciting alternative to animal models, as they better reflect actual physiologic conditions and allow the performance of more replicates under more conditions. As such, these models represent a bridge between animal models and the human host. The Subcommittee emphasized the importance of innate immunity and the benefit of understanding immunology in a non-immunocompromised system. In addition, Program should explicitly define responsive versus nonresponsive research in any potential initiative.

All concepts were unanimously approved.

V. Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)—Carl Dieffenbach, Ph.D., director, DAIDS

Welcome and Approval of Minutes

Kenneth Freedberg, M.D. (Chair)

Dr. Freedberg welcomed everyone and the ARAC members approved the minutes of the September 2019 meeting.

Director’s Report and SBIR Contract Topics

Carl Dieffenbach, Ph.D.

Dr. Dieffenbach introduced new committee members: Kenneth Freedberg, M.D., M.Sc.; Ritu Agarwal, Ph.D., M.B.A., M.S.; and Ian Frank, M.D. 

Budget Update

The budget update covered the status of FY 2020. The NIH received a $2.6 billion boost in the final spending bill of FY 2020. A table of the breakdown by institute and center showed that NIAID received a 6.6 percent increase, but DAIDS had a limited increase of $16 million. Ending the HIV Epidemic activities within Health and Human Services, primarily at CDC, HRSA, and the Indian Health Service, did receive increases for FY 2020. In addition, NIH received additional support for the Centers for AIDS Research (CFARs). In coming years, NIH will be requesting additional funds to support activities beyond the CFARs.

The Institute has adopted the following financial plan: 14th percentile payline for R01s for established investigators; 18th percentile for R01s for new investigators; no adjustments to competing and noncompeting renewals; and competing research initiatives may be reduced by up to 10 percent. The estimated success rate for R01s is 22 to 24 percent for the year.

Report Card: The NIAID payline history and success rates between 2016 and 2019 were shown. The NIAID payline in 2019 was the highest in the last four years (14th percentile for established and 18th percentile for new investigators). The number of R01 applications strongly increased in 2019 from 2018 (509 versus 389). The success rates were 21 percent for R21 grants, 25 percent for R01 grants, and 38 percent for P01 grants. 

Questions:

Q1: How has the average size of an R01 changed?

A1: The average R01 has increased above the rate of inflation, but a number of investigators are still funded by modular grants with flat budget limits. That's an interesting area for the community to engage with the NIH. Letters from Committees would be welcome to help us with addressing this issue.

Q2: Any thoughts on why was there an increase in R01 applications from 389 to 509?

A2: We don’t know exactly. Perhaps it was a timing issue.

Q3: Do you have any data on which ones were first-time R01s, and any relationship to CFARs seed grants for K23 or K01?

A3: We do have data on which applications were first-time R01s; we can break down the specific data in more detail in the future. With the differential payline, the extra four points does pick up additional new investigators.

Comment: I think in a lot of places, the main stress point for investigators now is K to R transition where investigators are thinking about career change; I think it will be useful if we can get more information about that and think about how to decrease that pressure in any way we can.

A3 (cont.): I will break this down in more detail in terms of number of physician scientists undergoing K to R, number of true new investigators that are funded and number that were renewal R01s. I agree that will be useful.

Scientific and Programmatic Updates

Ending the HIV Epidemic (EHE) Initiative

NIH’s role in the EHE cross-agency initiative is in implementation science. NIAID will work with our federal agency partners and others to develop and evaluate evidence-based practices and effectiveness to achieve specific goals. There are four pillars for EHE efforts: diagnose, treat, prevent, and respond to reduce new infections by 75 percent within 5 years and within 10 years get to a 90 percent reduction. Several NIH working groups and EHE initiatives (with pillar subgroups) were listed; NIH members are primarily from NIAID, the NIH Office of AIDS Research (OAR) and the National Institutes of Mental Health. Several NIAID-specific initiatives are being considered focusing on multidisciplinary approaches to improve HIV health outcomes, systems approaches (“diagnose and prevent” and “diagnose and treat”) and epidemiology to end the HIV epidemic. Initiatives will be carried out in partnership with our federal partners, CDC, and HRSA.

