NIAID Council Minutes—June 1, 2020

The 195th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened virtually at 10:30 a.m. on Monday, June 1, 2020. Dr. Anthony S. Fauci, director, National Institute of Allergy and Infectious Diseases (NIAID) presided as chair.

In accordance with the provisions of Public Law 92-463, the meeting was open to the public from 10:30 a.m. to 11:45 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 10:30 a.m. and from 11:45 a.m. to 12:00 noon for review and consideration of individual grant applications. Notice of the meeting was published in the Federal Register.

Meeting Attendees

Member Group

Present

Absent

Council Members

  • Dr. Ritu Argawal
  • Dr. Michael Brenner
  • Mr. Elling Eidbo
  • Dr. Mark Feinberg
  • Dr. Ana Fernandez-Sesma
  • Dr. Monica Gandhi
  • Dr. Paul Goepfert
  • Dr. Harry Greenberg
  • Dr. Amita Gupta
  • Dr. Marc Jenkins
  • Dr. Stanley Lemon 
  • Dr. Robin Patel
  • Dr. Audrey Pettifor
  • Dr. Gwendalyn Randolph
  • Dr. Anuradha Ray 
  • Dr. Kenneth Stuart
  • Ms. Kay Whalen
 

Ex Officio Members

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

NIAID Senior Staff

  • Dr. Hugh Auchincloss
  • Dr. Carl Dieffenbach
  • Dr. Emily Erbelding
  • Dr. Matthew Fenton
  • Dr. John Mascola
  • 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. Guest Speaker—John R. Mascola, M.D., director, Vaccine Research Center
IV. Report of the Allergy, Immunology, and Transplantation Subcommittee—Daniel Rotrosen, M.D., director, DAIT
V. Report of the Microbiology and Infectious Diseases Subcommittee–Emily Erbelding, M.D., M.P.H., director, DMID
VI. Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)–Carl Dieffenbach, Ph.D., director, DAIDS
VII. Adjournment

I. Review of Grant Applications

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

Funding Actions: The Council reviewed 4,686 research and training applications with primary assignment to NIAID for a requested amount of $1,872,934,019 in first-year direct costs and recommended approval of 2,335 applications with $797,682,974 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 five new Council members: Dr. Monica Gandhi, professor of clinical medicine, Division of HIV, Infectious Diseases, and Global Medicine at the University of California, San Francisco; Dr. Paul Goepfert, professor, Division of Infectious Diseases, Department of Medicine at the University of Alabama, Birmingham; Dr. Harry Greenberg, associate dean for research and the Joseph D. Grant Endowed Professor of Medicine and Microbiology and Immunology at Stanford University; Dr. Audrey Pettifor, professor, Department of Epidemiology, Gillings School of Public Health at the University of North Carolina at Chapel Hill; and Dr. Kenneth Stuart, professor and principal investigator, Center for Global Infectious Disease Research at the Seattle Children's Research Institute.

Dr. Fauci noted that most NIH employees whose work can be done remotely have been teleworking full time since March 16, and NIAID has seen no change in the pace of actions to grants and contracts. He summarized the increase in the use of virtual collaboration tools and meetings, along with the different platforms being used. 

The NIH COVID-19 Scientific Interest Group launched a new online lecture series covering topics on various aspects of the COVID-19 pandemic.

Consideration of Minutes of Previous Meeting

Council considered the minutes of the January 27, 2020 meeting and concepts that had been presented and approved them as written.

Staff and Organizational Changes

In the Division of Extramural Activities, Dr. Andrea Wurster has been selected as the new director of the Office of Extramural Research Policy and Operations. 

In the Division of Allergy, Immunology, and Transplantation (DAIT), Susan Cooper has been named director of the Office of Program Planning, Operations, and Scientific Information. 

Tributes and Awards

In late April, an international team of investigators leading the PAmoja TuLinde Maisha (PALM) trial, many of them NIAID staffers, were awarded the Society for Clinical Trials’ prestigious David Sackett Trial of the Year Award for 2020. The PALM trial evaluated four investigational therapies for Ebola during the recent outbreak in the Democratic Republic of the Congo and identified two effective therapies that were immediately adopted in the field.

Meetings and Events

On January 29, the White House Coronavirus Task Force was established to coordinate and oversee the Trump Administration's efforts to monitor, prevent, contain, and mitigate the spread of COVID-19. Vice President Pence chairs the Task Force, and Dr. Deborah Birx is the response coordinator. The Task Force used press briefings from the White House to communicate updates, guidelines, and policy changes to the public.

Task Force members have also used other forums to communicate the latest COVID-19 scientific developments and guidance on mitigation. On March 15, Dr. Fauci discussed COVID-19 progress and priorities on all the major Sunday morning news shows. In an effort to reach younger audiences, NBA basketball great Steph Curry interviewed Dr. Fauci on Instagram on March 26, covering topics from the effectiveness of face masks to the rationale for social distancing and wearing face masks. 

On March 3, the President visited the Vaccine Research Center (VRC) to see firsthand the work being done on COVID-19. The visit began with a media briefing during which Dr. Fauci reviewed experiences over the last two decades responding to emerging and re-emerging infectious diseases. After the briefing, the President toured the VRC. 

On March 5, NIH Director Dr. Francis Collins, Dr. Fauci, and VRC Director Dr. John Mascola briefed Vice President Pence, presenting an overview of NIH, describing the origins of the VRC, and outlining efforts to develop a COVID-19 vaccine. 

On March 12, NIAID hosted an Australian delegation, which included Australian Foreign Minister Marise Payne, and provided an overview of NIAID COVID-19 research efforts and discussed opportunities for increased cooperation between NIH and Australia to fight the disease.

Budget Update

Dr. Fauci began by comparing the fiscal year (FY) 2020 enacted budget with the FY 2019 final budget. NIH received an overall increase of 6.4 percent. NIAID received a 6.0 percent increase, which included $50 million for Combating Antimicrobial Resistant Bacteria research 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 adjustments to noncompeting and competing grants. Competing research initiatives have been cut up to 10 percent from their planned budget level. Our estimated success rates for research project grants will be 22 to 24 percent.

On February 10, President Trump released his FY 2021 budget request, “A Budget for America’s Future,” which includes an overall decrease to NIH of 7.2 percent, or $3.0 billion below the FY 2020 enacted level. 

Three emergency supplemental spending bills passed into law in March and April provide NIH with more than $3.5 billion in additional funding for the COVID-19 pandemic and other coronaviruses. NIAID received approximately 40 percent, or $1.5 billion, of this funding, which is available until the end of FY 2024. 

Legislative Update

On March 4, Dr. Fauci accompanied Dr. Collins to testify before the House Labor-HHS Appropriations Subcommittee on the President’s FY 2021 budget for NIH. Dr. Fauci provided updates on NIAID research, including research on HIV and a universal influenza vaccine. 

From January to June, Dr. Fauci participated in 32 Congressional briefings to provide updates in real time on progress in developing and rigorously testing COVID-19 vaccines and therapeutics.

Dr. Fauci briefed members of the Congressional Black Caucus on April 13 and spoke to members of the Congressional Hispanic Caucus on April 30 to discuss the important issue of health disparities and outcomes with COVID-19.

On May 12, Dr. Fauci testified before the Senate Health, Labor, Education, and Pensions Committee on recent advances in NIAID-supported COVID-19 clinical trials. He updated the Committee on the Phase I trial of the mRNA-1273 vaccine candidate developed by the NIAID VRC in collaboration with Moderna, Inc., as well as clinical trials of remdesivir and other COVID-19 therapeutics.

Dr. Fauci thanked NIAID staff who have participated in many briefings and events on his behalf over the last three months. 

Other Information Items

Dr. Fauci began by paying tribute to Larry Kramer, who recently passed away. Larry was a firebrand activist and an accomplished playwright and author who put our feet to the fire to make sure we were addressing HIV in the proper context. In the 1980s, he was at first a great adversary, but as the years went by, he became an acquaintance and a friend.

In March, the Conference on Retroviruses and Opportunistic Infections was held virtually. It featured a special session on COVID-19 and a presentation by NIAID’s VRC team on an HIV antibody delivery by an adeno-associated virus 8.

Dr. Fauci reported some disappointing news on an experimental HIV vaccine regimen (HVTN 702) that proved ineffective in preventing HIV. He then presented results of a successful study comparing long-acting cabotegravir to Truvada. Cabotegravir was at least as good and maybe a little better than Truvada, which is an important advance in prophylaxis for HIV infection.

