NIAID Council Minutes—September 14, 2020

The 196th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened virtually at 10:30 a.m. on Monday, September 14, 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 3:45 p.m. The meeting was closed to the public from 8:00 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
 

NIAID Senior Staff

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

I. Review of Grant Applications

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

Funding Actions: The Council reviewed 5,676 research and training applications with primary assignment to NIAID for a requested amount of $1,829,350,308 in first-year direct costs and recommended approval of 2,353 applications with $736,663,353 in first-year direct costs.

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

Dr. Fauci opened the Council session by welcoming visitors to the meeting. He introduced two Division of Allergy, Immunology, and Transplantation (DAIT) ex officio members: Dr. John Wherry, chair of the Department of Systems Pharmacology and Translational Therapeutics, and director of the Institute for Immunology at the University of Pennsylvania; and Dr. James Crowe, Jr., director of the Vanderbilt Vaccine Center, and professor of Pediatrics and Pathology, Microbiology and Immunology at Vanderbilt University.

Dr. Fauci acknowledged the contributions of three retiring Council members: Drs. Mark Feinberg, Stanley Lemon, and Robin Patel. He thanked Dr. Eugene McCray for his long-standing service as an ex officio member of the AIDS Research Advisory Committee and his dedication to serving people living with HIV. Dr. McCray is retiring as director of CDC’s Division of HIV/AIDS Prevention.

Consideration of Minutes of Previous Meeting

Council considered the minutes of the June 1, 2020 meeting and concepts that had been presented and approved them.

Appointments and Organizational Changes

Dr. Fauci announced the appointment of several new NIH institute directors.

Dr. Lindsey Criswell has been chosen as director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She will succeed that Institute’s long-time director, Dr. Stephen Katz, who passed away suddenly in December 2018.

Dr. Michael Chiang has been selected as the new director of the National Eye Institute.

Dr. Rena D’Souza has been named the new director of the National Institute of Dental and Craniofacial Research, a position she will assume later this year.

Dr. Rick Woychik is the new director of the National Institute of Environmental Health Sciences (NIEHS), located in Research Triangle Park, North Carolina. He had been serving as acting NIEHS director since October 2019.

Dr. Shannon Zenk has been chosen to head the National Institute of Nursing Research.

NIAID’s Division of Intramural Research (DIR) has two new laboratory chiefs. Dr. Yasmine Belkaid has been named chief of the new Laboratory of Host Immunity and Microbiome, and Dr. Pamela Guerrerio has been chosen as chief of the Laboratory of Allergic Diseases to fill the vacancy following the departure of Dr. Joshua Milner.

NIAID’s Division of Clinical Research (DCR) selected two new branch chiefs. Greg Gendron is the new chief of the Program Planning and Analysis Branch, and Suzanne Spisso is chief of the DCR Intramural Clinical Management and Operations Branch.

Dr. Surekha Vathyam has joined NIAID as the deputy director of the Technology Transfer and Intellectual Property Office.

Tributes and Awards

Dr. Fauci paid tribute to Dr. Uli Siebenlist who passed away in August. He was the founding chief of the Immune Activation Section in NIAID’s Laboratory of Immunoregulation. Dr. Siebenlist made many seminal contributions to the field of molecular immunology.

Budget Update

Dr. Fauci began by summarizing the President’s budget request for fiscal year (FY) 2021, which proposed a decrease of 7 percent for NIH, or $2.9 billion below the FY 2020 enacted level. Most institutes received reductions of 8 to 9 percent. NIAID’s budget would remain flat from FY 2020 to ensure that the Institute has necessary resources to continue critical basic and applied research on COVID-19 and other infectious diseases.

The Senate continues to mark up an FY 2021 budget. The House passed a spending package proposal in July that provides NIH with a $5.5 billion increase over the FY 2020 enacted amount, which brings the NIH budget to $47.2 billion. Included in that amount is $5 billion—available until FY 2025—in emergency funding to help current grantees recover from COVID-19-related delays in their research.

