NIAID Council Minutes—January 25, 2021

The 197^th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened virtually at 10:30 a.m. on Monday, January 25, 2021. Dr. Hugh Auchincloss, principal deputy director, National Institute of Allergy and Infectious Diseases (NIAID) presided as acting chair.

In accordance with the provisions of Public Law 92-463, the meeting was open to the public from 10:30 a.m. to 11:15 a.m. and from 12:30 p.m. to 4:32 p.m. The meeting was closed to the public from 8:00 a.m. to 10:30 a.m. and from 11:15 a.m. to 11:30 a.m. for review and consideration of individual grant applications. Notice of the meeting was published in the Federal Register.

Meeting Attendees

Table of Contents

I. Review of Grant Applications
II. Remarks of the Director, NIAID—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 5,678 research and training applications with primary assignment to NIAID for a requested amount of $1,828,009,167 in first-year direct costs and recommended approval of 2,579 applications with $950,086,541 in first-year direct costs.

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

Dr. Anthony Fauci opened the Council session by welcoming visitors to the meeting. He introduced two Division of Allergy, Immunology, and Transplantation (DAIT) ad hoc members: Dr. Ignacio Sanz, professor of medicine and pediatrics, chief of the Division of Rheumatology, and director of the Lowance Center for Human Immunology at Emory University; and Dr. Stephen Harrison, Giovanni Armenise-Harvard Professor in Basic Biomedical Science at Harvard.

Consideration of Minutes of Previous Meeting

Council considered the minutes of the September 14, 2020 meeting and concepts that had been presented and approved them as written.

Appointments and Organizational Changes

Dr. Fauci summarized some of President Biden’s recent health-related appointments and nominations. 

Dr. Eric Lander has been nominated as director of the Office of Science and Technology Policy and will serve as Presidential Science Advisor.

Xavier Becerra has been nominated for secretary of HHS, and Andrea Palm has been named deputy HHS secretary. Dr. Vivek Murthy has been nominated to serve as U.S. surgeon general, and Dr. Rochelle Walensky is the new director of CDC. Dr. Janet Woodcock has been named acting FDA commissioner.

President Biden named several people to positions related to the administration’s COVID-19 response. Jeff Zients is coordinator of COVID-19 response and counselor to the President; Dr. David Kessler is chief science officer of the administration’s COVID-19 response; and Dr. Marcella Nunez-Smith is the COVID-19 equity task force chair. 

Dr. Francis Collins will continue as NIH director, and Dr. Fauci is chief medical advisor to the President.

President Biden made several key appointments to the National Security Council (NSC). Jake Sullivan was selected to be national security advisor, Dr. Beth Cameron is senior director for global health security and biodefense, and Dr. Hilary Marston will be working with Dr. Cameron on a 12-month detail as director of medical bio-preparedness and response.

Staff and Organizational Changes

Dr. Jill Harper is the new NIAID deputy director for science management. She succeeds Dr. John McGowan who retired in December after 40 years of federal government service. 

Laura Gent is the new budget officer, deputy director of the Office of Mission Integration and Financial Management (OMIFM), and acting director of OMIFM. She replaces Wayne Crum who retired after 40 years at NIH; 30 of them with NIAID.

In OMIFM, two new branch chiefs have been appointed. Angie Chon-Lee is the new chief of the AIDS Budget and Financial Management Branch, and Ruby Lee is the new chief of the Infectious and Immunologic Diseases Budget and Financial Management Branch.

Joyelle Dominique is the new director of the Office of Global Research, and John Tierney has been appointed director of the Office of Clinical Research Policy and Regulatory Operations in the Division of Clinical Research. 

In the Division of AIDS, Dr. Michael Eller has been named chief of the Vaccine Translational Research Branch in the Vaccine Research Program. 

In the Division of Extramural Activities (DEA), Dr. LeShawndra Price joined NIAID as the new director of the Office of Research Training and Special Programs. She replaces Dr. Paula Strickland who retired after almost 30 years at NIAID. 

Dr. Fauci announced four new branch chiefs in DEA: Dr. Ronald Otten, branch chief, AIDS Review Branch, Scientific Review Program (SRP); Dr. Louis Rosenthal, branch chief, Immunology Review Branch, SRP; Jason Lundgren, branch chief, Small Business Innovation Research/Small Business and Technology Transfer and Training Grants Branch, Grants Management Program (GMP); and Tamia Powell, branch chief and division coordinator for the Division of Allergy, Immunology, and Transplantation, GMP.

Tributes and Awards

Dr. Fauci paid tribute to Dr. John G. Bartlett, professor of medicine at Johns Hopkins University School of Medicine, who recently passed away. He led efforts to understand, prevent, and treat people with HIV; was the first to direct clinical trials in Baltimore; and pioneered the development of dedicated inpatient and outpatient medical care for people with HIV.

Meetings and Events

Dr. Fauci reported on virtual meetings that have been held with international delegations and health officials. NIAID scientists have held COVID-19 research meetings with Chinese colleagues, and Dr. Fauci met with officials from the United Kingdom, South Korea, and Ecuador.

Budget Update

The President is required to submit his annual budget to Congress by the first Monday in February. As the executive branch transitions to a new administration, this will be delayed for several months.

Congress approved a spending package for fiscal year (FY) 2021 that the President signed into law on December 27. NIH received a $1.25 billion increase from FY 2020, which makes this the sixth consecutive year that NIH has received a significant increase.

In addition to the annual budget amount, the bill also includes another $1.25 billion in supplemental spending to NIH for coronavirus response and relief that is available until FY 2024. Of that total, $1.15 billion supports research and clinical trials related to the long-term effects of COVID-19. The remaining $100 million continues support of the Rapid Acceleration of Diagnostics (RADx) program.

NIH received an overall increase of 3.0 percent. NIAID received a 3.1 percent increase, which included an additional $20 million for developing a universal influenza vaccine; an increase of $10 million for the Centers for AIDS Research as part of the Trump administration’s initiative for Ending the HIV Epidemic; a $10 million increase to combat Lyme disease and related tickborne illnesses; and $40 million to be divided evenly among the 12 Regional Biocontainment Labs to continue efforts to prevent, prepare for, and respond to infectious disease outbreaks.

Dr. Fauci summarized NIAID’s FY 2021 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 20 percent from their planned budget level. Our estimated success rates for research project grants will be 22 to 24 percent.

Dr. Fauci gave an overview of the funding NIAID received through two emergency supplemental funding packages: the Coronavirus Aids, Relief, and Economic Securities (CARES) Act and the Coronavirus Preparedness and Response Supplemental Appropriations Act. The emergency supplemental funding provided NIAID with $1.5 billion and is available until September 30, 2024. 

NIAID has provided $812 million in support of extramural and intramural investigators to address the scientific areas that are most critical to understanding COVID-19 and advancing medical countermeasures. The remaining $720 million will be awarded to address the most urgent public health and scientific research needs, with a significant portion supporting ongoing extramural and intramural projects and $223 million allocated for infrastructure needs at NIAID’s Vaccine Research Center (VRC) in Bethesda and Rocky Mountain Laboratories in Hamilton, Montana. 

NIAID is also a key partner in NIH's Accelerating COVID-19 Therapeutic Interventions and Vaccines, which is operating in conjunction with HHS's Operation Warp Speed to coordinate the government's response and work with private companies to accelerate developing, manufacturing, and distributing COVID-19 vaccines, therapeutics, and diagnostics.

Legislative Update

Dr. Fauci outlined congressional leadership changes following the recent elections. In the Senate, Senator Chuck Schumer is now the Majority Leader, and Senator Mitch McConnell is Minority Leader. In the House of Representatives, Representative Nancy Pelosi remains Speaker of the House, and Representative Kevin McCarthy continues to serve as House Minority Leader. 

Dr. Fauci provided leadership updates for congressional committees and subcommittees in the House of Representatives. Senate committee leadership had not been announced. 

On September 23, Dr. Fauci testified before the Senate Health, Education, Labor, and Pensions Committee at a hearing on the ongoing federal response to the pandemic. 

On September 25, NIAID hosted a virtual tour of the VRC for republican members of the House of Representatives. NIH Director Dr. Francis Collins and Dr. Fauci provided remarks about VRC’s critical role in addressing emerging and reemerging infectious diseases, including COVID-19. VRC Director Dr. John Mascola, along with VRC Deputy Directors Drs. Barney Graham and Julie Ledgerwood, provided an overview of VRC’s extensive research on coronaviruses and rapid development of the mRNA-1273 COVID-19 vaccine.

On September 30, Dr. Fauci held a virtual discussion with the Congressional Hispanic Caucus on the disproportionate impact of COVID-19 on minority communities, particularly Latino and Hispanic populations, and the importance of including racial and ethnic diversity in clinical trials. He and Dr. Collins also discussed the disproportionate impact of COVID-19 on communities of color with the Black, Hispanic, Asian Pacific American, and Native American Caucuses.