NIAID recently established the COVID Prevention Network, which combines the expertise from three ongoing DAIDS and DMID networks and their global partners and demonstrates our ability to leverage resources for other diseases and use them for an emerging disease like COVID-19. The networks will continue their priority projects in HIV while making a major contribution to COVID-19. 

Dr. Fauci gave an update on COVID-19, providing statistics on the number of cases and deaths both globally and in the United States. NIAID developed a Strategic Plan for COVID-19 Research with four components—improve fundamental, basic, research, and knowledge of the viral biology and pathogenesis; develop diagnostics and assays; characterize and test therapeutics; and develop safe and effective vaccines. 

He summarized research being done related to each of the four components of the Strategic Plan, available research resources, recent relevant publications, and programs and partnerships that have been established to accelerate COVID-19 vaccine and treatment options. 

III. Guest Speaker—John R. Mascola, M.D., director, Vaccine Research Center

Dr. John Mascola began by noting that VRC’s mission is to conduct research leading to the development of vaccines and antibody products to treat and prevent infectious diseases, from basic research through early-stage clinical trials. Over the years, VRC’s vaccine research efforts have focused on HIV, universal influenza, Ebola/Marburg, and other emerging pathogens such as Chikungunya and Zika.

He focused on three main areas of VRC’s COVID-19 response:

  1. Structure-based vaccine design
  2. Rapid development of an mRNA candidate vaccine and advancement into clinical trials
  3. Isolation and development of therapeutic antibodies

Dr. Mascola said the rapid response to SARS-CoV-2 was possible because of previous work done on SARS in 2002 and Middle Eastern respiratory syndrome in 2012. 

He spoke about the importance of using structural knowledge of the SARS-CoV-2 viral surface protein in designing highly immunogenic vaccines; VRC’s development of the investigational vaccine mRNA 1273 through collaborations with Moderna, Inc. and the Coalition for Epidemic Preparedness Innovations; and other COVID-19 vaccine candidates in various stages of development. 

Phase 1 studies of several COVID-19 monoclonal antibody products are moving forward to determine clinical uses, which include treating COVID-19 infection to prevent progression of disease and preventing infection. 

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

Dr. Rotrosen welcomed the subcommittee members to the 195th meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting. 

Dr. Rotrosen presented the following scientific and Division activities:

Staff and Organizational Changes

Susan Cooper, M.Sc., Ms. Cooper has been promoted to director of DAIT’s Office of Program Planning, Operations, and Scientific Information (OPPOSI). Since joining OPPOSI in 2005, she has worked on a wide range of strategic and program planning activities, communications, policy, division personnel actions, and management of DAIT financial resources. From 1997 to 2005, she worked at NCI in the Office of Cancer Genomics and the National Cancer Institute (NCI) Strategic Planning Office; and prior to that had many years in academia and industry. She graduated from the University of Glasgow (Scotland) with an undergraduate degree in Biochemistry, followed by a master’s degree in Steroid Endocrinology from the University of Leeds (England).

Kristy Kraemer, Ph.D., In January 2020, after 20 years of service to the Division, Dr. Kristy Kraemer retired from the position of chief, Clinical Sciences Section, Transplantation Branch. Dr. Kraemer made important contributions to NIAID extramural research in transplant immunobiology, especially with respect to the science and techniques of allo- and xenotransplantation research in the nonhuman primate (NHP) model. 

Julia Shaw, Ph.D., In April 2020, Dr. Julia Shaw was promoted to the position of chief of the Basic Sciences Section, Transplantation Branch. Dr. Shaw graduated summa cum laude from St. Louis University with a major in biology, and then received her doctorate in microbiology from the University of California, Davis. She was a post-doctoral fellow in the Vaccine Branch at NCI, where she worked on HIV vaccine development, including studies in the NHP model; and also at the Ecole National Veterinaire d’Alfort, where she did research on immunization using adenovirus vectors in a murine model. She has been a very valuable program officer in the Transplantation Branch since 2016, making important contributions to TB’s nonhuman primate research program.

Jeffrey S Rice, M.S., Ph.D., Dr. Rice joined the Autoimmunity and Mucosal Immunology Branch in January 2020, as a program officer in the Autoimmune and Primary Immunodeficiency Diseases Section. Dr. Rice completed graduate training in Immunology and Microbiology with Dr. Betty Diamond at Albert Einstein College of Medicine, and a postdoctoral fellowship with Dr. John Cambier at the National Jewish Health/University of Colorado Health Sciences, before moving to NIAID as a program officer in the Transplantation Branch. Dr. Rice brings a wealth of knowledge and expertise to his new position, including management of grants, cooperative agreements, and contracts, and expertise in the fields of immunology, immunogenetics, transplantation biology, and autoimmunity.

Melissa Walker, RN, BSN, Ms. Walker joined the Allergy, Asthma, and Airway Biology Branch on March 2, 2020, as a project manager/nurse consultant. She completed her Bachelor of Science in Nursing in 2001, at Florida State University in Tallahassee, Florida. She joined NIH as a clinical research nurse, graduating from the Oncology Nurse Internship Program in 2002. She then worked on a bone marrow transplant floor for several years at the NIH Clinical Center, followed by various nursing positions on the East Coast in emergency departments and medical-surgical nursing units. She returned to NIH in January 2006 to work in the intensive care unit. In November 2007, Ms. Walker joined NCI, first as a research nurse for the Surgical Oncology Branch, then transferring to the Thoracic Gastrointestinal Medical Branch in 2013, before accepting her new project manager role within NIAID. 

Thomas Winters, Ph.D., Dr. Winters joined the Radiation and Nuclear Countermeasures Program in February 2020, as a program officer. Most recently, he was a case manager in NIAID’s Office of Initiative Development, managing development teams for funding opportunity announcements and contract solicitations for NIAID extramural divisions. Prior to that time, Dr. Winters served as a scientific review officer at NCI. For 15 years he was the DNA Repair Section Leader of the Clinical Center Imaging Sciences Program Nuclear Medicine Section’s Radiopharmaceutical Development Laboratory, where his research focused on studying radiation damage to DNA and cellular responses. He earned his doctorate in medical microbiology and immunology from The Ohio State University College of Medicine, where he studied biochemistry and DNA repair in herpes simplex viruses.

Division Activities

Allergy, Asthma, and Airway Biology Branch

Systems Biology of Early Atopy Investigator Meeting (SUNBEAM). On January 30, 2020, NIAID and Rho, Inc., organized a meeting in Rockville, Maryland to have key investigators discuss the SUNBEAM study. This study will combine efforts from the NIAID-funded Consortium for Food Allergy Research (CoFAR), Inner City Asthma Consortium (ICAC), and Atopic Dermatitis Research Network (ADRN). This prospective cohort study will enroll ~2,500 pregnant women (at any stage of pregnancy), the offspring’s biological father, and the offspring. Offspring will be observed from birth to age three years. Investigators will study the role and interrelationships of established and novel clinical, environmental, biological, and genetic prenatal and early-life factors in the development of allergic diseases through age three years, with an emphasis on food allergy and atopic dermatitis. A systems biology approach will be used to identify mechanisms and biomarkers underlying the development of food allergy, atopic dermatitis, and their endotypes. Finally, this study will collect, process, and assay or store environmental and biological samples for current and future use in the study of allergic disease development. 

Basic Immunology Branch

B Cell Epitope and Mechanisms of Antibody Protection and Large-Scale T cell Immune Epitope Discovery Contract Initiation Meeting. On January 21 and 22, 2020, a joint contract meeting with DAIT and DMID was held in Rockville, Maryland. The meeting brought together the contractors for these two epitope discovery programs, DAIT and DMID staff involved in this program, and representatives from the Immune Epitope Database and Analysis Resource (IEDB), which houses the immune epitope data generated by the contractors. The purpose of these programs is to support highly interactive, multidisciplinary teams for large-scale discovery of T cell and B cell/antibody epitopes associated with infectious or autoimmune diseases, alloantigens or commensal organisms, and validate these epitopes regarding their role in immune protection or immune-mediated pathogenesis in humans. This meeting provided a venue for the project investigators to give an overview of their projects and to develop scientific collaborations with each other to foster program success.

Immunity in the Elderly Meeting. The kick-off meeting of the Immunity in the Elderly program was held on February 21, 2020, in Rockville, Maryland. NIAID and NIA jointly support a total of eleven projects in this program, with six projects funded by NIAID, and five projects funded by NIA. The NIAID-funded projects are from Stanford University, Western Michigan University, Jackson Laboratory, Vanderbilt University, and Yale University. The NIA-funded projects are from the Tufts University, University of Texas at Austin, resTORbio, Inc., Dartmouth College, and University of Washington. Investigators presented an overview of their programs, preliminary data, and future plans. The meeting provided a venue to facilitate an exchange of ideas and to start new collaborations amongst the investigators.