HHS recently rolled out their Ready, Set, PrEP Program (https://www.getyourprep.com) with the goal to reduce the cost barrier associated with Pre-exposure prophylaxis (PrEP) medications across the nation. The program provides PrEP medications at no cost to individuals who qualify. The U.S. Preventive Services Task Force (USPSTF) has recommended PrEP for individuals at risk of HIV acquisition. Going forward, PrEP access will be expanded from a mail order process to an additional 21,000 retail pharmacies across the 50 states as well as the jurisdictions. This we hope will make a big difference in terms of uptake.

HIV/AIDS Clinical Trials Network Recompetition Updates

We completed the peer review and scores were released to applicants for the Network Leadership and Operations Centers, the Statistical and Data Management Centers, and the Laboratory Centers. The investigators are awaiting their summary statements.

The Clinical Trials Units applications arrived in November and we are in the process of setting up the review panels and scheduling the review meetings later this spring. All Network awards are scheduled for December 2020. We are on schedule and updates will be provided at future ARAC meetings.

SBIR Contract Topics

The SBIR set-aside by current law is 3.2 percent of the NIH budget and 0.45 percent for STTRs. Thus, approximately 3.65 percent of the NIH budget is designated specifically for the SBIR/STTR program. It was discussed how the use of these funds can be optimized to meet the NIAID and DAIDS mission. Concept clearance is requested for FY 2020 topics in the HHS, NIH, and CDC Small Business Innovation Research (SBIR) Program contract solicitation PHS 2020-1.

Two SBIR contract topics that were previously approved by ARAC will be re-issued. These were briefly discussed:

  1. Particle-Based Co-Delivery of HIV Immunogens as the Next-Generation Vaccines
  2. Sequence-Based Assays To Quantify the Replication-Competent HIV Reservoir

Two new SBIR contract topics were introduced for approval vote:

Topic 1: Point-of-Care HIV Viral Load and Drug Adherence Assays To Accelerate Ending the HIV Epidemic
This topic covers novel, low-cost, real-time point-of-care assays for HIV viral load, HIV drug resistance, and pharmacological adherence monitoring. Phase I activities should include the development of prototype assays that can detect HIV and drug in various matrices and determine assay feasibility. During phase II, the applicants should propose further improvements of the assays developed in phase I, establish validation studies including quality control, and refine the commercialization plan.

Ballot Voting Outcome
9 Approval
0 Approval with modification(s)
0 Deferral for further information
0 Disapproval

Topic 2: Therapeutic Targeting of Intracellular HIV Proteins or Nucleic Acids
This topic aims to develop therapeutics against HIV intracellular proteins, previously thought to be undruggable. Phase I activities should include feasibility studies for new strategies to target intracellular HIV proteins, including proof-of-concept studies. During phase II, the targeting strategies developed during phase I should be optimized, and IND-enabling studies should be performed.

Ballot Voting Outcome
9 Approval
0 Approval with modification(s)
0 Deferral for further information
0 Disapproval

ARAC members voted to approve the two new SBIR contract topics.

Office of AIDS Research Advisory Council (OARAC) Update

Richard Chaisson, M.D. 

Dr. Chaisson gave a brief summary of the 52nd OARAC meeting held on October 28, 2019. This included the Director’s report and various recent and upcoming outreach activities, briefings, and updates:

Dr. Goodenow presented the Director’s OAR report. Key FY 2019 accomplishments included submission of the FY 2020 Professional Judgment budget and the FY 2021 Congressional Judgment budget. The OAR had evaluated over 1,100 projects within the HIV Portfolio to ensure that they aligned with the NIH HIV/AIDS Research Priorities. OAR staff had participated in several domestic and international meetings and held two listening sessions; one with investigators associated with the CFAR at Johns Hopkins University and one in the community with AIDS Action Baltimore. The new FY 2021-2025 NIH Strategic Plan for HIV Research and other items moving forward in FY 2020 were outlined. 

Nora Volkow spoke about drug addiction and HIV and implementation science initiatives for the opioid use epidemic. 