Dr. Fauci thanked NIAID staff who have participated in many briefings and events on his behalf.

Other Information Items

Dr. Fauci presented the most recent statistics on COVID-19 cases and deaths globally and in the United States. He summarized data from the three major infection surges (late winter and early spring 2020, early summer 2020, and late fall 2020) and noted that hospitalizations followed a similar pattern.

A considerable amount of research is now focusing on post-COVID-19 syndrome where even after clearing the virus a percentage of people experience lingering health issues. On December 3 and 4, 2020, NIAID held a virtual Workshop on Post-Acute Sequelae of COVID-19 with breakout sessions focused on six areas: cardiovascular, pulmonary, renal/GI/metabolic, neurologic/psychiatric, immunologic/rheumatologic, and pediatric.

Dr. Fauci noted updates on advances in COVID-19 home tests and therapeutics. He presented the extraordinary timeline from the availability of the sequence of SARS-CoV-2 to the development of a safe and effective vaccine. The Moderna and Pfizer vaccines both have been approved for emergency use authorization. 

He concluded by mentioning the National Strategy for the COVID-19 Response and Pandemic Preparedness and recommended actions to control and end the pandemic.

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

Dr. Rotrosen welcomed the subcommittee members to the 197^th meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting.

Dr. Rotrosen presented the following scientific and Division activities:

Staff and Organizational Changes

Dee Gamliel, M.S., Ms. Gamliel joined the Office of Program Planning, Operations and Scientific Information (OPPOSI) as a program analyst in the Program Operations Unit in October 2020. She received a B.S. in Health & Wellness (renamed Public Health) from State University at Buffalo State, followed by a master’s degree from Southern California University of Health Sciences. She worked for three years as a health specialist at the National Center for Complementary and Integrative Health, and then for seven years as a project officer at the Health Resources & Services Administration (HRSA) in the HIV/AIDS Division. With her skills in grants management, data analysis, concept clearances, notice of funding opportunity (NOFO) review, and writing she will be a great asset to OPPOSI.

Tatyana Vaysman, M.D., Dr. Vaysman joined the Allergy, Asthma, and Airways Biology Branch (AAABB) in November 2020, as a project manager. Dr. Vaysman received an M.D. from the Crimea Medical University (Ukraine). She started working in research at Parexel International as a clinical research associate. Thereafter, she continued her career at Cenexel/CBH Health as a clinical research coordinator and later as a clinical trials manager, before accepting a position at NIAID. Her experience with clinical protocol and operations manual development, staff training, and safety oversight will be valuable to the AAABB team.

Caeden Dempsey, M.P.H., M.S.N., R.N., Mr. Dempsey joined the Allergy, Asthma and Airways Biology Branch in January 2021, as a project manager. He attended Johns Hopkins University where he earned a BSN followed by master’s degrees in public health and nursing. Upon graduating, he worked as a nurse educator and then a clinical specialist, focusing on quality improvement and patient safety at MedStar Washington Hospital Center in Washington, DC. In 2017, he joined the NIAID intramural research team in the Food Allergy Research Unit of the Laboratory of Allergic Diseases. There he served as a research nurse coordinator, assisting in research focusing on IgE-mediated food allergy and genetic diseases associated with the development of allergy.

Division Activities

Allergy, Asthma, and Airway Biology Branch

2020 Annual Asthma and Allergic Disease Cooperative Research Center Face to Face Meeting (AADCRC). On October 29 and 30, 2020, NIAID sponsored the 15^th annual meeting of the AADCRC investigators virtually. The two-day meeting of PIs, co-investigators, students, and program staff included 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 young investigators supported by the opportunity fund.

Basic Immunology Branch

Molecular Mechanisms of Combination Adjuvants (MMCA). On October 8, 2020, NIAID virtually held the annual meeting of the Molecular Mechanisms of Combination Adjuvants Program. 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 systems immunology to understand host immune responses to adjuvants and adjuvanted vaccines.

Systems Immunology Program. On October 9, 2020, the annual programmatic meeting of the DAIT Systems Immunology U19 Cooperative Agreement program was held via videoconference. The overall goal of the program is to identify new genes, pathways, and mechanisms that are critical for initiating, maintaining, and controlling immune responses to pathogens, adjuvants, or vaccines. The three awardees (Harvard University: Arlene Sharpe; University of North Carolina: Ralph Baric and Mark Heise; The Scripps Research Institute: Richard Ulevitch) and their group members presented their progress. The scientific meeting was followed by a Steering Committee meeting, which included the principal investigators from each U19 group and NIAID staff, to discuss the awardees plans for the coming year and new collaborations between the three centers.

Adjuvant Discovery Program. On October 20, 2020, the kick-off meeting for the fourth iteration of the Adjuvant Discovery Program was held virtually. NIAID awarded six contracts and each group is conducting high throughput screening campaigns to identify small molecule-, peptide-, or aptamer-based agonists of innate immune pathways that have the potential to enhance vaccine-induced immune responses. Two contractors, using different compound libraries and screening approaches, are screening for novel activators of the STING signaling pathway. In search of adjuvants that will address the unique immunological differences between adults versus newborns and the elderly, one contractor screens small molecule immune stimulators for those vulnerable populations. Recognizing the role of exosomes in cell signaling and activation, one contractor is screening small-molecule compound libraries for inducers of immunostimulatory exosomes. Also pursuing a nontraditional adjuvant target, one contractor is establishing libraries of potential activators of the IL1-receptor that work by cross-linking the receptor subunits. Finally, one contractor is screening compound libraries for inhibitors of inflammatory pathways that are being explored as co-adjuvants for traditional PRR-agonists, to modulate adjuvant-induced inflammation while promoting adaptive, vaccine-induced immune responses.

Impact of Initial Influenza Exposure on Immunity in Infants. On October 28, 2020, investigators and their teams awarded under this program met virtually for their second annual program progress meeting. Two projects are supported under this program that is a partnership between the Division of Microbiology and Infectious Diseases and the Division on Allergy, Immunology and Transplantation, NIAID. The goal of the overall program is to establish, follow, and characterize longitudinal cohorts of infants to determine how initial and repeated natural influenza infections and/or influenza vaccinations shape infant and childhood immunity to future influenza exposures. The awarded groups are led by a) Paul Thomas (St. Jude Children’s Hospital) and Aubree Gordon (University of Michigan) and b) Mary Staat (Cincinnati Children’s Hospital Medical Center). In addition, Open Philanthropy is co-sponsoring the Cincinnati Children’s Hospital study to support innate immunity and additional systems biology analyses at Stanford University. Investigators presented recent updates and progress in each of their programs, including SARS-CoV-2/COVID-19 studies added in summer 2020 to both awardees. The meeting encouraged investigators to exchange ideas and to foster collaborations within the program. 

Computational Models of Immunity Meeting. October 29, 2020, the kick-off meeting of the Computational Models of Immunity Program was held as an online web-based meeting. Six single-project cooperative agreements were awarded under this program. Investigators include those from Columbia University, Emory University, the Icahn School of Medicine at Mt. Sinai, the La Jolla Institute for Immunology, the University of California, San Francisco, and Vanderbilt University. Proposed projects and preliminary study data were presented; investigators were introduced and connections were made for potential future collaborations between centers.

Immune Mechanisms of Protection Against Mycobacterium tuberculosis Center (IMPAc-TB). On November 18 and 19, 2020, the first annual meeting of the IMPAc-TB contracts was held via video conferencing. Each of the principal investigators presented an overview of their programs and the accomplishments achieved and challenges encountered in the first full year of award. The overarching goal of the IMPAc-TB program is to identify and characterize immune responses required to protect a host from initial Mycobacterium tuberculosis (Mtb) infection, establishment of latent infection or progression to active tuberculosis (TB) disease. IMPAc-TB is the first NIAID trans-divisional program supporting studies to better understand TB immunology. The contractors are using murine, nonhuman primates, and human models; functional assays; and comprehensive immunologic approaches to help the broader TB vaccine community translate findings into improved vaccine strategies.

Immunity in Neonates and Infants. On December 2 and 3, 2020, investigators awarded under the Immunity in Neonates and Infants program met virtually for their annual meeting. Fifteen projects are supported under this program that is a partnership among NIAID, National Institute of Child Health and Human Development, and National Institute of Environmental Health Sciences. The goal of this program is to better understand neonatal and infant immune regulatory mechanisms in response to commensal bacteria, allergens, infectious agents (including HIV), vaccines, or environmental pollutants. Investigators reported current progress on their projects and recent updates on new collaborations that were initiated during the year. The meeting provided a venue for investigators to exchange ideas, foster collaborations, and leverage resources and expertise to advance the field. 