Human Immunology Project Consortium II (HIPC II) Annual Meeting. On February 26 and 27, 2020, the annual meeting of this renewed cooperative agreement research program was held in Bethesda, Maryland. The HIPC II program (http://www.immuneprofiling.org/) is composed of nine U19 cooperative agreement awardees and is designed to characterize molecular profiles of human immune responses to infection or vaccination using systems immunology approaches. All of the data generated by the HIPC investigators are being made available to the broader research community through ImmPort (http://www.immport.org) and ImmuneSpace (https://www.immunespace.org/), an engine for exploration and analysis of HIPC-generated datasets. In addition, HIPC investigators, led by the Yale HIPC team, have developed an Immune Signatures database to make HIPC-generated immune signatures accessible and comparable, and to identify common and unique immune signatures that predict responses to different vaccine types (http://hipc-dashboard.org). The HIPC II program is co-led by the Basic Immunology (BIB) and Allergy, Asthma and Airway Biology Branches (AAABB) within DAIT, NIAID, and co-funded by all three NIAID extramural divisions (DAIDS, DMID and DAIT), which also provide programmatic oversight.

Immunity at the Maternal-Fetal Interface Meeting. The kick-off meeting of the Immunity at the Maternal-Fetal Interface Program was held on May 15, 2020, as an online meeting. Eleven projects were awarded under this program. They included investigators from Wayne State University, University of Pittsburgh, University of California at San Francisco, RBHS-New Jersey Medical School, University of California Irvine, Seattle Children’s Hospital, University of Pennsylvania, Boston Children’s Hospital, Cincinnati Children’s Hospital, and University of Southern California. Proposed projects and data were presented; investigators were introduced and made connections for future collaborations.

Glycoscience and Immunology at the Crossroads of Biology Workshop. The workshop was held in partnership between NIAID and NIDCR on May 27 and 28, 2020, as an online virtual meeting. Topics covered during the workshop included glycan effects in microbe-host interactions, immune-mediated diseases, and immune cell recognition and function. It also included strategies for using available glycan tools and developing resources to understand glycans in immune regulatory circuits. Areas of interest include tissue-resident immunity, targeted delivery, and harnessing host control of disease outcome. The meeting concluded with a discussion of the gaps in knowledge, current challenges, available glycan tools and resources, and suggestions of tools that may be useful to meet the needs of the microbial, dental, and immunological communities.

Autoimmunity and Mucosal Immunology Branch

Cancer, Autoimmunity, and Immunology Meeting. On March 23 and 24, 2020, the third annual meeting on Cancer, Autoimmunity, and Immunology was held via virtual conference. The meeting was co-organized by the American Association for Cancer Research, National Cancer Institute (NCI), NIAID, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and National Institute of Diabetes and Digestive and Kidney Diseases. The major goals of the meeting were to 1) foster better understanding of immune-related adverse events which occur in cancer patients after treatment with checkpoint inhibitor immunotherapies, and how that might inform the study of autoimmune disease and 2) better understand how to treat and manage immune-related adverse event during and following cancer therapies. The meeting featured talks from many investigators working on various autoimmune diseases and cancer.

Development of Sample Sparing Assays for Monitoring Immune Responses. On April 2 and 3, 2020, a wrap-up meeting of investigators was held remotely via GoToMeeting videoconference. The investigators discussed their progress over the previous five years. Fourteen projects on a range of topics were presented, including technology developed at a biotech firm and technology at an academic center which is now moving to commercialization by a startup company. Serological, cellular, and molecular assays were successfully miniaturized or made high throughput by investigators in the fields of virology, allergy, organ transplantation, and autoimmunity. In addition to the publications emanating from the program, the methods developed are being uploaded to ImmPort to facilitate sharing more widely with the research community. The program is continuing with six awards for the next five years.

Primary Immune Deficiency Treatment Consortium Annual Scientific Workshop. On April 29, 2020, the Primary Immune Deficiency Treatment Consortium (PIDTC) convened a one-day virtual Annual Scientific Workshop. For the PIDTC natural history protocols in severe combined immune deficiency (SCID), chronic granulomatous disease (CGD) and Wiskott-Aldrich syndrome (WAS), which have collectively enrolled nearly 1,800 subjects, the teams reviewed progress to bring to completion the clean-up of datasets and preparation of manuscripts for publication. New natural history protocols in SCID, CGD, and Primary Immune Regulatory Disorders (PIRD), all anticipated for launch during 2020, were reviewed. Additional presentations included 1) the prospective treatment study, “Conditioning SCID Infants Diagnosed Early” (CSIDE, supported by a NIAID U01, PIs: Sung-Yun Pai, Boston Children’s Hospital, Harvard Medical School; and Michael Pulsipher, USC), which is currently enrolling; 2) four best abstracts from among those submitted by attendees; and 3) a pilot project supported by the PIDTC (PI: Fabien Touzot, University of Montreal, Canada) on the pathophysiology of inflammation in CGD. The Keynote Presentation, “COVID-19 and Primary Immune Deficiency”, was presented by Dr. Steven Holland, NIAID, on behalf of the Patient Advocacy Groups of the PIDTC. The PIDTC, now in its 11th year of U54 funding (PIs: Jennifer Puck, UCSF; and Donald Kohn, UCLA) is sponsored by NIAID and co-funded by Office of Rare Disease Research, NCATS.

Cooperative Study Group for Autoimmune Disease Prevention. On May 5, 2020, the annual meeting of the Cooperative Study Group for Autoimmune Disease Prevention (CSGADP) was held by Zoom videoconference. The mission of this program is to engage in scientific discovery that significantly advances knowledge for the prevention and regulation of autoimmune disease. During the meeting, the group’s principal investigators and their co-investigators presented recent highlights from their projects in type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. The group also heard and discussed reports from investigators who were awarded funding from the CSGADP for pilot studies related to autoimmune disease prevention. 

Radiation and Nuclear Countermeasures Program (RNCP)

Janssen/AFRRI TPOm Data Overview. On October 2, 2019, NIAID’s RNCP convened a meeting entitled “Janssen/AFRRI TPOm data overview.” The objective of the meeting was to 1) obtain an overview of the major studies on the thrombopoietin mimetic, TPOm, 2) provide an update on the key learnings from the pre/post-dose and delayed effect experiments, 3) discuss the strengths and significance of the findings, and 4) discuss the regulatory pathway for this medical countermeasure under the FDA Animal Rule. The meeting was attended by the Janssen group (regulatory, clinical, pharmacology, and modeling scientists), PIs, NIAID staff, regulatory members, CROs, and other government agencies with overlapping interest. Following the meeting, Janssen intended to develop a robust regulatory pathway based on the animal data generated by NIAID support.

65th Annual Radiation Research Society Meeting – RNCP Radiation Medical Countermeasures Symposium. On November 4, 2019, NIAID chaired a session at the annual meeting of the Radiation Research Society in San Diego, California. RNCP staff hand-selected the presentations that were showcased in the session through an abstract review process that began in March 2019, and worked with the presenters to ensure that that symposium was seamless and carried out on schedule. At this session, five RNCP-supported investigators presented data on advances in medical management, possible treatments for acute and delayed radiation injuries, and the relationship between the microbiome and radiation-induced damage.

2019 Annual Update Meeting for the Centers for Medical Countermeasures Against Radiation Consortium (CMCRC). On December 3 and 4, 2019, the CMCRC annual meeting was held in Rockville, Maryland. CMCRC investigators and their staff from the four awarded cooperative agreements (Columbia University, Duke University, UCLA, and the University of Pittsburgh Medical Center) provided an update on the progress that has been made in their Centers over the past year. The meeting provided an opportunity for exposure of the portfolio to other federal government agency staff that were in attendance (including NCI, BARDA, NASA, DoD and FDA), and fostered dialog and collaboration among the CMCRC investigators and program staff regarding future research and development directions. Also present were three members of the External Advisory Board, who provided their insight into the successes and needs of the program. 

Cellular Therapies for Treatment of Radiation Injuries (U01) RFA-AI-17-001 Annual Meeting. On December 13, 2019, NIAID hosted an annual meeting to discuss progress made on seven U01 five-year grants awarded in FY 2018. Awardee presentations focused on the development of cellular therapies as mitigators of acute radiation syndrome (ARS). Topics include pre-conditioning of mesenchymal stromal cells to enhance immune system recovery and to treat acute and delayed complications of radiation injury, such as hematopoietic and gastrointestinal ARS. In addition, awardees presented data on recently awarded supplements for collaborations between U01s within this portfolio.