Frederick Altice spoke about implementation science projects in key populations looking at improved access and implementation of proven modalities for treating and preventing HIV.

HHS HIV/AIDS Guidelines from the Treatment and Prevention working groups: OARAC members urged the Guidelines Committee to emphasize the importance of Undetectable = Untransmittable (U=U) message. There were updates on the guidelines for children, both for ARVs and OIs, and prevention of mother-to-child transmission in pregnant women. 

The strategic plan for FY 2021-2025 was summarized. The plan represents to shift to a five-year plan with periodic updates anticipated. 

David Wilson spoke about how the NIH is working with Native American communities to address their health and research needs. Of note: Urban Indians are also a population at high risk for HIV and viral hepatitis.

AIDS and Related Research (AARR) Integrated Review Group Reorganization: A report on how CSR AARR realigned study sections was provided. Three cycles of peer review (beginning January 2019 Council) demonstrated that the balance of reviews improved so that each study section is getting a reasonable number of grants to review and that the change has been fairly well received. 

Questions: None

AIDS Vaccine Research Subcommittee (AVRS) Update

Dale Hu, M.D., M.P.H.

Dr. Hu focused on specific highlights from the AVRS meeting, concentrating on the Division of AIDS Vaccine Clinical Research Branch. The major areas of this branch are to design and conduct clinical trials, to elicit and evaluate vaccine-induced immune responses, to look at social behavioral research in clinical research, and to actively coordinate the clinical research portfolio with internal and external partners. As of January 1, 2020, NIAID-supported 22 HIV vaccine trials covering 35 products and over 13,000 volunteers. Additionally, during the last three or four years there has been a dramatic increase in the number of efficacy trials which is unprecedented in HIV vaccine research. Graphical and tabular data were shown for the HVTN protocol timeline (2019-2023), current efficacy studies, HIV vaccine trials with adjuvants (ongoing or planned), and novel adjuvants in HVTN 137. The AMP study was briefly described with the exciting news that the projected last infusion will be mid-February 2020, with 98 percent adherence to the infusions. A cross-program/network collaborative sub-study of AMP (antiretroviral analytical treatment interruption) to assess the immunologic and virologic responses in participants due to begin in 2020 was outlined. Several early phase mAb studies were listed. These could be used next in combination and moved further into efficacy trials. Immunohistochemical data from one of these studies, HVTN 116, that looked at VRC01 in the AMP studies, showed that a single injection of VRC01 is detectable in rectal tissue for only the first six weeks, whereas the long-acting VRC01-LS version is detectable up to 52 weeks. It is anticipated that mAbs which target multiple sites will improve the prevention efficacy of regimens. There are many new immunogens and mAbs and currently there is a strong effort to streamline them to move the best ones into efficacy trials. Dr. Hu summarized the HVTN laboratory center activities that take place in over 100 laboratories on four continents, and the role of Behavioral and Social Sciences and their contributions at all phases of clinical research. Scientific priorities for the next five to seven years were listed highlighting a plan to expand into pediatric populations.

Questions:

Q1: Is there evidence that VRC01 could reduce the size of the reservoir prior to a treatment interruption? (ii) Are the placebo recipients who were infected also going to be included in the treatment interruption study?

A1: There have been several studies, both in nonhuman primates as well as some of the early human studies, that support VRC01 will be a good adjunct to possibly improve the immunological response. I can't go into all these in detail, but I think that there is good evidence that this is an interesting approach. (ii) Placebo recipients will be included because that is an important comparison. 

Q2: How many prevention trials are you planning, and how and who is going to decide which ones make it into the human trials?

A2: We have half a dozen studies; obviously they don't cover all the broadly neutralizing antibodies that are in the pipeline. I think that Dr. Marovich will talk about CHIP, which is a coordination effort with partners to prioritize candidates that move into trials.

Q3: Would you be able to provide a little more context and texture around the comment on the previous slide about expanding socio-behavioral work associated with clinical trials?