Cooperative Center for Human Immunology (CCHI) Program. On December 8 and 9, 2020, the CCHI annual meeting was held virtually. The program is to support 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. Investigators from all eight centers presented their research progress, including recent updates on the COVID-19 studies supported by the supplement awards. Ten awardees who received the CCHI Infrastructure and Opportunity Fund also presented their work. In addition to the live meeting, a virtual poster session was held for the week, and it provided an opportunity for trainees to showcase their research. Among them, ten of the posters were selected for short talks. The CCHI program is continuing to provide a platform for building collaborations, sharing the best practices, and leveraging resources among the groups.

Characterizing and Improving Humanized Immune System Mouse Models. On December 11, 2020, the kick-off meeting of the new program to characterize and improve humanized immune system mouse models was held virtually. Three contracts were awarded. Each group presented plans to develop, optimize, and test the ability of non-fetal human tissues (cord blood hematopoietic stem cells, neonatal tissue) or porcine thymus tissue transplanted into mice to ensure reproducible immune reconstitution and maintenance in blood, lymphoid, and non-lymphoid tissues. Comprehensive characterization will be conducted in models that include vaccination, infection, or allograft rejection. Training sessions will be hosted annually by each contractor to share knowledge and techniques for engraftment and characterization of humanized mouse models developed under this contract. 

Maintaining Immunity After Immunization Annual Meeting. On December 15, 2020, the annual progress update for the Maintaining Immunity after Immunization program was held as a videoconference. 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. The annual meeting provided a venue for the project investigators to give an update on progress, and to develop scientific collaborations with each other to enhance program success.

Radiation and Nuclear Countermeasures Program

Immune Dysfunction from Radiation Exposure Workshop. On September 9 and 10, 2020, NIAID sponsored a virtual workshop, with planning input from the DAIT Basic Immunology Branch, the Radiation Injury Treatment Network (RITN), and BARDA colleagues. The meeting brought together leaders in the field of radiation biology who study immunological responses to radiation, along with other prominent specialists studying a range of immune topics that spanned thymus function and regeneration to immune reconstitution and immune system/microbiome interactions. The scientific sessions explored new perspectives for interpreting how various systemic injury-like disease states, such as radiation exposure, may lead to impaired homeostasis and immune dysfunction. Speakers and attendees participated in discussion sessions to identify gaps in knowledge and propose potential topics for new investigation, as well as possible new approaches for interventions. The meeting was well attended, with over 250 registrants who provided highly positive post-meeting feedback. A meeting report for possible publication in Radiation Research is in preparation for 2021.

66^th Annual Meeting of the Radiation Research Society. From October 18 to 21, 2020, the RNCP sponsored poster and presentation sessions at the Radiation Research Society virtual meeting. Sessions explored topics related to Radiation Emergency Medical Management, Mitigators of Normal Tissue Injuries Developed by NIAID, Biodosimetry, and Animal Models. RNCP staff provided an oral presentation and served as symposium moderators. The meeting was well attended, with RNCP-funded scientists contributing more than 60 posters and oral presentations.

2020 Annual Update Meeting for the Centers for Medical Countermeasures against Radiation Consortium (CMCRC). On November 30 and December 1, 2020, the CMCRC annual meeting was held virtually, marking the start of the 4th iteration of the CMCRC that includes a new center (University of Maryland School of Medicine) and two continuing centers (Columbia University and Duke University). Each of the centers provided an overview of the research they will pursue during this funding period. The meeting offered an opportunity to showcase the portfolio to other key stakeholders from partner federal government agencies (NCI, BARDA, NASA, DoD and FDA). In addition, the meeting fostered dialog and collaboration among the CMCRC investigators and program staff regarding future research and development directions. Also present were four members of the External Advisory Board, who provided their insight and advice about the research discussed.

FY 2022 SBIR Contract Topics Presented to Division Advisory Council

The subcommittee endorsed and unanimously approved four NIAID Data Science SBIR contracts topics:

1. Advanced and Immersive Visualization Tools for Infectious, Immunologic, and Allergic Research
2. De-Identification Software Tools and Pipelines for Human Clinical Research Data
3. Data Science Tools for Infectious and Immune-Mediated Disease Research
4. Development of Digital Tools to Combat Misinformation Spread About Infectious Disease Treatments and Vaccines

The subcommittee endorsed and unanimously approved five additional SBIR contract topics:

1. Adjuvant Discovery for Vaccines and for Autoimmune and Allergic Diseases
2. Production of Adjuvants Mimics
3. Reagents for Immunologic Analysis of Non-Mammalian and Underrepresented Mammalian Models
4. Adjuvant Development for Vaccines and for Autoimmune and Allergic Diseases
5. Informatics Tools and Services for Clinical Data Harmonization

FY 2022 Research Concept Clearances Presented to Division Advisory Council

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

1. Emerging Science and Technologies in Transplantation Research (U01, Clinical Trial Not Allowed)
   The goal of this initiative is to promote the application of emerging science and technologies to transplantation immunology. It will encourage and stimulate transplantation immunology research in three priority areas: 1) microbiota and alloimmunity; 2) targeted therapeutic delivery; and 3) in vivo imaging.
2. Radiation-Induced Immune Dysfunction (U01, Clinical Trial Not Allowed)
   Research funded by this initiative will examine the effects of radiation exposure on the immune system and explore possible treatments for immune dysfunction.
3. Research on Bat Immunology (R21, Clinical Trial Not Allowed)
   The purpose of this initiative is to support research to characterize cellular and molecular constituents of the bat immune system and to understand protective innate and adaptive immune mechanisms in bat species with the potential for hosting zoonotic infections in humans.

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 25, 2021. She acknowledged the service of the three retiring DMID Subcommittee members, Drs. Stan Lemon, Robin Patel, and Mark Feinberg, and thanked them for their service. She provided a DMID personnel update, recognizing new staff appointments made in the Division since the last Council meeting, including Paul Eder, Lisa Wei, and Jeremy Star in the Office of Biodefense, Research Resources, and Translational Research (OBRRTR); Erica Sondergaard in the Office of Clinical Research Affairs; Cristina Cardemil in the Office of Clinical Research Resources; and Sonja Crandon in the Respiratory Diseases Branch.

Following staff introductions, Dr. Erbelding reported on several activities, including:

• Results of an NIAID-sponsored, randomized, double-blind, placebo-controlled trial enrolling children with community-acquired pneumonia, which demonstrated that short-course antibiotics were equivalent to standard of care in outcomes and superior because of less selection pressure.
• Publication of Department of Health and Human Services strategic plans addressing viral hepatitis and sexually transmitted infections, respectively, and a five-year Vaccines National Strategic Plan. She reported that several DMID staff members were involved in the development of these documents, which are available on the HHS website.
• Initiation of a Phase II clinical trial to evaluate Bexsero, which is a Group B meningococcal vaccine, as a possible gonorrhea vaccine.

Dr. Erbelding presented a late-breaking FY 2021 concept for clearance, in response to a directive in the most recent NIH appropriations bill, that would provide an opportunity for the Regional Biocontainment Laboratories (RBLs) established by NIAID to request support for upgrades to established RBL facilities and building systems to facilitate the conduct of biomedical research on infectious diseases, including infectious disease outbreaks.

Finally, Dr. Erbelding presented four topics for inclusion in the 2022 Small Business Innovation Research (SBIR) Contract Solicitation for the Subcommittee’s consideration. All were approved by the Subcommittee:

1. Development of Rapid POC Diagnostics for Treponema pallidum to develop a rapid, point-of-care diagnostic capable of detecting T. pallidum directly from patient specimens.
2. Improving Sample and Library Preparation for Next-Generation Sequencing (NGS)-Based Diagnostics in Infectious Diseases to develop a generalizable procedure for sample extraction and library preparation directly from human samples for faster and more accurate NGS diagnostics for infectious diseases.
3. Development of monoclonal antibody-mediated interventions to Combat Malaria to develop monoclonal antibodies (mAbs) or mAb-based candidates for prevention or treatment of Plasmodium falciparum or Plasmodium vivax malaria.
4. Point-of-Care (POC) Diagnostics for Antimicrobial Resistant (AMR) Enteric Bacterial and Parasitic Pathogens to develop a rapid point-of-care diagnostic capable of detecting infectious enteric pathogens and associated antimicrobial resistance profile(s) directly from patient specimens.

Update: DMID SARS-CoV-2/COVID-19 Research Update: Dr. Emily Erbelding, director, DMID and Dr. Cristina Cassetti, deputy director, DMID

Dr. Erbelding described ongoing clinical activities, updating Subcommittee members on vaccine and therapeutic efforts. She provided an update on the leading COVID-19 vaccine candidates that were in late-stage development, noting that the Moderna and Pfizer-BioNTech vaccines had already received emergency use authorization by the FDA. She acknowledged the concerns expressed by a Subcommittee member regarding the impact new variants may have on vaccine effectiveness and informed the Subcommittee that NIAID was collaborating with Moderna to test a vaccine booster shot aimed at addressing the worrisome variants that have been identified. 