NIAID/BARDA Medical Countermeasure (MCM) Portfolio Update Meeting. On Feb 26, 2020, members of the NIAID/RNCP met with program managers responsible for MCM development within the Biomedical Advanced Research and Development Authority (BARDA). The purpose of the meeting, requested by the HHS Assistant Secretary of Preparedness and Response to be held semi-annually, was to provide programmatic transparency and ensure that research at each sister agency continues to be aligned, with no overlap between the two programs. Specific discussions focused on scientific updates in each agency’s portfolios.

Annual U01 Radiation-Induced Vascular Injury Meeting. On March 31, 2020, NIAID/RNCP conducted the U01 Annual Investigator Meeting “Elucidation of mechanisms of radiation-induced endovascular injury and development of treatments/mitigators for radiation-induced endothelial cell and vascular dysfunction”. The objective of the meeting was to provide an update on the progress made in the respective U01 grants over the past fiscal year, exchange ideas for refining the research and to provide a framework for collaborations among the investigators. The meeting was attended by the PIs, NIAID staff, regulatory members, and other government agencies with overlapping interest. Following the meeting, several PIs submitted collaborative concepts for supplemental funding to meet the goals of the original request for applications (RFA).

Concepts Presented for Clearance

NIAID OD Presentations

Trans-NIAID Data Science (AI-DS) Program Presentation: 
Ishwar Chandramouliswaran, M.S., M.B.A.
Office of Data Science and Emerging Technologies 

Notice of Special Interest (NOSI): NIAID Priorities for Biomedical Knowledgebases & Repositories: The subcommittee endorsed and unanimously approved this initiative.

FY 2021 SBIR Contract Topic: Informatics Tools (Data Science Tools) for Infectious, Immune, and Allergic Research: The subcommittee endorsed and unanimously approved this initiative.

FY 2022 – NIAID OD Advisory Council Presentation Concept Clearances: The subcommittee endorsed and unanimously approved these initiatives.

  • Trans-NIAID Data Science Program: Early-Stage Development of Data Science Technologies for Infectious and Immune-Mediated Diseases
  • Trans-NIAID Data Science Program: Enhancement or Sustainment of Data Science Tools for Infectious and Immune-Mediated Diseases
  • Trans-NIAID Data Science Program: Exploratory Data Science Methods and Algorithm Development in Infectious and Immune-Mediated Diseases
  • Notice of Special Interest: Secondary Analysis of Existing Datasets for Advancing Infectious Disease Research

Division Advisory Council Presentation Concept Review

FY 2022 Research Concept Clearances

NIAID Division of Allergy, Immunology, and Transplantation: Regulatory Management Center (RMC) 

This initiative will (continue to) provide critical high-quality comprehensive clinical site monitoring services support for DAIT-sponsored (and/or funded) clinical trial programs.

The subcommittee endorsed and unanimously approved this initiative.

NIAID Division of Allergy, Immunology, and Transplantation Clinical Site Monitoring Center (CSMC) 

The RMC contract provides regulatory and good clinical practice compliance support to DAIT’s Office of Regulatory Affairs for clinical trials conducted under NIAID-funded networks or investigator-initiated awards.

The subcommittee endorsed and unanimously approved this initiative.

Immune Development in Early Life (U01, U19, Clinical Trial Not Allowed)

This initiative will support research to define the mechanisms for establishing and maintaining immunity in early life and throughout childhood (0 – 18 years of age), including the impact of infection with or vaccination against infectious diseases on immune ontogeny/function.

The subcommittee endorsed and unanimously approved this initiative.

Cohort Studies To Improve Our Understanding of Influenza Immunity, Vaccine Response and Effectiveness in Older Adults (>65) (U01, Clinical Trial Not Allowed) 

To support the use of longitudinal cohorts to develop greater understanding of important elements of influenza immunity, vaccine response and vaccine effectiveness in older adults (65 and older) who live independently in the community or in assisted living communities.

The subcommittee endorsed and unanimously approved this initiative.

Adjuvant Comparison and Characterization

The Adjuvant Comparison and Characterization initiative will enable the comparison of different adjuvants using the same antigen/vaccine; enable broad evaluation of adjuvants from the same or across adjuvant categories/classes; and provide a rich data resource of highly characterized adjuvants to the scientific community.

The subcommittee endorsed and unanimously approved this initiative.

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

Director’s Report

Dr. Emily Erbelding, director of the Division of Microbiology and Infectious Diseases (DMID), chaired the NIAID Microbiology and Infectious Diseases Council Subcommittee meeting on June 1, 2020. Dr. Erbelding welcomed two new members to the Subcommittee, Dr. Harry Greenberg, Associate Dean for Research and professor of medicine and microbiology and immunology at Stanford University School of Medicine, and Dr. Kenneth Stuart, professor in the Department of Pediatrics at the University of Washington (UW) School of Medicine and Seattle Children’s Research Institute. She also provided a DMID personnel update, recognizing new staff appointments made in the Division since the last Council meeting, including: Lisa Herrod, Office of the Director; Lesley Dupuy and Kaitlyn Morabito, Virology Branch; Catherine Luke, Respiratory Diseases Branch; Wiriya Rutvisuttinunt and Grace Tietz, Office of Genomics and Advanced Technologies; and Kien Nguyen, Sonia Gales, and Ping Chen, Office of Biodefense, Research Resources, and Translational Research (OBRRTR). She also noted that Mark Williams was recently appointed the Research Resources Section Chief in OBRRTR.

Following staff introductions, Dr. Erbelding reported on several recent DMID scientific activities since the group last convened: 

  • NIAID Workshop on Acute Flaccid Myelitis Preparedness: the workshop was held in February 2020 to establish research priorities for NIAID and discuss possible Institute efforts to catalyze the development of new countermeasures.
  • Phase II-B Randomized Clinical Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis: the study was conducted by the NIAID-supported Sexually Transmitted Infections Clinical Trials Group and showed that volunteers who received LACTIN-V had significantly fewer recurrences of BV than volunteers who received placebo; the results were published in the New England Journal of Medicine.
  • Coronavirus Disease 2019 (COVID-19) Update:
    • Vaccines: Dr. Erbelding presented an overview of U.S. government-supported vaccine research efforts, noting the developmental status of several leading candidates. She also described "Operation Warp Speed," a new initiative by the White House designed to accelerate the development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics. A number of U.S. government agencies have come together for this massive undertaking, with NIAID assuming a significant role in this effort. She also noted that NIAID extramural and intramural partners have formed the COVID-19 Prevention Trials Network in order to bring together large clinical trial networks supported by NIAID to serve as the organizational structure for U.S. government-sponsored trials of COVID-19 vaccines.
    • Therapeutics: Dr. Erbelding provided additional information on the NIAID-supported Adaptive COVID-19 Treatment Trial, which in its first iteration compared remdesivir to standard-of-care alone. Preliminary results were recently published in New England Journal of Medicine and showed that hospitalized patients with advanced COVID-19 and lung involvement who received remdesivir recovered faster than similar patients who received placebo. She reported that the next iteration of this adaptive trial would focus on adding an anti-inflammatory agent, baricitinib, to the remdesivir regimen.
    • Resources: Dr. Erbelding reported that the reagents from the NIAID-supported BEI Resources Repository, the Centers of Excellence for Influenza Research and Surveillance (CEIRS) and the World Reference Center for Emerging Viruses and Arboviruses have been critical for the development of molecular tests to detect SARS-CoV-2 virus as well as serology tests to detect antibodies against the SARS-CoV-2 virus. She noted that the CEIRS network of investigators have pivoted to COVID-19 and have generously made viral isolates and other reagents available to the research community.
    • Serology: Dr. Erbelding reported that NIAID organized an HHS-wide serology workshop, organized by Dr. Cristina Cassetti, deputy director of DMID, in May focused on: reviewing ongoing COVID-19 serosurvey studies; reviewing current knowledge on serological assay performance; and identifying gaps and outstanding issues to detect SARS-CoV-2 seroconversion in humans.