A3: The first goal is to integrate socio-behavioral research into trials to increase scientific understanding and adherence to the study visits. Initially, we plan to focus on existing trials. A second important area is how we look at adherence, and how we engage participants with the long-acting mAbs and other ART interventions. The third area focuses on the challenge in conducting HIV studies because of the reduced incidence since PrEP is increasingly prevalent. Also, there are issues about how PrEP might influence early HIV infection and the possibility of detecting early infection.

Programmatic Overview: Key Accomplishments and Future Directions

SBIR/STTR Program-Scientific Update of Funded Topics

Brigitte Sanders, DVM, Ph.D.

Dr. Sanders gave an overview of the NIAID and DAIDS SBIR and STTR Program and an update on the awards made for recent SBIR Contract Topics. NIAID participates in the R41, R42, R43, and R44 omnibus solicitations that do not allow for clinical trials and issued a unique U44 clinical trial funding opportunity announcement, PAR-18-632. High-priority areas for SBIR grants were listed and included the development of anti-HIV agents, therapeutic vaccines, and strategies for curing HIV infection. Two examples of DAIDS success stories were presented. (i) The first is from Navigen Pharmaceuticals from Salt Lake City who developed a gp41 targeted-specific D peptide, PIE12-Trimer. Their research studies showed that the PIE12-trimer, the lead candidate, is highly potent and that inhibits all major HIV clades. Navigen, with SBIR support, demonstrated antiviral activity in an explant model and in a rhesus SHIV model. They completed all IND-enabling studies and submitted an IND application. (ii) The second example involved Emmune from Juno Beach, Florida. The company’s scientists, with SBIR support, constructed multiple improved versions of the eCD4-Ig fusion proteins, improved the pharmacokinetics criteria and made modifications to reduce immunogenicity. 

Next, SBIR contracts and recent awards issued to various companies in 2019 were listed and briefly discussed. Specifically, awards to companies made under the topics ‘Particle-Based Delivery of HIV Env Immunogens, Methods Improving HIV Protein Expression: Cell Substrate and Protein Purification, In Vivo Targeted Degradation of HIV Proteins, Effective Targeted Delivery of RNA-based Vaccines and Therapeutics and Co-Delivery and Formulation of Adjuvants for HIV Vaccines’ were discussed.

Questions:

Q1: Some of the topics presented are incredibly important, but there may not be much of a commercial market. How much of a business plan is included in the applications?

A1: The only qualification needed is that the company has to be for-profit and employ not more than 500 employees. There are many companies in the epidemiological and social sciences field and also for assay development.

Q2: Are druggability and formulation criteria for funding these projects?

A2: In Phase 1, the applicants are supposed to demonstrate feasibility and druggability and formulation would be part of this. Phase II is commercialization and applicants are required to submit a commercialization plan, which shows that they can bring the drugs to the market.

Vaccine Research Program (VRP)

Mary Marovich, M.D.

Dr. Marovich’s talk focused on preclinical and translational topics and covered HIV-1 vaccine discovery, design advances, and future directions.

Broadly neutralizing antibodies (bNAbs): It is unknown if bNAbs protect humans and whether vaccines can elicit bNAbs. Multiple components for a vaccine are needed. The different approaches to elicit bNAbs were briefly described: lineage based, germline targeting, and epitope based. Design strategy-specific immunoassays/endpoints were outlined. It was stressed that approaches are consistent and coordinated, well-planned with the laboratory team, so there will not be any surprises, and good decisions can be made based on data. A list of HIV bNAb immunogens was shown that are either in GMP production or in Phase 1 testing. They were broken down by the germline-targeting, epitope-based or trimer approach. While there is major investment in these immunogens, coordination of production and testing is still needed and underway.