NIH would receive an overall increase of 13.3 percent, with most institutes receiving 7.3 percent increases. NIAID’s budget would increase by 8.6 percent, which includes $40 million for research on a universal influenza vaccine and a $10 million increase to the Institute’s Centers for AIDS Research.

NIH will start FY 2021 under a continuing resolution.

Dr. Fauci presented NIAID’s interim FY 2021 financial management plan. Taking a conservative funding approach, our interim R01 payline will be the 10th percentile for non-new investigators and the 14th percentile for new investigators. NIAID does not plan to make programmatic cuts to noncompeting and competing grants. Competing research initiatives will be cut up to 20 percent from their planned budget levels. Our estimated success rates for research project grants will be between 19 and 22 percent.

Through the Coronavirus Aid, Relief, and Economic Security (CARES) Act and the Coronavirus Preparedness and Response Supplemental Appropriations Act, NIAID received $1.5 billion in supplemental funding, which is available until the end of September 2024.

NIAID has provided $670 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, and $223 million has been allocated to address infrastructure needs at NIAID’s Vaccine Research Center in Bethesda and Rocky Mountain Laboratories in Hamilton, Montana.

HHS provided NIAID with $767 million from the CARES Act to support Operation Warp Speed-endorsed clinical trials of vaccines and therapeutics. 

Legislative Update

On June 23, Dr. Fauci testified before the House Energy and Commerce Committee on NIH’s role in addressing the public health and scientific challenges of COVID-19. He updated the Committee on NIH’s progress developing diagnostics, therapeutics, and vaccines for COVID-19, and highlighted the encouraging preliminary results on the efficacy of remdesivir for treating severe COVID-19.

Dr. Fauci testified before the Senate Health, Education, Labor, and Pensions Committee on June 30. He briefed the Committee on efforts to safely return children to in-person schooling and NIH’s efforts to ensure the diagnostics, therapeutics, and vaccines being developed will be available to minority communities disproportionately affected by the pandemic.

On July 31, Dr. Fauci testified before the House Select Subcommittee on the Coronavirus Crisis to update members of Congress on the many advances achieved by NIAID-supported COVID-19 research.

On July 23 and September 3, Dr. Fauci joined NIH Director Dr. Francis Collins to speak with the Congressional Black, Hispanic, Asian Pacific American, and Native American Caucuses about NIH’s efforts through the COVID-19 Prevention Network to encourage members of minority populations to enroll in COVID-19 research.

Over the last several months, Dr. Fauci briefed senators and members of the House of Representatives on various topics related to NIAID’s COVID-19 research response. He 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 HIV/AIDS from UNAIDS. In 2019, 38 million people were living with HIV, and there were 1.7 million new infections and close to 700,000 deaths from AIDS-related illnesses. In July, the International AIDS Society successfully held a virtual COVID-19 conference.

Dr. Fauci then continued with a COVID-19 update. His schedule has included participating in numerous COVID-19 public health forums, media interviews, fireside chats, and popular social media appearances.

He summarized the number of COVID-19 cases and deaths globally and in the United States. As of September 9, 2020, there were about 28 million cases and 1 million deaths globally, with more than 6 million of those cases and about 190,000 deaths in the United States.

Dr. Fauci provided information on manifestations of severe COVID-19 disease, multisystem inflammatory syndrome in children, lingering problems in those with symptomatic disease, populations at increased risk for severe COVID-19 illness, and the racial and ethnic disparities that have been observed most notably among African Americans, Latinos, American Indian, Alaska Native, and Pacific Islander populations.

NIAID prepared and published a Strategic Plan for COVID-19 Research in April. It covers fundamental basic knowledge of pathogenesis and viral biology, development of diagnostics and assays, characterization and testing of therapeutics, and development of safe and effective vaccines.

Dr. Fauci concluded with an update on the various COVID-19 diagnostic tests that are available; therapeutics that are under investigation and those that have been recommended by the NIH COVID-19 Treatment Guidelines Panel; and vaccine candidates.