Dr. Erbelding noted that the Institute had developed a Pandemic Preparedness and Response Research Plan in 2019 that discussed the importance of harnessing collaborations across all NIAID divisions and others in the event of an infectious disease outbreak. She reported that intramural and extramural divisions have worked well together during the current COVID-19 pandemic, forming collaborations that have been instrumental in facilitating the conduct of very large efficacy trials. She noted that a number of important unanswered research questions remain for COVID-19 vaccines, e.g., whether the vaccines are safe and efficacious in children and in pregnant women, and stated that DMID will continue to advance research in these areas. Finally, she provided an update on the Adaptive COVID-19 Treatment Trial, an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19 to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19.

Dr. Cassetti provided several updates on DMID’s preclinical research efforts, including an ongoing collaboration with the Biomedical Advanced Research and Development Authority (BARDA) and others to conduct a large nonhuman primate study to look at the correlates of protection of four different vaccine candidates to understand in detail the immune responses induced by these vaccines. She also described DMID efforts to leverage existing preclinical service contracts to carry out a number of critical activities, including the development of standardized assays and new animal models to understand the pathogenesis of SARS-CoV-2 and evaluate potential countermeasures. She also described how DMID has been able to leverage existing research networks such as the Centers of Excellence for Influenza Research and Surveillance to conduct important COVID-19 studies, including natural history studies in humans to determine the longevity of immune responses. In closing, she also noted there are many unanswered research questions at the basic and preclinical stages and that DMID will continue to conduct research to address these gaps.

FY 2022 Concepts Presented for Clearance:

NIAID Career Development for Advancing the Careers of a Diverse Research Workforce–this concept seeks to further promote diversity in research training and education programs that could result in the participation and retention of underrepresented groups in biomedical research. The program would complement the overall research portfolio and provide a unique program within NIAID that encompasses immunologic, allergic, and infectious disease research at the undergraduate, graduate, postdoctoral, and junior faculty levels. The Subcommittee approved the concept.

Centers for Research on Structural Biology of Infectious Diseases–this concept would continue support for the NIAID Centers for Research on Structural Biology for Infectious Diseases (CRSTL-ID) to determine three-dimensional (3D) molecular structures of proteins from priority and emerging human pathogens. The DMID Subcommittee members were very supportive of the proposed renewal, which will provide a service for structural determination of proteins that play an important biological role in human pathogens and infectious diseases and contribute to structure-based vaccine design and drug discovery. The Subcommittee members noted the need for increasing the visibility of the program across the infectious disease research community by expanding outreach efforts to better market the services offered by the centers as widely as possible. The Subcommittee members also encouraged program to harmonize the websites across the awarded centers to provide clear and consistent guidance to the community regarding the process for requesting services. Finally, there was enthusiasm for the name CRSTAL-ID for the renewal of the Structural Genomics Centers for Infectious Diseases. Program clarified that while a majority of the structures are solved by x-ray crystallography, the centers are now solving structures by Cryo Electron Microscopy as well. The Subcommittee approved the concept. The Subcommittee approved the concept.

DMID Clinical Materials Services–this concept would continue the management and operation of a cGMP-compliant clinical materials services facility for DMID-funded clinical research. The Subcommittee members acknowledged the need to maintain the Clinical Materials Services program, which provides for the management and operation of a cGMP-compliant clinical materials services (CMS) facility for DMID-sponsored clinical trials, a critical need. Program staff shared metrics and accomplishments related to the current COVID-19 outbreak. The Subcommittee approved the concept.

DMID Regulatory Affairs Support–this concept would continue scientific, regulatory, technical, project management, and administrative assistance for a broad spectrum of regulatory activities in support of DMID’s clinical research activities. The Subcommittee voiced support for the Regulatory Affairs Support concept, noting that the scope of work under this program was very impressive, particularly with regard to the COVID-19 efforts described. The Subcommittee had questions regarding the funding mechanism and the scope. Program outlined the scope of work covered by this program, which is supported through a contract mechanism. It was also clarified that the services provided under the program are for internal NIAID use and not available to external partners. Council members also questioned the robustness of the current data systems that support the program, and whether there were back-up systems in place. Program responded that there are strong back-up systems in place. Council members also questioned the competitiveness of this concept. Program responded that this will be an open solicitation, and therefore very competitive. The Subcommittee fully supported the concept.

Basic Research to Understand the Emerging Threat of Bunyavirus Infections–this concept would promote basic research into molecular and cellular mechanisms of viral emergence of bunyavirus infections. There was strong enthusiasm for the concept with the Subcommittee noting that supporting research on this group of important and under-investigated viral pathogens would lead to valuable returns. The Subcommittee members agreed the field was ripe for expanding basic research discoveries that could be leveraged to respond to future outbreaks or epidemics. They also highlighted the benefit of cohorts established under the NIAID-supported Centers for Research on Emerging Infectious Diseases (CREID) and ongoing COVID-19 research projects that could be leveraged by investigators funded under this initiative. Program staff noted that there are reference strains that would be available to investigators supported under the program through the NIAID-supported microbiology and infectious diseases resources repository (BEI Resources). The Subcommittee voted in support of the concept.

Systems Approach to Understand Mechanisms of Heterogeneous Response to Influenza–this concept would support efforts to identify mechanisms behind varying responses to influenza infection and vaccination using computational tools. The Subcommittee members expressed strong support for the concept, noting that bringing together the complementary fields of infectious diseases and computational science has the potential to yield exciting and important results. They also noted that the program will elevate the role of computational scientists while leveraging existing investments by using data developed through programs funded by NIAID and others. The Subcommittee members recommended outreach to computational scientists, including those currently focused in other fields, once the funding announcement is published to ensure that proper expertise is recruited. The Subcommittee members also recommended emphasizing in the announcement that applicants should focus on the development and use of tools and not modeling approaches. The Subcommittee approved the concept. 

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 A. Freedberg, M.D., M.Sc., (Chair)

Dr. Freedberg welcomed everyone and the ARAC members approved the minutes of the September 14, 2020 meeting.

Director’s Report and SBIR Contract Topics

Carl Dieffenbach, Ph.D.

Dr. Dieffenbach recognized the passing of Catherine Wilfert and John G. Bartlett, M.D. It was noted that Francis S. Collins M.D., Ph.D., will continue as NIH director; this is the third President that Dr. Collins has served under. Michael Eller, Ph.D. was welcomed as the new chief of the Vaccine Translational Research Branch for the Vaccine Research Program in the NIAID Division of AIDS (DAIDS).

Budget Update

The President’s Budget Request for the FY 2022 will be delayed until sometime between March and May due to the change in administration. On December 27, a new federal budget for FY 2021 was passed by the House and Senate and signed by the President. This omnibus and coronavirus response and relief bill included $43 billion in NIH funding for FY 2021 and supplemental coronavirus funding of $1.25 billion available until September 30, 2024. It was a 3 percent increase, and this represents the sixth consecutive year of a substantial increase. A table summarizing how the budget was distributed across the NIH institutes and centers highlighted a 3.1 percent increase in NIAID funding. The NIAID FY 2021 financial management plan listed various paylines where the R01 paylines would be held to the 14^th and 18^th percentiles for established and new PIs respectively. No adjustments were made to awards for noncompeting and competing grants, but there will be a cut in competing research initiatives of up to 20 percent. Estimated success rates across the Institute are expected to be between 22-24 percent.

For AIDS funding specifically, NIAID received a 0.9 percent increase that totals $15.73M, with $10M earmarked for Ending the HIV Epidemic (EHE) projects through the CFARs and other Centers Programs at NIH that we collaborate with.

NIAID COVID-19 Emergency Supplemental

A summary table of where the emergency supplemental budget in FY 2020 was spent was reviewed. This covered the research areas including the NIAID infrastructure with the related spent and forecasted spending in 2020. Much of this funding has already been committed for multi-year awards. 

COVID-19 Operation Warp Speed

DAIDS has been the beneficiary, particularly in the area of clinical trials, to be collaborating with Operation Warp Speed (OWS), part of BARDA. This has helped to accelerate the work being done on vaccines and therapeutics. Spending from inception to January 2021 for the vaccines and therapeutics research areas in OWS was approximately $1.2 billion. Credit was given to the DAIDS staff and collaborators in other parts of the Institute for continuing their work on HIV in addition to moving forward on developing coronavirus vaccines and therapeutics.

Scientific and Programmatic Updates

NIH research highlights for HIV in the last year were presented. This included:

• The long-acting injectable form of HIV prevention (cabotegravir) outperformed the daily oral pill of Truvada in MSM and transgender women in one study and in preventing HIV acquisition in cisgender women in another study. In the study of cisgender women, it was noted that Truvada performed better than in previous clinical trials and was efficacious in preventing HIV acquisition. FDA licensure is in progress.

Completed Recompetition of the HIV/AIDS Clinical Trials Networks
NIAID announced the renewed funding of four HIV/AIDS clinical trials networks (ACTG, HPTN, HVTN and IMPAACT) effective December 1, 2020 and these awards will run through 2027. These awards were made during the time of the COVID global pandemic, on budget, on time and on schedule. 