Concepts Presented for Clearance 

The following FY 2022 concepts were presented to the Subcommittee:

A Multidisciplinary Approach To Study Vaccine-Elicited Immunity and Vaccine Efficacy Against Malaria–the objective of this concept is to support research to characterize baseline immunologic status and malaria vaccine-elicited immunity to Plasmodium parasites, to identify the underlying mechanism(s) of vaccine-elicited immune protection or factors that contribute to changes in disease risk, and further dissect those factors that influence baseline immunity or vaccine-elicited immunity in malaria endemic regions. The Subcommittee members were supportive of the proposed initiative and considered it to be a timely, much needed, and high priority research topic. They recognized the opportunity to build on data and samples from completed or planned malaria clinical trials/studies or immunization programs. The Subcommittee members appreciated the complexity of the malaria vaccinology issues as well as the importance of engaging other research communities. Furthermore, the Subcommittee members acknowledged the need to incorporate modern technologies to leverage high-throughput systems-type datasets and conduct integrated and comprehensive analyses to address low vaccine efficacy and host hypo-responsiveness issues observed in field settings. Subcommittee members recommended building connections with existing NIAID programs and resources such as the Human Immunology Project Consortium network and International Centers of Excellence for Malaria Research, in order to leverage ongoing research activities and established data repositories and analytical tools. It was also noted that the issue of host hypo-responsiveness to vaccination may have broader implications for vaccination against other global diseases in endemic regions. Consideration of novel scientific approaches, such as available monoclonal antibodies, to help focus investigation of appropriate host signatures was also suggested. The concept was unanimously approved.

Tropical Medicine Research Centers (U01)–the objective of this concept is to support multidisciplinary research at Tropical Medicine Research Centers on the epidemiology, pathogenesis, diagnosis, treatment, and prevention of Neglected Tropical Diseases in endemic areas, and build in-country research capacity. The Subcommittee members strongly supported renewal of the Tropical Medicine Research Centers (TMRC) program to conduct research on Neglected Tropical Diseases (NTDs) in endemic settings. The scientific productivity of the TMRC to date was appreciated, and members endorsed the multidisciplinary approach and proposed alignment with the WHO’s “Roadmap on NTDs for 2021-2030.” Subcommittee members recognized that the TMRCs provide a unique opportunity for training United States and international researchers in tropical medicine research and funding pilot projects submitted by early-stage investigators. Furthermore, recognizing that there are numerous NTDs posing many different research challenges and opportunities, Subcommittee members recommended, and staff agreed, that research on a broad spectrum of NTDs should be supported. A Subcommittee member was concerned about the potential impact of expanding the eligibility criteria in the proposed initiative to allow applicants from the United States, thinking that this might conflict with the overall goal of building capacity within endemic countries. Staff suggested that this should not be a major issue since the applicants would need to commit 70-75 percent of the research funding to endemic sites. The concept was unanimously approved.

Coccidioidomycosis Collaborative Research Centers (U19)–the objective of this concept is to establish collaborative research centers to conduct multidisciplinary research focused on a unifying theme to improve understanding and treatment of coccidioidomycosis (Valley fever). The Subcommittee members were supportive of the concept to establish the Coccidioidomycosis Collaborative Research Centers (CCRC) and considered the concept timely and an excellent investment. They indicated that research centers incorporating collaborative, multidisciplinary projects, including supportive cores, were an appropriate mechanism to advance the field. The Subcommittee members acknowledged that Valley fever is a serious infectious disease that presents in many ways, including meningitis and bone infections, and that this concept would provide an opportunity to improve the diagnosis, treatment, and prevention of coccidioidomycosis (Valley fever). Some members asked if other dimorphic fungal pathogens would be included, as they can overlap diagnostically. Staff suggested that the discoveries made through the CCRCs have the potential to positively impact treatment and understanding of these other dimorphic species. The concept was unanimously approved.

Understanding the Role of the M. Tuberculosis Granuloma in Tuberculosis (TB) Disease and Treatment Outcomes–the objective of this concept is to support in-depth analyses to understand the role of M. tuberculosis (Mtb) granulomas in TB disease and treatment outcomes. The Subcommittee members were supportive of a funding opportunity to solicit research projects to understand the role of the M. tuberculosis granuloma in TB disease and treatment outcomes. A Subcommittee member noted that this concept has a clear focus and could be complementary to a related NIAID research program, the Tuberculosis Research Units Network. Another Subcommittee member noted that this was an exciting and important concept that would address our current lack of knowledge on the TB granuloma. Subcommittee members noted that focusing on the lung granuloma versus granulomas in any part of the body is appropriate, given that the lung is the most likely location for relapse and transmission. A Subcommittee member also noted that these studies would provide knowledge about TB granulomas in any part of the body, as well as granulomas that form in response to other diseases. Subcommittee members agreed that any studies on the role of the microbiome on the TB granuloma should be focused on the lung or pulmonary microbiome. Finally, a subcommittee member emphasized the need for NIAID to continue to be a leader in TB research, since TB is the lead infectious disease killer world-wide. The concept was unanimously approved.

Tuberculosis Research Advancement Centers (TRACs) (P30)–the objective of this concept is to enhance multidisciplinary collaboration across all aspects of TB research and help develop the next generation of scientific leaders in TB research. Recognizing that TB is the leading infectious cause of death worldwide, the Subcommittee members expressed strong support for this concept, which will establish Tuberculosis Research Advancement Centers (TRACs) to advance TB research at U.S. institutions. There was overall support for the P30 funding mechanism and for allowing multi-institutional TRAC applications. Subcommittee members had specific questions related to eligibility. Program staff clarified that multi-institutional applications from geographically distinct locations would be allowed, but applicants would need to clearly demonstrate how users would access core resources if not co-located. Since experience from other programs suggests that there is less value in supporting individual institutions lacking a critical mass of researchers, Program staff suggested that institutions with few or no TB investigators could collaborate with other institutions to submit multi-institutional applications. The Subcommittee members acknowledged NIAID’s contributions to global TB research. The TRACs concept was unanimously approved.

Understanding Evolutionary Dynamics of Influenza To Inform and Improve Vaccine Strain Selection (R01)–the objective of this concept is to support studies of seasonal influenza evolution to accurately predict evolutionary trajectories of circulating influenza viruses and improve strain selection for the seasonal influenza vaccine. The Subcommittee members expressed strong support for the concept "Understanding Evolutionary Dynamics of Influenza To Inform and Improve Vaccine Strain Selection," noting the need for a better understanding of viral emergence and spread in light of the COVID-19 pandemic and the renewed interest in phylogenetic studies it has sparked. The Subcommittee members recommended expanding the scope regarding within-host evolutionary studies to include T-cell response and immunological pressure to internal epitopes, since much of the current focus is on B-cell response. Program clarified that the intent of this concept is to fund a diverse set of projects that will address basic evolutionary questions as well as the development of tools and modeling platforms to predict the next dominant strain. 

Furthermore, Subcommittee members and program also agreed that data sharing will be critical to the success of the proposed initiative and that investigators will be encouraged to connect with other NIAID programs and deposit data in NIAID supported- and/or other public repositories. Discussion centered on the long-term utility of investments in predictive computational tools. Some Subcommittee members suggested that directly funding the development of new manufacturing platforms might be more effective in improving influenza vaccines, while others pointed out the future potential of a universal influenza vaccine that covers more strains of influenza and limits viral emergence. Subcommittee members agreed with program’s assessment that knowledge gleaned from this concept will be valuable regardless of the availability of a universal influenza vaccine, especially given the time needed for its development and deployment. In addition, given the substantial investment that would be needed to scale up any newly developed manufacturing platform and the massive coordination necessary to implement its widespread adoption, this concept was viewed as a strategic investment towards an alternate solution. The concept was unanimously approved.

In closing, the Subcommittee members noted that several of the proposed concepts would benefit from increased budgets, should additional funding become available.

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

Dr. Freedberg welcomed everyone and the ARAC members approved the minutes of the January 27, 2020 meeting.

Director’s Report

Carl Dieffenbach, Ph.D.

Dr. Dieffenbach recognized the recent passing of activist Larry Kramer. New Committee members were introduced and welcomed: Dr. Audrey Pettifor, Dr. Monica Gandhi, Dr. Paul Goepfert, as well as Dr. Tricia Burdo as the new Office of AIDS Research Advisory Council (OARAC) liaison to the ARAC. Dr. Dieffenbach mentioned the recent promotions within the Division of AIDS (DAIDS): Dr. Jim Lane is now the deputy director of the Vaccine Research Program (VRP) of DAIDS, and Dr. Cesar Boggiano has been selected as chief of the Preclinical Research and Development Branch within the VRP.