III. Guest Speaker—Steven M. Holland, M.D., director, Division of Intramural Research, NIAID

Dr. Holland began by giving an overview of the DIR’s activities over the last year, which include 699 publications and about 200 ongoing clinical studies. COVID-19 funding allowed DIR to initiate 173 new projects, which resulted in 98 published COVID papers.

He reviewed DIR’s priorities, which are:

  • Transformative medicine and biomedical research
  • Bench-to-bedside research taking advantage of NIH’s Clinical Center, as well as domestic and international clinical sites
  • Responding to public health threats, including drug-resistant microbes, emerging viruses, and needed vaccines
  • Partnering to advance vaccines, therapeutics, and diagnostics for infectious and immunologic diseases

Dr. Holland also paid tribute to Dr. Uli Siebenlist, an outstanding investigator in DIR who passed away in August. He mentioned DIR leadership changes that have occurred over the last year, along with personnel changes, including retirements, new lab chiefs, new hires, recently tenured investigators, and new tenure-track investigators.

The NIH Equity Committee has developed plans to limit laboratory chiefs to three full terms of four years each, with review after each term. Exceptions are possible. Plans will be developed for those lab chiefs who are already over 12 years.

Dr. Holland announced recent honors received by DIR staff, including the following: Dr. Gigi Notarangelo was elected to the National Academy of Medicine; Dr. Mike Lenardo was elected to the National Academy of Medicine and the UK Academy of Medical Sciences, and received the American Association of Immunologists (AAI) 2020 Career Achievement Award; Dr. Susan Pierce received the AAI 2020 Career Achievement Award; Drs. Yasmine Belkaid and Tom Wellems were elected to the American Academy of Arts and Sciences; Dr. Tom Nutman received the American Society of Tropical Medicine and Hygiene Ben Kean Medal; Dr. Peter Williamson was elected to the Association of American Physicians; Dr. Mihalis Lionakis was elected to the American Society for Clinical Investigation; and Dr. Bernard Moss was awarded the American Society for Microbiology Lifetime Achievement Award.

Dr. Holland mentioned the joint initiative between NIAID, the National Cancer Institute, and the National Heart, Lung, and Blood Institute, around the issues of bone marrow transplantation and cellular and gene therapy, which encourages collaboration and co-focus of institute staff on the same set of patients. In November, Dr. Sung-Yun Pai will come to NIH from Boston Children’s Hospital to lead the program.

He concluded by highlighting some of DIR’s scientific research on the microbiome, Ebola vaccine, vaccine responsiveness, mosquito cellular immunity, and SARS-CoV-2.

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

Dr. Rotrosen welcomed the subcommittee members to the 196th meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting. 

Dr. Rotrosen presented the following scientific and Division activities:

Staff and Organizational Changes

Steve Sigelman, R.N. In July 2020, after more than 11 years of service to the Division, Mr. Sigelman retired from the position of nurse consultant/project manager in the Asthma and Airway Biology Section of the Allergy, Asthma and Airway Biology Branch, DAIT/NIAID. Mr. Sigelman made important contributions to extramural clinical research, especially with respect to the Inner-City Asthma Consortium.

Karina Allbritton. In May 2020, Ms. Allbritton was promoted to the position of supervisory public health analyst, Program Operations Unit, Office of Program Planning, Operations, and Scientific Information (OPPOSI). She graduated from Hampton University with a B.A. in English Arts in 1999. After four years in the business world, she joined OPPOSI as a program analyst in 2003, where she became highly skilled in the areas of grants management, initiative development, budget management, and Council preparation.