NIH Accelerating COVID Therapeutic Interventions and Vaccines (ACTIV)
The ACTIV public-private partnership formed by the NIH OD to examine the acceleration of therapeutics and vaccines development through interactions of various ACTIV subgroups (Preclinical, Clinical Trials, Therapeutics and Vaccines) and ACTIV Committees. A summary, using a schematic diagram, provided an overview of this complicated approach comprising clinical trials ACTIV (1 through 5). This approach attempts to utilize all the NIH clinical trials’ capacity to address the numerous questions that exist in the context of coronavirus disease. 

COVID-19 Vaccines in OWS Development
These vaccines were summarized along with the companies participating in OWS-led BARDA and NIH funded Phase 3 efficacy trials. The different platforms used (mRNA, adenoviral vectors, and recombinant protein+adjuvant) were emphasized as a deliberate strategy and, ideally, we will receive licensed vaccines in all three platforms to be used in settings where they will work best. 

SARS-CoV-2 Antibody Landscape (in process)
Antibodies that have moved forward into clinical evaluation were listed and trials status provided.

Emergency Use Authorizations from the U.S. FDA
The emergency use authorizations for COVID-19 therapeutics and vaccines received to date were listed. Noted were the Lilly and Regeneron monoclonal antibodies for the treatment of mild-to-moderate COVID-19 in adult and pediatric patients. Notably, Pfizer has fully enrolled their clinical trial in children down to age 12 so we expect movement in the availability of vaccines for use in this age group.

SBIR Contract Topics

Two re-issued and two new proposed SBIR contract topics for the PHS 2022-1 solicitation were described. The two (previously approved and published) SBIR contract topics to be re-issued are: Point-of-Care HIV Viral Load and Drug Adherence Assays to Accelerate EHE, and Therapeutic Targeting of Intracellular HIV-1 Proteins or Nucleic Acids.

Two new SBIR contract topics were presented for approval:

Topic 1: Novel Platforms for Delivery and/or Expression of HIV Env Immunogens for HIV Vaccines will continue to find new delivery platforms. The power, potency, and safety of using messenger RNA vaccination approaches has been demonstrated by companies such as Moderna and Pfizer. The Division and Networks have been following this work and studies are planned early this year to use such technology for HIV. The objective of this topic is to develop HIV vaccine platforms for delivery of HIV envelope immunogens that induce and can trigger broad neutralizing antibodies (bNAbs) or move along the pathway to trigger bNAbs, and then to demonstrate that the vaccine platforms/immunogens will elicit strong and durable neutralizing envelope responses. Example of Phase I activity includes engineering and fabricating nanoparticle platforms and approaches for delivering existing and/or novel HIV Env immunogens; example of Phase II activity includes developing cGMP manufacturing processes for such nanoparticle formulations.

Topic 2: Genetically Engineered Mice for Pre-Clinical Evaluation of HIV Vaccine Candidates
One current challenge is determining whether a vaccine works and how it can be evaluated. The goal of this project is to utilize genetically engineered mouse models, such as human immunoglobulin knock-in (KI) or other transgenic mice expressing relevant human genes, to accelerate testing and development of HIV vaccine candidates. 

Discussion:

Q: Has there been confirmation from the new administration for the continued support of the Ending the HIV Epidemic (EHE) initiative?

A: There has not been formal confirmation of continuation, but there is no indication that any part of HHS will slow this down and there are signs of expansion. We anticipate a positive outcome as the new Assistant Secretary for Health evaluates everything and discusses with the career staff at HHS. It is one of the reasons that we're moving forward at today’s meeting to propose FY 2022 EHE activities. Although we are presenting these new EHE concepts today at risk, we wanted these EHE funding opportunities to be approved by ARAC should the EHE initiative fall into place.

Q: Can you discuss ACTT and ACTIV differences and activities going forward?

A: ACTT was first out of the gate, and that was run by the NIAID Division of Microbiology and Infectious Diseases, and they conducted the first remdesivir trial, and they evaluated baricitinib, and now they are performing a head-to-head trial with dexamethasone and baricitinib plus remdesivir to see which works better. They have been very focused and very keyed in on answering very specific questions. They are running in parallel and in consultation with ACTIV. ACTT and ACTIV are related, but separate. As far as we know, they are going to continue both of those programs.

Comment:

Re: SBIR Topic 2. Investigators who receive such a contract should be compelled to make any genetically engineered mice that they construct available to the wider academic research community. Getting access to mice is often a stumbling block in carrying out research. This could be very useful, not only for the HIV vaccine field.

ARAC members voted on the two new SBIR contract topics.

SBIR Contract Topic #1: Novel Platforms for Delivery and/or Expression of HIV Env Immunogens for HIV Vaccines

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

SBIR Contract Topic #2: Genetically Engineered Mice for Pre-Clinical Evaluation of HIV Vaccine Candidates

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

Office of AIDS Research Advisory Council (OARAC) Update

Tricia H. Burdo, Ph.D.

Highlights of the 55^th OARAC meeting were presented.

OAR Director’s Report

New OARAC members were introduced, and recent retirements and remembrances were noted.

FY 2021 NIH HIV/AIDS Professional Judgment (PJ) Budget
This document released in August and available online on the OAR website, covers accomplishments in HIV research in FY 2020, a full budget to accelerate clinical research and previews activities for FY 2021 within the context of the four strategic goals outlined in the 2021-2025 strategic plan.

HIV Antiretroviral and Opportunistic Infections (OI) Guidelines Working Groups of OARAC

• These guidelines are posted on the clinical guidelines page at the following website, https://clinicalinfo.hiv.gov/en/guidelines. Documents produced by the panel include caring for patients with HIV in disaster areas, and interim guidance for COVID and HIV.
• OAR staff members met regularly with the working group panels where updates and expectations were discussed.
• OAR is considering the optimal approach for harmonizing and streamlining these panels’ work.

OAR Listening Session Report-Out
Four listening sessions were held in 2020 and feedback from questions asked included the need for more insight on COVID-19 and social justice. More listening events are planned. 

NIH Advisory Council Updates
Reports were presented from each of the three advisory groups: ARAC; National Advisory Council on Drug Abuse (NACDA); and National Advisory Mental Health Council (NAMHC).

OAR Taskforce on COVID-19 and HIV
This group of stakeholders has met several times to bilaterally discuss HIV and COVID issues. The most recent meeting covered COVID and HIV global health issues, updates were given on the related NIH initiatives and programs.

Next OARAC meeting: February 25, 2021 (Virtual Meeting)

Discussion: None

Ending the HIV Epidemic (EHE)

EHE Overview
Ann Namkung Lee, M.P.H.

The background, goal, strategy, and progress of the EHE program was reviewed. The roles of each agency involved in the plan were outlined; for the NIH, it is to inform HHS and partners on evidence-based practices and effectiveness. The NIAID EHE support to date allocated to the NIH Centers for AIDS Research (CFARs) and National Institute of Mental Health (NIMH) AIDS Research Centers (ARCs) for implementation science research was overviewed. The support was for supplemental funding. 

For FY 2022, the plan is to expand on previous efforts and open opportunities for those outside of the CFARs who may be able to reach jurisdictions not reached so far. The EHE concepts to be presented today address the EHE pillars (diagnose, treat, prevent, respond): multidisciplinary treatment approaches, prevention strategies, and epidemiology to end the HIV epidemic. The development process for these three concepts involved collaborations across programs at DAIDS and the NIMH Division of AIDS Research. The writing teams consulted with colleagues at the CDC and HRSA to ensure that the concepts align with, and are coordinated with, their EHE implementation plans. Key principles and next steps were discussed.

Discussion:

Q: Are CFAR supplements anticipated this Spring?

A: For FY 2021 we will have supplements for the CFARs and ARCs again.

Three EHE concepts were presented for ARAC approval.

Multidisciplinary Treatment Approaches to End the HIV Epidemic
Tia Morton, R.N., M.S.N.

This initiative was developed by DAIDS and NIMH DAR staff while considering that HIV viral suppression in the United States is not uniformly achieved in all states and populations. Therefore, research was deemed necessary to yield fresh approaches to healthcare delivery to improve suppression rates by more effectively engaging and retaining populations not suppressed in existing treatment programs. Research funded under this initiative will support the goals of the DIAGNOSE and TREAT pillars of Ending the HIV Epidemic (EHE): A Plan for America by seeking to achieve more rapid and sustained viral suppression and improved outcomes for people living with HIV (PLWH) through better healthcare engagement.

The objective of this initiative is to utilize implementation science to develop, implement and evaluate creative, multidisciplinary approaches to healthcare delivery that more effectively engage and retain populations who are underserved or poorly engaged by current HIV treatment programs.