Budget Update

The budget passed by Congress for the fiscal year (FY) 2020 was summarized and a key point was that NIAID received a 6 percent increase. While the NIH overall budget received a significant increase, the growth for HIV/AIDS was essentially flat, and for NIAID the Institute increase was 1.3 percent. For the NIAID FY 2020 financial management plan: the R01 payline for established principal investigators (PIs) is the 14 percentile and the R01 payline for new PIs is the 18 percentile. There were no adjustments to awards for noncompeting and competing grants. Up to 10 percent was shaved from competing research initiatives, and the application success rates are estimated to be in the 22 to 24 percent range. In the FY 2021 President’s budget request released on February 10, 2020, there were major and substantive budget cuts proposed across the NIH. Since the February release of the budget, we have experienced the coronavirus pandemic. The NIH subsequently received SARS-CoV-2 supplemental funding of approximately $3.6 billion, of which NIAID received about $1.5 billion in supplemental funding for various COVID-related purposes including basic research, pathogenesis, animal models, epidemiology, diagnostics, vaccines, and therapeutics. These funds are shared across NIAID to drive the Institute’s research agenda on coronavirus. 

Scientific and Programmatic Updates

COVID-19 Research Supported by DAIDS

A snapshot of some of the coronavirus research currently being supported by DAIDS was presented. This covered the following trials:

  • ACTG 5395 (a randomized, double blind, placebo-controlled trial to evaluate the efficacy of hydroxychloroquine and azithromycin) 
  • HPTN 405/HPTN 1901 (Characterizing SARS-CoV-2-specific immunity in convalescent individuals) 
  • HVTN 406/HPTN 1902 (Prospective study of acute immune responses to SARS-CoV-2 infection) in review
  • University of Washington (UW), Fred Hutchinson, and UC San Diego Center for AIDS Research (CFAR) epidemiological study looking at 35,000 people living with HIV and COVID-19

NIH is participating with Moderna in performing the trial of their vaccine which is slated to start soon. We believe it's important to gain experience with the technologies around coronavirus at our clinical research sites and get that up and going for the vaccine studies.

The epidemiological study at UW, Fred Hutchinson, and the UC San Diego CFAR has just begun and there are no data to report yet.

Coronavirus Prevention Network (CoVPN)

NIAID has created a new structure combining activities in two divisions, the Division of Microbiology and Infectious Diseases (DMID) and DAIDS, to bring together our clinical trials networks in order to serve as a focal point for U.S. government-sponsored trials on coronavirus vaccines and monoclonal antibodies (mAbs) for preventing acquisition of SARS-CoV-2. These trials will be prioritized within the networks and will be moved forward in an integrated way with the HVTN, HPTN, and the trials network in DMID - the Infectious Disease Clinical Research Consortium. 

The CoVPN structure was outlined and highlighted the five platforms or candidate COVID-19 vaccines. What is referred to as different vaccines or antibodies are considered the platforms. The intention is to perform harmonized efficacy trials of these candidates using the collaborating NIH Clinical Trials Networks. 

The vaccine trial using the mRNA1273 vaccine made in a collaboration between Moderna and the NIAID Vaccine Research Center is completely enrolled for Phase I. 

In terms of the antibodies that we're looking at, a number of companies have identified monoclonal antibodies that in a variety of systems appear to be effective in neutralizing SARS-CoV-2. The leading SARS-CoV-2 monoclonal antibodies, the companies, and current first-in-human trial timeframe statuses for integration into the network structure were noted. 

Ending the HIV Epidemic (EHE): A Plan for America

EHE supplement opportunities and applications were briefly reviewed and planned activities, meetings and conferences were listed. 

The updated NIAID HIV/AIDS Clinical Trials Network (CTU) recompetition timeline and status was presented. We are on track to make all Network and CTU awards in December 2020. 

HPTN 083 

Recently, good news was reported from this phase 2b/3 double-blind, safety and efficacy study of long-acting injectable cabotegravir (CAB-LA) compared to daily oral PrEP. The results obtained met the stopping rules for non-inferiority and the trial was stopped at the first data and safety monitoring board (DSMB) review. Results demonstrated that CAB-LA is highly effective for prevention of HIV acquisition in cisgender MSM and transgender women. DSMB recommendations for the study follow-up includes that all study participants are to be unblinded and to continue in the study to achieve more safety data. Participants in the oral PrEP arm are to be offered CAB-LA when it is available and those in the CAB-LA arm will continue to receive it or have the option to take oral PrEP instead. 

Discussion:

Q: Do you have any comments on HPTN 084?
A: This is a study being performed in women in sub-Saharan Africa. There was a pause in the study based on the findings of dolutegravir, so we are 6 to 12 months behind schedule. The trial is currently waiting for DSMB analysis. The NIH and ViiV Healthcare are committed to completing and obtaining an answer on HPTN 084, and there is an ultimate goal of filing documents with the U.S. FDA and others for approval of an injectable prevention strategy for both men and women. We are ensuring that sites are appropriately equipped with PPE and will be in keeping with each countries’ local and national guidance. The HPTN 084 study remains a major point of emphasis for DAIDS.

A slide with the dates of future meetings was shared:

  • September 14, 2020 (ARAC)
  • January 25, 2021 (ARAC)
  • January 26 and 27, 2021 (AVRS)
  • June 7, 2021 (ARAC)
  • June 8 and 9, 2021 (SWG)
  • September 13, 2021 (ARAC)

Concepts Presented for Approval

Prevention Sciences Program

Scaling up PrEP and STI Services To End HIV in the United States
David Burns. M.D., M.P.H.

The objective of this new biphasic initiative is to solicit and support research that will lead to effective strategies that contribute toward reducing HIV incidence by scaling up PrEP in sexually transmitted infection (STI) service settings. The 2019 presidential initiative, Ending the HIV Epidemic (EHE): A Plan for America, set two challenging goals - to reduce new HIV infections by 75 percent by 2025 and 90 percent by 2030. The EHE plan identifies four pillars that are key to ending the HIV epidemic in the United States: diagnose, treat, prevent, and respond. To achieve these goals, implementation science research is needed to optimize HIV treatment and prevention programs, and to strategically interrupt the expansion of HIV transmission networks. This concept is needed because while multiple HIV prevention interventions have been shown to have efficacy in clinical trials, evidence that they can have an impact at the population level is weak or lacking. Additionally, multiple population level universal test and treat trials have shown that “treatment as prevention” alone will not end the HIV epidemic. In the absence of antiretroviral therapy (ART), STIs increase the risk of transmitting HIV, and in the absence of PrEP, STIs increase the risk of acquiring HIV. Previously, it has been reported that “STIs serve as a critical surrogate for the need for PrEP (Cohen et al. JIAS 2019).” People seeking STI care who are at increased risk of HIV infection should receive HIV testing and be provided same-day ART or PrEP in an HIV “status neutral” manner that reduces stigma and increases uptake. Thus, projects funded under this initiative would be required to:

  • Develop cost-effective, status neutral strategies for providing HIV testing, ART, or PrEP to people seeking STI services in one or more of the 57 priority jurisdictions identified by the EHE Plan.
  • Devise pilot studies with national, state, and local implementers to rapidly scale-up these services in STI care settings.

These objectives were proposed to be best achieved using the R61/R33 mechanism. Applicants would be required to provide milestones in their applications which would be finalized and incorporated into the Notice of Award, then carefully reviewed as progress reports are received. The ARAC reviewers strongly supported the concept and their comments and recommendations were reviewed, summarized, and addressed.

Discussion: None

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

Basic Sciences Program

Detection of HIV for Self-Testing
Diane Lawrence, Ph.D. 

The purpose of this initiative is to support basic and translational research to develop innovative diagnostic technologies that will enable HIV self-testing during the earliest phases of acute infection or during viral rebound. Antiretroviral treatment is recommended as early as possible after HIV infection, but many infected individuals worldwide are unaware of their infection and have limited access to testing. There is evidence that Undetectable = Untransmittable (U = U), but only if viral suppression is maintained, and viral rebound is unpredictable and rapid following treatment interruption or development of resistance mutations. Current HIV self-tests depend on detection of host antibody responses several weeks after infection. But this misses initial peak viremia when transmission risk is high and cannot detect viral rebound following treatment interruption or emergence of drug resistance. Therefore, additional self-testing tools to detect HIV would enable individuals to more easily monitor their infection or viral suppression status. Several reasons for the need for this initiative included increased worldwide acceptance of HIV self-testing, a growing interest in monitoring of personal health measures, a need to reach individuals who might not otherwise test or have access to testing facilities, and recent advances in molecular diagnostics technology such as smartphone-enabled diagnostics. The objective of this initiative is to stimulate collaborative basic research partnerships to develop early-stage diagnostic technology strategies feasible as a self-test for simple, sensitive HIV detection. The emphasis will be on innovation and exploratory basic research, not product development. The ultimate goal is the development of an assay that provides sensitive HIV detection at the earliest possible time post-infection, or upon rebound. Key features sought in a future self-test were simplicity, low cost, ease of use with either blood or another biospecimen, and ease of repeat testing. Outcomes from PAR-17-471 were listed and the purpose of the reissue was briefly summarized. The ARAC reviewers recommended approval of this initiative and their comments were addressed.