Adelina Bartels, M.H.A. In May 2020, Ms. Bartels was promoted to the position of supervisory public health analyst, Communications, Policy and Legislation Unit, OPPOSI. She graduated from Howard University in 2007 with a B.Sc. in Health Science Management, and later obtained an M.H.A. in Health Systems Management from George Mason in 2013. In 2004, she joined the National Center for Complementary and Integrative Health and in 2007 she became a program coordinator for the Substance Abuse and Mental Health Services Administration. In 2008, she joined DAIT’s Office of Regulatory Affairs, eventually becoming the contract officer representative for the Regularity Management Center.

Monica Zamisch, Ph.D. Dr. Zamisch joined the Transplantation Branch in August 2020, as a program officer in the Transplantation Basic Sciences Section. Dr. Zamisch received her Ph.D. in immunology in 2005, from the University of Texas at Houston-MD Anderson Cancer Center. After a postdoctoral fellowship at NCI in the Laboratory of Immune Cell Biology, she enjoyed a brief fellowship at the FDA in the Division of Viral Products, CBER, before joining DARPA as a senior scientist program lead for the Defense Sciences Office and the Biological Technologies Office. Dr. Zamisch’s expertise in immune cell development, which includes the study of molecular networks, histology and microscopy, as well as her extensive experience in program development, management, and review across multidisciplinary fields brings added value to our team.

Division Activities

Allergy, Asthma, and Airway Biology Branch

From Bench to Bedside: Potential Therapeutics for Allergic Diseases From the NIAID-Supported Asthma and Allergic Diseases Cooperative Research Centers. NIAID organized the above sister society symposium as part of the annual meeting of the European Academy of Allergy and Clinical Immunology (EAACI). The symposium was held virtually on June 6, 2020. Three Asthma and Allergic Disease Cooperative Research Center (AADCRC) principal investigators (PIs) were featured. They presented lectures on topics including targeting Rhinovirus for asthma prevention, the utility of Glucagon-like-1 receptor agonists in asthma, and therapeutic opportunities of Sialic acid-binding immunoglobulin-type lectins (Siglecs).

Basic Immunology Branch

Collaborative Influenza Vaccine Innovation Centers (CIVICs) First Annual Program Progress Meeting. On August 18 and 19, 2020, NIAID hosted the first annual meeting of the CIVICs investigators via a web-based platform. The purpose of the CIVICs contract program, which is jointly managed by DAIT and DMID, is to develop improved influenza vaccines that are both efficacious and broadly protective, as outlined in NIAID’s universal influenza vaccine strategic plan. The CIVICs program is generating novel vaccine candidates, performing preclinical testing and validation of candidates, and manufacturing and testing candidate vaccines in clinical trials, including human challenge studies. Detailed immunologic analyses are being conducted on the preclinical and clinical samples to further improve the vaccines and identify correlates of immune protection. Data from the program is being managed by a statistical and data management coordination center. The meeting enabled the PIs to describe recent progress and continue developing collaborations initiated in the first year of funding.

Autoimmunity and Mucosal Immunology Branch

Efforts on SARS-CoV-2 Related Multi-system Inflammatory Syndrome in Children (MIS-C). As part of the NIH response to the COVID-19 pandemic, the Division of Allergy, Immunology, and Transplantation of NIAID sponsored a workshop entitled, “The Immune Roadmap to Understanding MIS-C”, on Wednesday, June 24, 2020. Expert immunologists and clinicians discussed the putative role of B cells, T cells, innate immunity, genetics, epigenetics, and other immunologic pathways in the pathogenesis of MIS-C, and made specific recommendations for studying these pathways in the context of clinical studies and trials. The workshop was well received, with over 400 attendees. A workshop report has been submitted to Nature Medicine.

In addition, NIAID is collaborating in a trans-NIH effort, led by Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Heart, Lung, and Blood Institute, to study MIS-C. The NIAID-led portion of this effort will consist of a multi-site consortium of pediatric subspecialists and immunologists who will conduct a prospective, multicenter, observational cohort study of children with MIS-C, with a focus on immunologic mechanisms and immune signatures associated with different phenotypes of disease presentation. Enrollment is expected to begin early in the fourth quarter of 2020.