More local HIV data was discussed for adults and adolescents in the Chicago metropolitan area to highlight the association between poor HIV service delivery and low viral suppression rates. This initiative would allow applicants to focus on such areas in populations with low suppression rates (<30 percent).

Examples of the type of applications sought included: scale specialized clinics that tailor HIV care provision to the needs of individuals who lack consistent care engagement or sustained viral suppression; and prepare and optimize health systems for delivering current and future treatment regimens including long-acting products. A summary of application requirements included a requirement for creative healthcare delivery approaches implemented by multidisciplinary and multisectoral teams (e.g., researchers working in close collaboration with local implementing partners, including city, county, and state public health departments, local and regional clinics and healthcare facilities, clinicians, and community- and faith-based organizations).

ARAC reviewers’ comments for this initiative and the subsequent responses were summarized.

Discussion:

Additional Comments:

• There are patients who literally present every week for their opiate prescription or every week for their voucher, and that has nothing to do with virologic suppression; these vulnerable patients remain unsuppressed. I would emphasize to have viral load suppression as a broad focus treatment goal, and the main thing to achieve in applications for impact on ending the HIV epidemic.
• We agree. Viral suppression is critically important for this population that is difficult to reach. We wanted to be more permissive as an applicant may want to look at engagement and retention in care.

Q: (i) Although this initiative is presented as an R01, are there other opportunities for other mechanisms such as a “K” award to connect to a program like this? (ii) Is there a way of encouraging ethnic minorities as investigators for such a program to avoid potentially missing out on more junior investigators who could contribute here? This might happen if the focus is on “R”s alone.

A: (i) Point taken, it is soliciting a R01 and will take that message back to the writing team. But this is a clinical trial and there are certain mechanisms for that. (ii) Good idea to encourage ethnic minorities. We will have to get back to you with regards on how to do that.

• We think that idea of encouraging minority investigators to apply will be really important, and how we can do that in the context of what is legal is something we struggle with all the time. Will take this under advisement.
• Regarding “K” awards, it is best to talk to the “K” group as an opportunity for them. The “K” career development awards are a separate program and could potentially become a separate focal area.

Additional Comments:

• I appreciate the incorporation of social determinants of health in this RFA and also the structural barriers of access to care.
• It is important that applicants do not use traditional ways to calculate viral suppression rates using the standard kinds of milestones in the HIV treatment cascade. The calculations are often distorted by calculating suppression rates at an early time point. Success may be counted as failure. The key here is linkage and retention that will define success of this kind of initiative.
• When you think about the EHE goals, it really is to achieve virologic suppression for the person and then, of course, for prevention purposes.
• Part of this should be to get access to those people who are not being engaged and retained.
• I think part of this type of program should be to identify those people who are not being retained and figuring out how to bring them in or how to reach them in some way, be it through a mobile clinic or some other modality.
• I think the point is to cast a wide net, which includes ways of bringing individuals into care consistently.

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

Prevention Strategies to End the HIV Epidemic
Dale Burwen, M.D., M.P.H.

This R01 initiative was developed with the NIMH Division of AIDS Research with other NIH ICs as potential partners. Its purpose is to improve the use of evidence-based HIV prevention interventions among populations in jurisdictions identified as highly impacted by HIV. Objectives of the program included supporting research to design and evaluate strategies for reducing HIV incidence among people in the United States at increased risk of infection. The scope of the initiative was summarized which included supporting the goals of the DIAGNOSE and PREVENT pillars of the EHE plan, and the importance was discussed. Examples of research of interest covered differentiated HIV prevention approaches to efficiently deliver evidence-based interventions, and innovative community-based prevention strategies directed toward populations that are at increased risk of HIV infection and are largely unreached by current programs. The reviewers were very supportive of this initiative and their comments were summarized and addressed.

Discussion:

Q: It is exciting to have R01s available to address EHE. A reduction of incidence should be a requirement to reach the EHE goals.

A: We agree that incidence is an important focus and there are possibly three ways for it to be assessed: (i) longitudinal follow-up of individuals, (ii) use of recency algorithms using factors such as CD4 counts and other factors to identify how recent the HIV infection might be and (iii) modeling using the effects found in the study, looking at the prevention intervention and putting that into a model to then see what the effect on incidence would be. The notion of trying to identify measurable decrease in incidence is important.

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

RESPOND: Epidemiology to End the HIV Epidemic
Rosemary G. McKaig, Ph.D.

The objective of this initiative is to respond to underlying changes in the HIV epidemic using cutting-edge epidemiologic methods and data science to enable programs and practices for sustained HIV viral suppression. Another objective is to guide program development and evaluate implementation science interventions to measure success and iteratively plan for next steps. Baseline metrics were discussed and while the overall rates of new HIV infections are slowly declining in the U.S., this needs to dramatically improve to meet EHE goals of a 75 percent reduction in new infections by 2025 and a 90 percent reduction by 2030. To accomplish this, transformative HIV control programs that look beyond what is known and to redirect current thinking and investigations are needed. The opportunity and importance of this initiative were discussed. The scope of work was reviewed and covered: epidemiology to identify key populations, data science to develop novel analytical approaches, and implementation science where assembled multi-disciplinary teams will build robust and rapidly adaptable programs based upon evidence. This initiative supports the RESPOND pillar of the EHE plan. The reviewers of this initiative were fully supportive and enthusiastic about the concept and their comments were summarized and addressed.

Discussion:

Q: How would you visualize the distinctions of an application coming in from a group of investigators from different backgrounds considering the potential overlap in ideas and investigators between this Epidemiology initiative and the EHE Treatment and Prevention initiatives just presented?

A: I would think that the distinctions would be among what the expertise is and where the research questions are. For example, one would hope that we would have epidemiologists who would drive what are the research questions here that are so important, and what do we not know. I think there is a lot of overlap here, but there is a difference in expertise and a difference in the research questions.

Q: There is a need for greater community education and understanding of these new approaches to address any fear, trepidation, and stigma. There is work to be done to help communities better understand the purpose, the function, and how this fits and how it will help us move towards ending the epidemic. It is important to include language in the initiative to recognize these issues.

A: Yes, we can bring in community stakeholders who know the communities better for their advice on the type of data and level of the data, and information to help us to know what is important to this area so we can successfully intervene.

Q: How will the success of these projects be evaluated in the context of potentially multiple overlapping initiatives ongoing in communities? This could lead to success or to false conclusions. Are we disadvantaging some geographic areas where there is not a robust community but where there is great need?

A: As far as the collaboration, we are coordinating our efforts with the CDC and with our partners at HRSA’s HIV/AIDS Bureau so that this research is complementary and offers something unique. The rigorous implementation science approach was thought to be unique by our partners. Ideas are welcome to from the group to help us raise awareness within the less robust communities. We are looking to recruit new applicants all the time.

Q: Considering certain HIV diagnosis data from the CDC are 3 or more years old how do you envision that applicants are going to be able to work with the CDC? For example, we can currently pull CDC data on COVID-19 diagnosis on a daily basis; why can’t we retrieve more current HIV big data from the CDC?

A: This is an important point. We have thought a lot about this problem with the CDC. We do not have the intensity of HIV data from CDC as we currently have with coronavirus. We included the data science component because we have seen, most recently with the pandemic, the tools and ability that the data science colleagues can bring to the field.

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

Programmatic Overview: Key Accomplishments and Future Directions

Therapeutics Research Program
Peter S. Kim, M.D.

The mission of the DAIDS Therapeutics Research Program (TRP) is to improve the health of people living with HIV (PLWH) by developing new and improved therapeutics and diagnostics and advancing associated strategies to achieve durable viral suppression and also ART-free remission. TRP also addresses coinfections and comorbidities with greatest impact on the health of PLWH.

Activities for the TRP are generally weighted towards clinical trials and comprises over 80 active trials or trials in development. An overview was provided of a range of contractual resources that TRP maintains to support these high-quality clinical trials. TRP collaborates with the DAIDS Basic Sciences Program to maintain resources to support the discovery and preclinical development of new therapeutics, now covered under a new ID/IQ contract. In FY 2020 there were 12 funding opportunities with some in collaboration with partners across NIAID and NIH. Six of those opportunities had set-aside funding and ranged from HIV RFAs focused on monoclonal antibodies and self-testing to TB/HIV and TB/HIV diagnostics, hepatitis, and also some critical infrastructure contracts.

Some examples from the TRP portfolio in relation to (i) HIV and HIV-associated comorbidities, (ii) tuberculosis, (iii) hepatitis, and (iv) SARS-CoV-2/COVID-19 were reviewed in more detail.