Candidate vaccine platforms were briefly described including: 

  • Louis Pickers’ CMV platform: This approach has reproducibly been shown to control a highly pathogenic SIV infection in vaccinated animals. Transcriptomics can be used to predict which animals will be protected when using these specific CMV vectors. 
  • Rama Amara’s novel vaccines: The investigators did comparison studies using an envelope trimer (SOSIP) only, which is a native trimer vaccination of primates, versus a heterologous viral vector priming followed by SOSIP trimer boosting. They found that using the heterologous vector prime and then boosting with the trimer resulted in a lowered threshold of neutralizing antibodies that were required for protection and increased durability of protection compared to vaccination with SOSIP trimer only.
  • Darrel Irvine’s slow delivery immunization strategies: He is using trimers to enhance HIV NAb and germinal center responses by recruiting more diverse B cell lineages, greater antibody diversity, and generating more memory B cells. Their studies with combination adjuvants were presented comparing the saponin-MPLA Nanoparticles (SMNP) adjuvant with other preclinical and clinical adjuvants. The SMNP adjuvant was superior. 

The need for access to adjuvants was addressed with VRP helping the larger NIAID working group in developing its strategic plan for research on vaccine adjuvants. The VRP HIV Env nanoparticle/mRNA portfolio in production or development was discussed. It was noted that many investigators are now moving towards the mRNA platform because it can accelerate the time to produce and decrease overall costs.

Other topics briefly addressed were:

  • Translating NHP data to humans: These studies focused on adjuvant comparisons using BG505 SOSIP in the HVTN137 trial. A parallel nonhuman primate study is planned.
  • CHIP (Collaborative HIV Immunogen Project). A major aspect of this portfolio is to use vaccines to develop bNAbs but need to find ways to coordinate the development of these immunogens, starting out with the NIAID-funded HIV Vaccine Consortia, like the CHAVDs and the Vaccine Research Center at the NIAID Campus, and begin by having these groups work closely together to share information and work efficiently.
  • Partnership strategy: An approach to leverage NIAID investments in vaccine development research. This aims to decrease trial costs, de-risk and incentivize industry and then to hand-off to a company that might be interested in further development or commercialization.
  • Pox Protein Public-Private Partnership (P5): This includes a research track comprising multiple Phase 1 studies in humans that compare delivery routes, looking at the bio-jector versus needle and syringe for DNA. Adjuvant comparisons have been done using AS01B and MF59, for example, versus alum here, and examined DNA priming and protein co-administration. Those studies are all enrolled and the participants are in follow-up. The data are currently being analyzed and manuscripts are being written.
  • Janssen collaboration: This public-private partnership with Janssen as the partner in 2013. Multiple studies have been jointly run through the HVTN Phase 1 and now a Phase 2B study, HVTN705. Now a Phase 3 study, HVTN706 is being carried out.

Questions:

Q1: What fraction of budget is being spent on clinical trials versus preclinical research development?

A1: We will get back to you on that to provide accurate information.

Q2: Who is making the decisions about what to take forward into clinical trials and how do you evaluate whether those decisions are the right ones?

A2: We are trying to improve on the ability of the human immune system to prevent acquisition and sufficiently fight off infection. For the broadly neutralizing immunogen program, there are viral targets that we believe are on steady ground. We talked about manufacturability and avoiding too much overlap and making sure you have multiple targets covered. There are minimal criteria that need to be met in order for an investigator to move something forward and those are becoming more and more stringent, for example evidence of manufacturability, evidence that you're signaling through B cells with calcium influx and evidence in small animal models for stimulation of precursor B cells. We are working together now through the CHIP to bring expertise together and assess what makes the most sense in a reasonable amount of time. New studies need to be small and focused. These experimental medicine studies with a small number of participants and no placebos can be streamlined to inform decisions for iterative vaccine design.

Comment: I'd guard against the rush to the clinic. We really don't know at this point how to elicit protective immune responses. Having a very strong and healthy preclinical research nonhuman primate program has been outlined nicely here; however, the temptation is that we have these broadly neutralizing antibodies that look like they work very nicely so let’s spend millions of dollars on showing that they're protective. We somewhat know that they're going to be [protective] if they're given in the right way. I'd just make a plea not to put too many eggs in the product development basket at the expense of the research basket.

Basic Sciences Program (BSP)

Diana Finzi, Ph.D.

The Basic Sciences Program covers a vast scientific landscape, from early basic science to generate new ideas to feed the pipeline to more applied research. This involves working with other programs: therapeutics, prevention, and vaccines. The BSP is composed of three branches: Pathogenesis, Targeted Interventions, and Epidemiology. 