These efforts have been developed collaboratively between the Autoimmune and Mucosal Immunology Branch and the Transplantation Branch.

Mucosal Immunology Studies Team (MIST). From June 15 to 17, 2020, the annual meeting of the MIST cooperative agreement research program was held as a virtual meeting. MIST is composed of 14 U01 cooperative agreement awardees who focus on discovery of novel immune mechanisms, cells, mediators, and pathways operating at the mucosal surface; exploration of innovative hypotheses; and tackling difficult unsolved questions in mucosal immunity. MIST awardees presented their progress and discussed all the projects, new ideas and tools progress on their projects, provide constructive advice on ongoing projects, facilitate sharing of ideas and of newly developed tools, and develop new collaborations. The meeting provided awardees of the MIST Scholar Award the opportunity to present progress on their pilot projects, and receive feedback and advice for MIST members.

Autoimmune Disease Coordinating Committee (ADCC). On May 29, 2020, NIAID convened a celiac disease-focused virtual ADCC meeting to discuss current NIH activities in celiac disease, as well as needs and gaps in research. The meeting was attended by over 80 participants including NIH members of the ADCC, representatives from autoimmune disease advocacy, and professional organizations. Invited experts addressed multiple areas of research opportunities including the unmet needs in celiac disease (Marilyn Geller, CEO Celiac Disease Foundation), unmet needs and opportunities in basic research (Dr. Bana Jabri, professor of pediatrics, University of Chicago), clinical and translational research needs and gaps (Dr. Joseph Murray, professor of medicine, The Mayo Clinic), and the non-dietary therapeutics pipeline (Dr. Ciarán P. Kelly, professor of medicine, Harvard Medical School). Additional presentations focused on the prevalence of autoimmune disease, and celiac disease findings from the National Institute of Digestive Disease and Kidney Institute-supported “Environmental Determinants of Diabetes in the Young” study.

Radiation and Nuclear Countermeasures Program

Biomarkers in Radiation Countermeasures and Biodosimetry Workshop. On June 1, 2020, a workshop led by NIAID in partnership with the Biomedical Advanced Research and Development Authority (BARDA), was held as a virtual meeting. Topics included presentations and discussions on biomarkers in the biodosimetry framework, biomarkers in the medical countermeasures setting, and transitioning biomarkers from the model to clinical setting. Many prominent researchers from the United States and Europe presented their work with biomarkers. Representatives from the FDA also spoke about regulatory considerations for seeking qualification of biomarkers, and clearance of biodosimetry devices generally as radiation diagnostics. Discussions of existing gaps in the field, challenges, and the need for real-world applications of the research were held throughout the workshop, and a meeting report will be published to share the information generated by the workshop with the wider scientific community.

Animal Care in Radiation Medical Countermeasures Studies Workshop. On August 25 and 26, 2020, a workshop sponsored by NIAID was held as a virtual meeting, with planning input from BARDA colleagues. Small and large animal models of total body- and partial body-irradiation were presented, and panel discussions covered a wide range of topics, including animal handling and housing; hydration and diet; infection control and other standards of care; euthanasia criteria; IACUC interactions; and statistical considerations. The benefits of and obstacles to harmonizing animal models also were considered. The discussion was lively and informative with helpful takeaway points for all radiation medical countermeasures researchers. An overview meeting report is planned for publication in Radiation Research.

Division Advisory Council Presentation Concept Review

FY 2022 Research Concept Clearances

Human Immunology Project Consortium (HIPC) (U19, Clinical Trial Not Allowed) and Human Immunology Project Consortium (HIPC) - Coordinating Center (U01, Clinical Trial Not Allowed)

These initiatives will support the continuation and expansion of NIAID’s Human Immunology Project Consortium (HIPC), which is designed to characterize human immune responses at steady-state and in response to perturbations, such as pathogenic infections, vaccinations, and immune-mediated diseases or their treatments.

The subcommittee endorsed and unanimously approved the two initiatives.