HIV

The portfolio in this area covers a range of preclinical and clinical studies focused on developing new technologies to improve care. This includes point-of-care and self-testing diagnostics, long-acting treatments that have the potential to attain the ultimate goal to improve outcomes, to empower PLWH and also to simplify care strategies domestically and worldwide. Key points summarized from this area included:

• One research advance of new technology was described that evaluated a lateral flow assay to test the presence of tenofovir for adherence testing.
• Examples of some successes in the preclinical area included two ongoing clinical trials by ACTG (A5357 and A5359).
• Screening for pre-existing resistance is important for evaluating bNAb efficacy in clinical trials, and for eventual clinical use of the antibodies for treatment. There is a need for CLIA-certified assays with rapid turnaround times that are sensitive enough to detect minor resistant variants. We believe that focusing some research on development of diagnostics for rapid detection of bNAb resistance is a future priority that deserves more input.
• The role of TRP in the area of research on HIV comorbidities was summarized and while this area is not directly under the TRP purview, DAIDS collaborates with various NIH ICs to advance different research priorities in these areas.

Tuberculosis (TB)

TB is the leading cause of morbidity and mortality for people living with HIV. Long-term goals include enabling new prevention strategies; developing and testing new diagnostics and treatments for TB/HIV; advancing TB vaccine science; and also advancing clinical and observational research in regions that are most affected by TB/HIV. Key activities summarized from this area included: 

• Advances in the TB drug pipeline that offers us new opportunities to improve treatment outcomes for PLWH that are suffering from TB
• The ACTG 5349/Study 31, a collaboration with the CDC-funded TB Trials Consortium, showed that a four-month regimen that includes high-dose rifapentine and moxifloxacin was as effective as the standard of care
• Host-directed therapies may improve treatment outcomes and enable further shortening of treatment duration; three Phase II POC clinical trials testing potentially promising agents, and also a handful of preclinical research grants are looking at other pathways to see what is possible in this area
• We believe biologics may have significant potential for improving treatment outcomes and we are working to advance therapeutic vaccines for people living with or without HIV
• The Regional Prospective Observational Research in Tuberculosis (RePORT) program which is a consortium of observational cohorts in several countries around the world that have the highest burden of TB (India, Brazil, South Africa, China, Indonesia and the Philippines) with a goal to advance regional and international TB and TB/HIV science and strengthen research capacity and infrastructure

Hepatitis

Focus in this area is on hepatitis B cure and treatment and prevention, and also hepatitis C treatment simplification, including long-acting regimens and improved diagnostics for both HBV and HCV. Key activities summarized from this area: 

• The ACTG 5360 MINMON (minimal monitoring) study tested a minimal intervention strategy for hepatitis C treatment which showed that the regimen was safe and effective in both HCV co-infected and mono-infected patients
• Currently active R21 NOFO supports basic, translational, and clinical research to address the challenges to achieving HBV cure in the presence of HIV/HBV co-infection

SARS-CoV-2/COVID-19

Existing grants and infrastructure were used to supplement a number of investigators to undertake some very important COVID-19 related research with the goal of identifying safe and efficacious therapies for the treatment of SARS-CoV-2/COVID-19. TRP contracts were utilized to support national efforts and impact critical infrastructure needs. 

ACTIV-2/A5401 Trial
This flagship trial co-funded by Operation Warp Speed, Adaptive Platform Treatment Trial for Outpatients with COVID-19 (Adapt Out COVID), to evaluate outpatient treatments for early COVID-19 was designed to be a seamless Phase II to Phase III adaptive trial. Antibodies from Lilly and Brii have been evaluated, and we expect to initiate several other agents into the trial within the next few weeks.

Discussion:

Q: (i) What's your sense of investment into long-acting therapies for TB and hepatitis? (ii) Any thoughts on combined strategies such as polypills or other innovations?

A: For TB, there is a lot that can be beneficial as it can potentially be “got at” with a one-shot or one-time dose for full treatment, unlike HIV. The formulation technology is there but we need to get the small molecules progressing. Input and collaboration with drug company partners is important as they will play a key role.

Q: A TB vaccine working group is ongoing. How will this fit into the TRP work and therapeutic vaccines versus vaccines for prevention?

A: The TB vaccine working group is a collaboration across NIAID along with the other Divisions (DMID and DAIT). The HIV clinical trials networks will play a role because of their dominance in the clinical research field. There's a lot of work to be done, both preclinically and clinically, and it really has been a collaborative effort. I think there's a lot of potential for TB vaccines both in the prevention space and the therapeutic space.

Q: In terms of long-acting drugs, do you think that the NIH will have a role to play with islatravir and lenacapavir, or will it be mainly drug companies at the beginning and then refinements?

A: I don’t have a good sense on these. In general, if a company is willing to take things forward without our input, we're happy with that. The ultimate goal here is to have these treatments be available for clinical use. If and when companies would like our help, of course, then we stand ready to facilitate as much as we can.

Additional Comment:
Regarding partnership: We have had a successful give-and-take collaboration with ViiV on long acting cabotegravir. All along the way there was a commitment to study the right populations, and that was a mutually agreed upon goal. Sometimes the pharmaceutical companies are singled out for criticism, but these partnerships are critical for getting these drugs developed.

Vaccine Research Program
Mary Marovich, M.D.

This overall programmatic update for the Vaccine Research Program (VRP) covered: 

1. Leveraging HIV vaccine research and development for the strategic U.S. government COVID-19 response
2. HIV-1 vaccine discovery and design advances
3. Vaccine concepts in advanced clinical testing
4. Future directions for vaccines

Below is a summary of the key points for each of these areas:

1. Leveraging the HIV Vaccine Enterprise for COVID-19 Vaccine Research
   • The VRP worked on the COVID vaccine development and the monoclonal antibody development. A graphic from the AVAC website illustrated the many different pieces there are to vaccine research, how they fit together, and how a pivot from HIV to COVID research could occur.
   • Vaccine approaches from HIV to COVID-19 vaccine development were summarized which included the AMP study with bNAbs, DNA, chimp and human adenoviral vectors, and mRNA vaccine platforms. These platforms were extensively discussed from a historical perspective.
   • A high-level summary of Phase 3 COVID-19 vaccine candidates and associated studies were presented. This included Moderna’s mRNA platform, Janssen and AstraZeneca’s adenoviral vector platform, and the recombinant protein platforms of Novavax and Sanofi.
   • SARS-CoV-2 mAb prevention portfolio and prevention trials currently being implemented was discussed.
2. HIV Vaccine Discovery and Design Advances
   • Sequential vaccination for bNAb induction will need antibody maturation in humans involving priming diverse bNAb precursors, boosting for affinity maturation, and polishing or finishing using native-like trimers.
   • Previously, a major finding was that recapitulation of HIV-Env co-evolution in NHP was shown to lead to neutralization breadth and this model could be very helpful and informative for bNAb development for humans. Germinal cell approaches were also described as useful for potentially developing a broad B-cell repertoire.
   • Work is being now translated into humans (the VIR-1111, Phase I trial) based on Louis Picker's studies with the CMV-vectors that showed a remarkable ability to clear infection from primates with SIV infection.
   • The IAVI G001, Phase I trial using a 60mer that is adjuvanted with AS01B. This immunogen has been shown to activate precursor pools of VRC01-class IgG-positive B cells.
   • Examples of vaccines being translated from NHP to humans were discussed and covered the BG505 SOSIP immunogen studies in the recent HVTN137 clinical trial.
   • Collaborative HIV Immunogen Project (CHIP) was discussed which has the goal of coordinating immunogen development from NIAID-funded HIV Vaccine Consortia/VRC and other investigators to optimize use of NIAID resources to develop an HIV vaccine that elicits nAbs. A key for this is to do small studies and get answers within a year to make progress.
   • Polishing trimers were listed that are in near term or clinical testing (2020 to 2022) and addressing the need for adjuvants was briefly reviewed. Much progress has been made in funding and accessing adjuvants that can be used throughout the Institute, not just for HIV vaccines.
   • The VRP HIV Env nanoparticle/mRNA portfolio was briefly summarized.
3. Vaccine Concepts in Advanced Clinical Testing
   • The current NIH HIV vaccine strategic plan comprises two pathways: the empirical approach and the theoretical approach. These together with the associated trials were briefly overviewed.
   • Neutralization sieve hypothesis for VRC01 sensitivity testing of AMP breakthrough viruses.
   • Following the AMP study is a triple monoclonal Ab study that is being planned.
4. Future Directions for Vaccines
   • After the early closing of HVTN 702, a viewpoint was written by Dr. Carl Dieffenbach and Dr. Fauci about the need to move forward and how the journey would continue using supporting collaborative cross-disciplinary research, multisector partnerships, and clinical testing of multiple vaccine concepts. The Janssen collaboration which resulted in two efficacy trials was one example given.
   • Efficacy studies of vaccines in clinical trials and their timelines were summarized.

Discussion:

Q: Considering the mRNA success for COVID-19, are there any such mRNA vaccines for HIV?

A: We have been working on this for a while and there are three HIV mRNA vaccine immunogens, which should go into a study probably in June of this year. These are being produced by Moderna. Some mRNAs are also coming out of Duke University.