Discussion: None

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

Limited Interaction Targeted Epidemiology (LITE-2) To Advance HIV Prevention
Gerald Sharp, Dr.PH.

The purpose of this initiative is to support research to help prevent HIV in the United States by creating and following extremely large cohorts of high-risk HIV-negatives and developing prevention interventions. This is a renewal of the original LITE-1 FOA, now in its third year, which expires in 2022. CDC data from 2010 to 2018 shows a 16 percent decline in HIV diagnoses for women over that time but no decline for men. The incidence among black men who have sex with men (MSM) was constant over this time period while rates for Latino MSM increased 23 percent, and rates for white MSM declined 26 percent. In 2018, MSM accounted for 67 percent of incident HIV cases in the United States, and blacks and Latinos accounted for 68 percent of cases among MSM. Therefore, to reach the goals for EHE, there must be a focus on black and Latino MSM, particularly those under age 55 years and especially those aged 25 to 34. The EHE program focuses on reducing HIV incidence in the 50 jurisdictions and the 7 largely rural states, but that focus excludes about 42 percent of the annual HIV infections in the United States. While it is feasible to address HIV in the 50 mostly urban jurisdictions with clinic or community-based studies, it is more challenging to do this in the more sparsely populated areas of the 7 primarily rural states and in the 1,500 other counties in the United States. Thus, ways to engage these at-risk populations remotely are needed. The LITE-1 studies showed that it is possible to inexpensively and rapidly enroll thousands of HIV-negative, minority MSM using digital methods and home-based HIV testing. LITE-1 investigators were able to target HIV hotspots in both rural and urban areas of the United States and to enroll MSM across genders, ages, and different races and ethnicities. Several LITE-1 based papers were listed and the continued challenge of finding MSM and transgender persons at risk was discussed as well as the advantages of electronically based cohort studies. While electronic enrollment is inexpensive and scalable, it is not free. Remote HIV testing is feasible by different approaches such as mailed saliva or DBS samples and self-testing with photographs of test results. The LITE-2 program goal is to enroll large, LITE cohorts of HIV-negative MSM and transgender persons in the United States representing those at highest risk for HIV in 2022 and forward. LITE-1 did not allow clinical trials, but LITE-2 will allow optional low-risk, digital clinical trials to allow investigators to develop and compare possible behavioral interventions to reduce HIV incidence. This FOA is a milestone-driven, two-phase process and it was emphasized that these are to be digital behavioral trials, not drug or IND trials, that need to be scalable if successful. The scope of research topics was listed. The ARAC reviewers’ comments were discussed and addressed. 

Discussion:

Q: The first iteration of LITE was open for women, but no sites applied to do HIV prevention in women through this sort of limited interaction approach.
A: One problem is that this initiative requires an HIV incidence outcome, so you need to have a study population with a fairly high incidence of HIV for it to be successful. There were no applicants to LITE-1 who proposed research focused on women, I believe because of the difficulty of trying to enroll enough women at high enough HIV risk who could be followed using these electronic methods. LITE-1 investigators were able to include a large number of men who have sex with both men and women, and it is expected that LITE-2 will also include such MSM. Reductions in HIV infections in this group should lead to fewer infections among women. A specific initiative that focuses on women is being proposed in the discussion that will follow.

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

Assessing Women at Risk: Epidemiology To End the HIV Epidemic (AWARE)
Joana Roe

The purpose of this initiative is to use a combined approach of qualitative data collection, as well as quantitative data sources and analytic methods, to identify and enroll women living in the United States. The primary goal is to assess the multifactorial processes and barriers that contribute to persistence of new diagnoses of HIV in this key population. Focused efforts are needed to provide meaningful, significant clues to the susceptibility and prevention of HIV in women. This program will allow NIAID to address a gap in knowledge on how best to identify and mitigate risks for HIV in women. Preliminary 2018 data show that women represent about 19 percent of the U.S. epidemic, which although continue to demonstrate a slight decline, new infections persist in some racial and ethnic subgroups of women. Various risk factors for women were discussed, including syndemic factors such as discrimination and stigma, the sexual network’s risk level involving partner status, and individual knowledge and use of prevention tools such as condoms and PrEP. The highest-priority questions that AWARE could address are which women to engage with current prevention approaches; what prevention information reaches women and whether it is sufficient to help women assess risk; and what actions can be taken? The scope of this initiative would include discovery of the most important contextual and modifiable risk factors that inform evidence-based HIV prevention strategies and services for women at the individual, community, or structural level. In addition, the use of diverse sources and methods for data collection, as well as robust statistical and modeling techniques harnessing data science, will be required. The required use of data science was discussed, specifically highlighting the possibility for a multitude of potential questions with full contextual information (where accessible). As HIV infection in women is a rarer event in the United States than in men, it is recognized that data collection requires larger sampling and variety. A few large cohorts and population studies across health and disease conditions were mentioned as examples of successful NIH research endeavors focusing on issues unique to women. AWARE would complement ongoing NIAID studies that are assessing risk for HIV while advancing data science. This initiative would help address NIH Office of AIDS Research high priorities for HIV research in several areas. Requirements for AWARE awards include feasibility, enrollment of women and adolescents in large numbers, and cultural appropriateness. Guidelines for nonresponsive applications were also listed. ARAC reviewer comments and suggestions were summarized, as well as responses to them. 

Discussion

Q1: Any thoughts, as with some of the other initiatives, on bringing the awardees together? Given the limited budget, are there opportunities for synergies?
A1: We can definitely look for ways to include that language in the funding opportunity announcement (FOA) and ensure funding to support such interactions.

Q2: Was there any consideration of including any exploration of spirituality and religious beliefs that women may have that may impact, mitigate risks for women?
A2: Yes, we don't imagine anything being excluded. I believe it is important to assess all the multifactorial contributors.

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

Centers for HIV Structural Biology
David McDonald, Ph.D.

The purpose of this initiative is to support multidisciplinary consortia of structural biologists, virologists, and computational scientists to resolve complex biological structures, leverage common resources, facilitate new collaborations, and engage and train the next generation of HIV structural biology researchers. Dr. McDonald gave a history and overview of the structure centers which transitioned to NIAID from NIGMS. Currently, there are five Centers for HIV Structural Biology at Pittsburgh, University of CA-San Francisco, Scripps-San Diego, University of Utah-Salt Lake City, and University of Michigan-Ann Arbor. These are multicenter awards and each span several institutions and involve multiple investigators. Highlights of research from the HIV structure center were summarized from four published papers. The rationale for renewal was that the HIV Structure Center program has greatly advanced knowledge of the multimolecular protein and nucleic acid structures critical to HIV replication. Continuation of the program will drive discovery and knowledge in all aspects of HIV-host cell interactions and spur new research into NIAID priorities of HIV therapy, prevention, and cure. Some proposed changes for this initiative include a goal that will encourage restructuring and new competition to drive innovation and public health impact while leveraging the most productive collaborations. This will involve changing the funding mechanism to a U54; broadening scientific scope to include structures related to HIV cure, novel therapeutics, and HIV immunology; adding a developmental core; and increasing the program’s funding to $30M per year to accommodate cutting edge technologies. ARAC reviewers’ comments and suggestions were summarized and responses to them were discussed.

Discussion: None

Ballot Voting Outcome:
9   Approval 
0   Approval with modification(s)
0   Deferral for further information
0   Disapproval
(1 ARAC member in conflict and did not vote)

Understanding HIV Reservoir Dynamics
Eric Refsland, Ph.D.

The purpose of this renewal initiative is to support interdisciplinary collaborations focused on key basic research questions that govern reservoir dynamics during and after cessation of antiretroviral treatment (ART). The rationale for this renewal were that P01s awarded under the first RFA have filled an important niche between small basic research grants and large public-private cooperative agreements, new technologies have evolved since the first RFA, and several key scientific questions remain involving clonal proliferation and correlates of HIV rebound and control. A summary of existing P01 awards from the first iteration of this program, Understanding HIV Rebound, was presented followed by key accomplishments in terms of publications and citations. Highlighted key features of the renewal included an increased focus on reservoir changes over time in relevant cell types and tissues, and the encouraged use of samples from retrospective or parallel studies for clinical research. Some examples of appropriate research topics include: identifying the fundamental drivers of reservoir establishment and maintenance and biomarkers or characteristics of the reservoir that predict HIV rebound or control; and, quantifying the degree of clonal proliferation over time and defining the mechanisms that govern spontaneous in vivo activation of latent infectious HIV provirus. ARAC reviewers’ comments and responses were summarized and addressed.