The Immunology Database and Analysis Portal (ImmPort)

The objectives of the ImmPort initiative are 1) to support the maintenance and improvement of the ImmPort data repository, which hosts data primarily from a select set of NIAID’s research studies and shares the hosted data with the research community, and 2) the transformation of the shared data into a user-friendly resource to enable reuse of the data to gain new insights and findings to advance immunology research.

The subcommittee endorsed and unanimously approved this initiative.

FY 2023 Research Concept Clearances

Nonhuman Primate Transplantation Tolerance Cooperative Study Group (U01, U19 Clinical Trial Not Allowed)

The goals of the NHPCSG, a multi-institution consortium, are to identify and develop novel therapeutic regimens for donor-specific tolerance induction, refine existing regimens, evaluate preclinical efficacy of candidate regimens, and elucidate the underlying mechanisms responsible for the induction, maintenance, and/or loss of tolerance in NHP organ and islet transplant models.

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

Dr. Emily Erbelding, director of the Division of Microbiology and Infectious Diseases (DMID), chaired the NIAID Microbiology and Infectious Diseases Council Subcommittee meeting on September 14, 2020. She provided a DMID personnel update, recognizing new staff appointments made in the Division since the last Council meeting, including Candice Beaubien and Julie Dyall, Virology Branch; Maryam Jahromi, Office of Clinical Research Resources; and Julio Aliberti, Parasitology and International Programs Branch. She also noted the addition of two AAAS Fellows who are currently rotating with DMID: Erica Bizzell, Bacteriology and Mycology Branch, and Eleanore Chuang, Enteric and Sexually Transmitted Infections Branch.

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

  • Establishment of the Centers for Research in Emerging Infectious Diseases, a new DMID-supported global network that will conduct multidisciplinary investigations into how and where viruses and other pathogens can emerge from wildlife and spillover to cause disease in people.
  • Award to develop an inactivated viral particle vaccine against enterovirus D68, a suspected cause of acute flaccid myelitis.
  • Update on the NIH Antimicrobial Resistance Diagnostic Challenge prize, which NIAID and BARDA have helped support, noting that a final prize was recently awarded to a company that has been supported by DMID to develop other related devices.

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

Dr. Cassetti began her presentation with a brief overview of how lessons learned from the Zika virus outbreak that began in 2015 informed DMID’s initial response to the novel coronavirus identified in 2019. Early activities spanned requests for supplements to ongoing projects, the issuance of rapid funding opportunity announcements and several notices of special interest, and an amendment to an active broad agency announcement to incorporate relevant COVID-19 topics. She also described several preclinical activities initiated to jump start research on this novel pathogen, many of which were supported through the suite of preclinical service (PCS) programs supported by DMID. Examples include the development of animal models to understand the pathogenesis of this new virus as well as to guide decisions regarding evaluation and down-selection of candidate vaccines and therapeutics; implementation of sequencing studies to understand the origin of SARS-CoV-2 as well as the evolution of the virus throughout the epidemic thus far; collection and development of reagents for distribution to the scientific community, mainly through the BEI Resources Repository; support of serology studies in collaboration with NCI and CDC; initiation of natural history studies to better understand transmission among household members, mothers and infants, and health care workers; initiation of in vitro screening studies and other efforts to advance the development of promising therapeutic candidates or to evaluate the potential to repurpose existing products; and design and implementation of a variety of studies through the vaccine testing and manufacturing PCS programs, including toxicology studies and vaccine efficacy studies in a nonhuman primate model.