Additional Comments:

• It's important that we articulate how different these viruses are and why it is not easy to create an HIV vaccine with mRNA.
• The above point is essential. Where RNAs really help us is that they allow quick evaluation of viral envelopes that is going to allow us to potentially save years of testing.

Basic Sciences Program
Diana Finzi, Ph.D.

This overview of the Basic Sciences Program (BSP) covered:

1. Overview of BSP
2. Impact of SARS-CoV-2
3. Highlights
4. Anticipated Priorities
5. Future Directions

Below are the key points from the presentation:

1. Overview of BSP
   • BSP mostly supports early-stage science, specifically the early indications of what might eventually be important breakthroughs. The foundations are in a large number of unsolicited grants, but BSP also solicits grants in order to indicate the direction in areas of particular need. The three branches of the BSP (Pathogenesis and Basic Research, Targeted Interventions and Epidemiology) were described and these comprise approximately 600 grants with an annual budget of $350 million.
2. Impact of SARS-CoV-2
   • Work for periods of this last year has periodically shifted to COVID. Examples of contributions included the following:
     • Helped to move protocols along at the VRC 
     • Helped to create a number of new proposals to the emergency Rapid Acceleration of Diagnostics Programs, the RADx-Tech, RADx-rad, RADx-UP
     • Helped to review emergency NOSIs, emergency NOFOs, supplement requests, ranging in topics from diagnostics to therapeutics, to basic epidemiology, to long-term outcomes
     • Reviewed proposals from thousands of investigators to the NIH, and other agencies such as BARDA
3. Highlights
   • Three examples of the benefits of sustained support from BSP were discussed
     • Reagent Program
       The HIV Reagent Program (formerly AIDS Reagent Program) develops and produces state-of-the-art reagents and then provides those free of charge to qualified investigators throughout the entire world. Also, it served as an example and seed for other repositories. For drug repurposing, there is a ready stock of HIV drugs that could be immediately available upon request to send to coronavirus labs for testing. A new award has just been made to the ATCC that will help maintain this stock of useful, quality-controlled, and up-to-date reagents.
     • CFARs
       Supporting CFARs across the United States in HIV research has been critical in jumpstarting the EHE and informing HHS and partners on evidence-based practices.
     • Basic R01-type studies
       mRNA studies, that represents one example of BSP supported research, was briefly summarized. This covered its therapeutic timeline since its initial discovery in 1961, and the challenge of the immune system to using engineered RNA to instruct cells to make specific therapeutic proteins. This problem was resolved by a grantee in 2006 and this work has led to technologies now being used to effectively combat the COVID pandemic.
4. Anticipated Research Priorities
   • These initiatives covered:
     • Molecular dynamics of HIV
     • Enhancing HIV reservoir susceptibility to elimination
     • Optimizing the anti-HIV CD8+ T-cell response to achieve an HIV cure
     • LITE (Limited Interaction Targeted Epidemiology): Viral Suppression
5. Future Directions
   • The three priorities were listed and more broadly summarized topics covered in the presentation.

Discussion:

Comment: I want to compliment the entire NIAID team and thank them all for their service and for the incredible efforts working on the COVID response while simultaneously continuing the important HIV work.

Q: With the transition to vaccines, how do you see reallocation of effort and time balancing and transitioning, hopefully, what will be less time on COVID to now more basic science for HIV? 

A: We follow what is going on and staying in sync with the grantees and the Division. We are still very much moving ahead with HIV work.

Q: Regarding the effects of COVID on the productivity of junior faculty and investigators who have not been able to be in the lab, can you address this concern and next steps?

A: This is an important issue and we will follow up with the Committee to further address this issue.

Additional Comment:

• It is probably worth thinking through what were the most successful pieces of the response that the Division has had, and which ones maybe were good efforts and not as successful so we can learn from what has happened in the last year.

Prevention Sciences Program
Sheryl Zwerski, DNP, CRNP

The Prevention Sciences Program (PSP) overview covered:

• Background
• Program Orientation
• 2020 Accomplishment Highlights
• What is next?
• Challenges and Opportunities
• COVID Work

The key points from this presentation were:

Program Orientation

• There was a reminder about the global number of people living with HIV, including those newly infected and the number of children, together with the number of AIDS-related deaths.
• The several branches outlined included four branches ranging from the preclinical branch and three clinically focused branches. The others were the administrative core, a registrational trials and a collaborative partnerships team.
• High-level priorities of PSP program included: development of HIV prevention products, improve understanding of the biology of HIV susceptibility, improve engagement of important populations of both women and men, improvement of HIV treatment and prevention in pregnant women and children, optimizing strategies to treat and prevent TB in the maternal and pediatric populations, and evolving the cure research and early HIV testing and detection in infants and children.
• A graphic of the PSP program areas from discovery through clinical testing was presented, including support of three HIV clinical trials networks. The Comprehensive Resources for Topical Microbicides and Biomedical Prevention (CRMP) contract serves as the foundation for all of the other work of the program.

2020 Accomplishment Highlights
These included:

• Completion of the validation of the sheep vaginal safety model, involving creation of an irritation scale, positive and negative controls, and a microbiome inflammation correlate of safety using this model through the CRMP contract.
• Completion of the drug-drug interaction, the metabolism and drug transporter studies in vaginal tissues to support the dapivirine intravaginal ring licensure package.
• Cabotegravir (HPTN 083 & 084) superiority shown from interim analysis, AMP proof of concept studies leading to monoclonal Ab in use for prevention, and completion of placebo rectal douche, rectal insert and suppository study trying to ascertain rectal prevention product preferences.
• Completed enrollment in the dapivirine intravaginal ring MTN 034 study in adolescent girls and young women.
• In partnership with Janssen, regulatory approvals were received for etravirine in the P1090 study for children 2 to 6 years of age, and for maraviroc in the IMPAACT 2007 study for children under 2 years of age. 
• In partnership with ViiV, FDA and EMA approvals were granted for dolutegravir dispersible tablets and film-coated tablets for the youngest children.
• Initiated two studies—Dapivirine intravaginal ring and oral Truvada in pregnant (MTN 042) and breastfeeding women (MTN 043).
• Completion of the IMPAACT 2010 study demonstrated superior safety and virologic efficacy at delivery of the dolutegravir-containing ART regimens in pregnant women, as compared to efavirenz-containing regimens.

What is next in terms of future initiatives?

• Updating the foundation and bridging gaps such as to advance promising next-generation non-vaccine HIV prevention products into human clinical testing, expanding the ethnographic studies that has been worked on through this contract to better understand desire and choice, and how to best engage young women and men in HIV prevention and prevention products.
• Gap-filling resources to support prevention and treatment strategies in maternal and pediatric and adolescent populations, is now being examined with this contract resource, looking at how to support improving age-appropriate formulations for HIV and for TB and other co-infections.
• A focus on TB infection spectrum in children and on having biomarkers that define each of the stages of TB infection in children.

Challenges and Opportunities

• These include cabotegravir LA superiority, oral prep effectiveness with use, and availability of DPV IVR to decrease HIV infection rates in studies.
• The requirement for innovation and community partnership for engaging men and women, and improved insight into decision making around new prevention products.
• Novel ARV-based HIV prevention methods and delivery systems, multipurpose prevention technologies (MPTs), and integrated biomedical and socio-behavioral prevention strategies. Feasibility and cost-effectiveness have to be factored in.
• Maternal and child ART and TB regimens should continue to be optimized.
• Continue to move forward with child-friendlier formulations for HIV and TB treatment and prevention.
• Including pregnant and lactating women in studies earlier in product development is paramount.
• Including adolescents earlier in product development and being sensitive to their needs in planning trial logistics.
• Continued progress towards HIV free remission in youngest populations.

COVID Work

• PSP staff have worked with network and non-network investigators to maintain visit adherence, ensure product provision, timely specimen shipping, and ensure data quality.
• PSP staff have played several other COVID-specific roles involving development and implementation of anti-COVID mAb studies, and participation on COVID review committees for COVID grant funding opportunities and participation on committees at the NIH and HHS level coordinating COVID work.
• PSP staff have contributed on committees focused on COVID in pregnant women and children generally and specifically for children around MIS-C.
• This work with COVID has been done in addition to the ongoing work to advance HIV science.

Discussion:

Comment: I was excited to see the progress including the adolescent population in product development. 

Q: Regarding the EHE presentations that were presented earlier, where does the implementation science fit in with the Prevention Sciences Program when we discuss the priority of combination prevention?

A: Regardless of what we do as far as products and strategies and testing, as we all know, if we can't implement those successfully and at scale, it won’t make much difference. So, it’s very important as far as prevention science is concerned. We have conducted major studies in partnership with CDC, PEPFAR and others who will be the implementers of the products and strategies that we test and put forward. When you look at the Prevention network, implementing the integrated strategy piece is critical. The partnerships are very important to us.

Public Comments:

None.

VI. Adjournment

The meeting of the Council adjourned at 4:32 p.m., on Monday, January 25, 2021.

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

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