Discussion: None

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

New Technologies for the In Vivo Delivery of Gene Therapeutics for an HIV Cure
Betty Poon, Ph.D.

The objective of this renewal FOA is to advance strategies to efficiently deliver anti-HIV gene therapies to specific target cells in vivo. While many strategies have been developed for ex vivo delivery of gene therapies against HIV, the primary hurdle continues to be the ability to effectively deliver these therapies to key cell subsets in vivo, such as to HIV-infected cells in tissue sanctuaries. This initiative will support novel delivery platforms for direct in vivo targeting of specific cells and will encourage collaborations between HIV researchers and investigators from other fields such as bioengineering. The background for this proposed initiative included a summary of five research strategies supported in FY 2019 by NIAID and NIMH, including the type of vectors and cellular targets proposed in the applications. The purpose of the renewal and changes from the original RFA were outlined. The scope of the initiative was discussed which included a statement that applications must propose in vivo analytical studies providing key insights into the biological plausibility. For example, analysis of bioavailability, tissue distribution, expression and stability in appropriate animal models. Where this initiative fits in the DAIDS cure studies portfolio also was discussed. The ARAC reviewers recommended approval of this initiative. Their comments and suggestions were summarized and responses to them were discussed.

Discussion

Q: How do you define "cure" here? Is it strictly defined in the FOA?
A: We haven't defined it as to whether it is going to be an ART remission, or a total excision of every single provirus. The latter is our ultimate goal, but at this time is aspirational.

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

Understanding Post-Transcriptional Regulation of Intact and Defective HIV RNA
Gerard Lacourciere, Ph.D.

The objective of this initiative is to explore how RNA chemical modifications impact expression of intact and defective HIV and to identify potential therapeutic targets for future HIV cure strategies. A R61/R33 mechanism is proposed. Some key points for this initiative include: the proviral HIV DNA sequence is highly diverse and resides in heterogeneous cell populations and tissues; recent advances in epi-transcriptomics and single-cell technologies now provide an unprecedented opportunity to characterize the transcript landscape of the HIV reservoir. Also, these technologies could lead to the identification of chemical modifications on HIV RNA and an understanding of how these modifications affect protein expression in different cellular subpopulations. HIV does not express nucleic acid modifying proteins and is dependent on cellular proteins to modify RNA and modifications on HIV RNA are found at higher levels compared to cellular RNA. Therefore, identification of the type and location of all RNA modifications, their incorporation mechanisms and their role in RNA processing could lead the development of novel therapeutic and/or cure strategies. Two modifications that have been identified and characterized on HIV RNA were described. Some areas this initiative will support were listed and included human ex vivo and single cell approaches to define the HIV transcript landscape in different cellular subpopulations harboring intact and defective provirus in the context of ART. The initiative will support studies focused on identifying epi-transcriptomic RNA modifications found on HIV RNA and understanding how these modifications impact viral replication. The ARAC reviewers recommended approval of this initiative. Their comments and suggestions were summarized and responses to them were discussed.

Discussion

Q: Why the R61/R33 mechanism? Perhaps an R21 or R01? 
A: The R61 would be the initial phase for three years that would support the basic research. It would not require any preliminary data and milestones would need to be achieved to advance to the R33 phase after a program assessment of work that can move into the next phase for therapeutic development. 

Other comments:

  • It's a very complex, controversial area and expecting therapeutics to come out of this in the first three years is extremely hopeful; three years for the first phase may be too soon to get to the clinic.
  • In some ways, the R61 is like a hybrid of the R21 and the R01 in terms of the amount of time.
  • The R33 phase can be refocused to not require getting into a druggable target, but to get into some additional mechanistic studies that could further define whether or not you have identified a therapeutic target. We need to think about what is reasonable within a five-year period. An issue is what work to focus on after the first three years.
  • More research on this field is needed. 
  • Concern that this has ring-fenced away competition from other areas. 
  • We do not want to create an artificial advantage for people in this field. The goal is to stimulate research in the field without forcing something that is not feasible. The biphasic approach would allow for grants to stimulate work in this area and allow grantees to be focused. The biphasic approach gives the flexibility to discontinue the research if progress is not made after the first three years. 
  • The R21 mechanism is defined by time and dollars ($275K maximum budget). The R61 would allow greater budgets.
  • Perhaps consider an R01 and require preliminary data. But that would favor researchers already in the field. 

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

Therapeutics Research Program

Understanding and Overcoming Resistance to Broadly Neutralizing Antibodies (bNAbs) Targeting HIV 
Randall Tressler, M.D.

The objective of this new initiative is to better understand mechanisms that contribute to bNAb resistance and strategies to overcome it. In preclinical studies and/or clinical trials, native and engineered bNAbs have been shown to prevent and treat HIV infection, and to produce a sustained virologic response when paired with immune modulators. They are also being engineered to support dosing every three to six months. However, clinical trials have shown that HIV becomes resistant to bNAb mono and dual therapy so there is a need to understand and how to detect, prevent, and overcome this resistance. To meet the objective, we need to understand how changes in the amino acid sequence and glycosylation impact HIV envelope structure and contribute to bNAb resistance. The scope of research was reviewed, and included using a multidisciplinary research team and use of translational and clinical specimens. Results of this research will help inform clinical strategies to overcome pre-existing resistance and prevent emergence of de novo resistance. Out of scope research applications include those that propose clinical trials, studies focused on cellular immunity, or studies focused only on viral sequences. The ARAC reviewers recommended approval and their comments and responses to them were summarized. 

Discussion

Q: The field is evolving to combination bNAbs. How do you envision this would help that?
A: New bNAbs are entering the clinic as are novel combinations of antibodies. Unfortunately, none of the two or three bNAb combinations currently cover 100 percent of the pseudoviruses in the standard panel, and even when dual bNAbs are used in individuals prescreened for sensitivity to both bNAbs we see emergence of resistant viruses when bNAb concentrations are therapeutic and as bNAb levels wane. Therefore, we need to better understand what contributes to bNAb resistance, how to detect it, and strategies to overcome it, or identify assays that are better able to detect resistance. As more broad and potent bNAb combinations move into human clinical trials, I believe data from this initiative will benefit from this research, and as resistant viruses emerge in new studies, they can be studies in this initiative.

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

Vaccine Research Program

HIV Vaccine Research and Design (HIVRAD) Program
Bimal Chakrabarti, Ph.D.

The objective of this renewal initiative is to support multidisciplinary projects beyond the exploratory stage in addressing important unanswered scientific questions relevant to AIDS prophylactic vaccine discovery research. This is the program’s primary funding instrument to support highly innovative, technically diverse, and most importantly adept collaborative groups, often employing NHP and other animal models to evaluate, anticipate, and overcome obstacles in designing and testing successful candidate HIV vaccines. This was further described in a list. Some HIVRAD history and program highlights were listed and discussed. These included: 

  • Isolation, characterization, development of clade A and C envelope proteins immunogens 
  • Development and optimization of the SOSIP envelope protein platform- clinical trial, HVTN 137 (SOSIP)
  • Determine that CMV vectors violate CD8+ T-cell epitope recognition paradigms. This will soon be used in clinical trials

The ARAC reviewers’ comments and responses to them were summarized. 

Discussion

Q: Is it useful to say how HIVRAD has impacted other fields of vaccine development?
A: Through the HIVRAD program, over many years, several technologies, assays and methodologies have been developed to design, test the immunogens in small animals and in nonhuman primates.

Earlier today, Dr. Mascola and Dr. Fauci mentioned the current strategies and technologies, which are being used to combat the COVID-19 epidemic. It is clear from their presentations that these strategies and technologies, such as stabilization of trimeric “S” protein of SARS-CoV-2 for immunogen design and isolation of potent neutralizing antibodies for prophylactic and therapeutic purposes are the outcome of research through HIVRAD funding over the years. This suggests that the vast knowledge accumulated through HIVRAD funded research is also applicable for preventive or therapeutic purposes for other diseases. 

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

Public Comments

To date, no public comments have been received in writing. Due to the virtual meeting format, public comments will be accepted over the next two weeks. Comments may be submitted in writing to the Executive Secretary, as noted in the Federal Register Notice. Any comments received in the coming weeks will be incorporated into the meeting minutes. 

No public comments were received.

Adjournment

Drs. Freedberg and Dieffenbach thanked the ARAC and community members and DAIDS staff and adjourned the meeting at 4:33 p.m.

VII. Adjournment

The meeting of the Council adjourned at 4:33 p.m., on Monday, June 1, 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

08/18/2020

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

08/18/2020

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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