Dr. Erbelding described ongoing clinical activities, updating Subcommittee members on vaccine and therapeutic efforts. She noted that Operation Warp Speed (OWS) was initiated by the Administration to accelerate progress in developing efficacious vaccines, effective diagnostics, and promising therapeutics for COVID-19. She described the newly formed COVID-19 Prevention Network, which brings together expertise from four networks supported by the Division of AIDS and DMID and their global partners. She identified several vaccines that have launched into efficacy trials, noting that most are being conducted under the auspices of OWS. In addition, she described the various vaccine candidates under development and noted their status along the product development pathway. She also noted a recent National Academies of Science, Engineering, and Medicine report that presents proposed phased implementation groups for vaccine administration, once a vaccine becomes available in the United States. She discussed the need to evaluate these vaccines in special populations, including children and the elderly. She also discussed ongoing therapeutics efforts, notably the Adaptive COVID-19 Treatment Trials (ACTT); the third iteration of the study is currently ongoing. She also announced plans to launch the Big Effect Trial, which will evaluate candidate drugs that appear promising but lack enough data to move into a big efficacy trial, such as ACTT.

Importantly, both Dr. Erbelding and Dr. Cassetti noted ongoing collaborations with colleagues throughout the Federal government, notably with the Biomedical Advanced Research and Development Authority (BARDA) within the Office of the Assistant Secretary for Preparedness and Response and with colleagues associated with OWS, to advance many of these efforts.

FY 2022 Concepts Presented for Clearance

Innovation for Tuberculosis Vaccine Discovery

The Subcommittee members were supportive of this concept, which would support the development of novel tuberculosis (TB) vaccine approaches. They considered it to be a timely, much needed, and high-priority research topic. They acknowledged that there is a compelling need to attract creative ideas for the development of novel TB vaccine candidates and to expand and diversify the current, somewhat narrow TB vaccine pipeline. Subcommittee members recognized the opportunity to build on recent promising preclinical and clinical advances in the TB vaccine field. They considered the proposed two-stage grant mechanism appropriate for the high-risk, innovative approach which is also expected to encourage participation of investigators new to the TB vaccine field. Subcommittee members cautioned that there may be limited national BSL-3 capacity to conduct TB vaccine challenge studies in the various animal models, especially in nonhuman primates. NIAID noted that the preclinical services the Institute provides to the community may be leveraged and that the proposed concept complements current NIAID efforts, including those conducted through the Immune Mechanisms of Protection Against Mycobacterium tuberculosis (IMPAc-TB) Centers. Subcommittee members recommended that an annual meeting with funded investigators could be beneficial. They emphasized that NIAID is a global leader supporting the development of novel TB vaccine candidates and encouraged NIAID to expand collaborations with other funders. The concept was unanimously approved.

Basic Research To Inform Vaccine and Therapeutic Development for Non-Polio Human Enteroviruses (NPEV)

The Subcommittee members were positive about the objective of this concept, which is to expand basic research on non-polio enteroviruses (NPEV) to inform the development of broad-spectrum antivirals and vaccines for NPEV, a group of pathogens that has a significant impact on public health but for which research has been limited. Subcommittee members recognized that research toward developing broad spectrum countermeasures is critical because NPEV are too numerous to develop vaccines or therapeutics against each of the more than 100 strains. While recognizing the difficulty in identifying broadly neutralizing antibodies against NPEV, the Subcommittee members consider it to be a worthwhile effort. The Subcommittee members also recognized that this initiative could invigorate the enterovirus research community, which has been reduced in size in recent years. Additionally, subsequent NPEV research advances may also inform the development of countermeasures against rhinoviruses, which are known to induce asthma exacerbations and are also without effective therapeutics or vaccines. Finally, the Subcommittee members recommended that the concept focus on research activities that will inform both vaccine and therapeutic development. The concept was unanimously approved.

Syphilis Specimen Repository

Subcommittee members were supportive of this concept, which would establish a program to collect high-quality human specimens and relevant clinical data to aid the needs of developers of syphilis diagnostic technologies. The concept was considered important, timely and needed to help inform diagnostic development. The members appreciated that current methods to diagnose syphilis are antiquated, complex and delay diagnosis, and that there is a clear need to spur development of diagnostics that would be more definitive, easy to use, and implement. Members stressed that it will be critical to leverage existing NIAID infrastructure to house the specimens rather than using funds to create a repository de novo. Members also highlighted the need to maximize sample collection and that this may require focusing on one or perhaps two stages of syphilis. Discussion also focused on ensuring diversity in the patient population with respect to race/ethnicity and geography, and inclusion of special populations and those with comorbidities, especially other sexually transmitted infections like HIV. The concept was unanimously approved.