An overview of the program was given, and highlights of initiatives were presented, including future directions. 

Over the past year, three major events have had a direct impact on BSP:

The first is the transfer of the HIV/AIDS portfolio from the NIH National Institute of General Medical Sciences (NIGMS) to the DAIDS BSP.

The second is the recently announced “Cure” collaboration with the Bill and Melinda Gates Foundation, which aims to cure both HIV and Sickle Cell Disease.

The third is the announcement by President Trump at the 2019 State of the Union address last February that we are going to end the HIV epidemic and eliminate new HIV infections in our nation. A team from multiple HHS Operating Divisions is collaborating on Ending the HIV Epidemic: A Plan for America.

Areas of focus/future opportunities include:

Structural biology portfolio ($52M, transferred from NIGMS)

  • Structural Biology Centers overview: These Centers support a significant number of investigators and they essentially serve as hubs for structural biology for HIV.
  • Each Center is focused on a particular aspect of the HIV life cycle. 
  • Accomplishments included supporting 132 investigators with 18 developmental grant awardees and collaborative development awards that have led to numerous spinoff R01s for young investigators.

BSP initiatives being considered for reissue include: Understanding HIV Rebound, Limited Interaction Targeted Epidemiology (LITE), Understanding HIV Reservoir Dynamics and New Technologies for the Delivery of Gene Therapeutics for an HIV Cure.

Future directions were expanded on:

Basic Science:

  • Strengthen and recompete the HIV Structural Biology Centers
  • Focus on basic biology of host-virus interactions and mechanisms of latency and persistence

Targeted Interventions:

  • Discover and translate non-traditional therapeutics such as gene- and cell-based therapies, biologics, and RNA therapeutics

Epidemiology:

  • Partner closely with other Institutes on outcomes of disease (including big data)
  • Increase understanding of transmissions and support studies towards EHE

Questions:

Q1: How do you publicize Structural Biology Centers so that investigators can think about collaborating with those Centers?

A1: They publicize themselves and do look for collaborations. We are considering having some portion of the funding go towards developmental projects and having people reach out to them to work together. As far as publicizing, I think it comes mostly from the investigators and the work they do and being known to the community.

Comment: Centers were mandated to spend about 10 percent of the budget on collaborative work. There is a defined process for outside investigators to bring their projects to the Structural Biology Centers for collaboration and it works very well.

Q2: CFAR implementation projects. What will be the mechanism to move forward with the most promising implementation projects?

A2: This year there was an internal competitive process. Perhaps, the CFARs need to issue a call for implementation projects.

Q3: Purpose of specific LITE program? How successful is that mechanism to identify individuals who are likely to seroconvert? Where does the program go?

A3: The previous LITE initiative was very successful, identifying around 350 seroconversions. We are interested in continuing the program with a strong focus on women.

Q4: In the first LITE study, do you have a sense of what proportion of your high-risk individuals are from minority populations?

A4: The cohorts were required to enroll more than 50 percent minority populations. 

Q5: What about inclusion of individuals who inject drugs?

A5: We need to look at this topic in collaboration with NIDA since it is more within their mission.

Comment: Targeting prevention strategies that we know work in other settings was discussed at the OARAC meeting by Dr. Volkow of NIDA; the digital tool of the LITE may not be the best approach for reaching populations with different risk characteristics. 

Q6: Can you comment about the inheritance from NIGMS, in particular the R01s because NIGMS has a different funding philosophy than NIAID—more generous pay lines, less generous budgets. How are you managing that for the cadre of investigators who are transferring to NIAID?

A6: We are determined to protect NIGMS funded HIV investigators as much as we can. The inclusion of the previously NIGMS applications in the NIAID pool will change the mix; we will have to watch this over time. 

Therapeutics Research Program (TRP)

Peter Kim, M.D.

The mission of the Therapeutics Research Program was outlined: improve the health of people living with HIV (PLWH) mainly by developing therapeutics, including long-acting antiretroviral regimens, diagnostics and associated strategies to achieve durable viral suppression, and ART-free remission in all people living with HIV. This program is geared towards clinical trials with the Basic Science Program, serving as our basic science counterpart. There are over 70 clinical trials that are active or in development. Most of the clinical trials are focused on HIV cure and HIV treatment, and a number are based on tuberculosis, hepatitis, inflammation, and end-organ disease. Resources and the infrastructure to support the quality of those clinical trials were outlined and it was noted that the TRP maintains a portfolio of clinical support contracts that ensure high quality of clinical trials. Clinical research supported by grants also serve as resources for the global research community. Two were described: the Stanford University HIV Drug-Resistance Database and the newer Long Acting/Extended Release Resource Program (LEAP), which has been instrumental in helping advance the field of long-acting therapeutics for HIV.

Funding opportunity announcements (FOAs) in FY 2019 were summarized and select clinical trials and advancements were described including:

HIV studies:

  • A combination of broadly neutralizing antibodies (bNAbs) was reported to have the potential to suppress viral replication in the absence of ART.
  • A publication showed that a single antibody can bind to multiple epitopes to affect a combinatorial approach. This showed that multiple antibodies may not need to be infused to get that combination effect, but possibly only encoding that sequence into a single antibody. For example, a singleVRC01 or PGDM1400 infusion, which are two bNAbs, did not perform as well as the combination of VRC01, PGDM1400, and 10E8 trispecific Ab. A Phase I clinical trial (A5377) with ACTG is now underway to evaluate this trispecific Ab in people with HIV.
  • Research to understand how HIV resistance to bNAbs evolves/emerges is needed to inform new clinical strategies for bNAb use.

Tuberculosis studies:

Tuberculosis (TB) is a major cause of morbidity with people living with HIV

  • Combining high dose rifapentine and clofazimine significantly shortened the time to sterilization in two mouse models of drug sensitive TB 
  • A5362: A Phase IIc Trial of Clofazimine- and Rifapentine-Containing Treatment Shortening Regimens in Drug-Susceptible Tuberculosis: The CLO-FAST Study
  • ACTG and IMPAACT for Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (PHOENIx MDR-TB) trial

Hepatitis studies:

  • cccDNA (covalently closed circular DNA) transcription is reduced in HIV/HBV coinfected people with longer antiviral duration
  • A5379: B-enhancement of HBV Vaccination in Persons Living With HIV (BEe-HIVe): Evaluation of HEPLISAV-B

Other comorbidities and coinfections:

The aim here is to collaborate with appropriate stakeholders and groups

  • Tesamorelin study: This multicenter TESLA trial is for non-alcoholic fatty liver disease (NAFLD) which is a substantial cause of comorbidity in people with HIV and there are no proven pharmacological treatments for the disease in this population.

Questions:

Q1: Can you talk about strategies to coordinate efforts with different groups?

A1: That strategy entails communication at multiple levels. We have multiple platforms for that communication. Another platform recently convened under Dr. Marovich's leadership is called the Product Governance Committee. Any product that is considered for manufacture by the Division of AIDS is discussed at the Product Governance Committee. We are also collaborating with the Vaccine Research Center on their products.

Public Comments:

None.

Future ARAC Meetings:

June 1, 2020
September 14, 2020
January 25, 2021
June 7, 2021
September 13, 2021

Adjournment

Drs. Freedberg and Dieffenbach thanked the ARAC and community members and DAIDS staff and adjourned the meeting at 3:50 p.m.

VI. Adjournment

The meeting of the Council adjourned at 3:50 p.m., on Monday, January 27, 2020.

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

-s-

Anthony S. Fauci, M.D.

Chair, National Advisory Allergy and Infectious Diseases Council

Director, National Institute of Allergy and Infectious Diseases

5/27/2020

Date

 
-s-

Matthew J. Fenton, Ph.D.

Executive Secretary

National Advisory Allergy and Infectious Diseases Council

Director, Division of Extramural Activities

National Institute of Allergy and Infectious Diseases

5/26/2020

Date

 

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

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