Early Phase Clinical Trials Units

This concept would establish clinical trial units to advance candidate countermeasures through the product development pathway. The assigned Subcommittee reviewers expressed interest in the scope and accomplishments of the current program, which they consider valuable. The differences between the current program and its proposed improvements were delineated, and program staff described examples of how products evaluated in Phase 1 trials had moved into further development in Phase 2 and 3 trials both sponsored by NIH and via industry partners using other mechanisms. Subcommittee members inquired about whether NIAID clinical support services available to the program; it was clarified that a number of NIAID’s contracts (e.g., data management, product storage and distribution, regulatory filing and support) would be available to support studies conducted through this program. Finally, a Subcommittee member suggested that Phase 1 trials and special populations be prioritized; it was confirmed that this would remain the focus of the program. The concept was unanimously approved.

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

Dr. Dieffenbach recognized the upcoming retirement of ARAC ex-officio member, Dr. Eugene McCray, the current director of the Division of HIV/AIDS Prevention at the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STDs, and HIV Prevention. Three members rotating off the Committee were recognized and thanked for their service: Drs. Betsy McFarland, Paul Bieniasz, and Richard Chaisson.

Budget Update

A table representing the President’s budget submitted in February 2020 to Congress for FY 2021 was summarized. Although there was an overall 7 percent decrease proposed for NIH, there was no decrease in funding proposed for NIAID. Additionally, the House passed a spending proposal on July 31 that provided emergency relief funding for current grantees to recover from COVID-19 delays in addition to nominal increases for annual research. The Senate spending proposal is in progress and FY 2021 is expected to begin under a continuing resolution (CR). Under a CR, the fiscal year will start under a constrained financial management plan: Interim R01 paylines would be held to 10th percentile for established PIs and 14th percentile for new PIs. NIAID maintains no programmatic adjustments to noncompeting and competing awards. DAIDS will likely shave funding for competing research initiatives. Under a CR, we expect to maintain a success rate between 19 and 22 percent. If there is an approved budget, there is a possibility that paylines might increase, and the estimated success rates would then increase as well.

NIAID COVID-19 Emergency Supplemental Budget

A summary was provided of the supplemental budget appropriations totaling about $1.5 billion received this year to support coronavirus research. These funds were divided into categories of basic research, diagnostics, therapeutics, vaccines, and infrastructure work. An estimated budget as of August 2020 for the research areas was presented. The funds are being expended based on priorities and based on scientific opportunity. Unlike the usual appropriated funding, the COVID-19 emergency supplemental dollars are multiyear funds that do not need to be expended in a given fiscal year; these supplemental funds may be expended within a four or five-year timeframe. Congress will decide on future coronavirus disease research funding depending on how the epidemic continues.

In addition to the funding that we've received through direct appropriations, we were allocated money for Phase 2/3 clinical trials in the areas of vaccines and therapeutics through collaboration with BARDA and Operation Warp Speed (OWS). The budget displayed for these large studies is not a final budget, as intended vaccine studies scheduled to open this Fall are not included.

Discussion:

Q: Congress has appropriated a certain amount of funding for HIV research; how does another infectious disease pandemic affect the HIV budget?

A: At the outset of the pandemic there was a suspension of most research activities at the university level unless you were working on coronavirus. Although the idea is to keep a focus on HIV, there was some flexibility to allow HIV money to be used to jumpstart coronavirus work. Subsequently, bona fide coronavirus projects received coronavirus funding. For example, in the AIDS Clinical Trials Group, everything that they're doing related to coronavirus disease is being paid for with coronavirus dollars.

Q: Are paylines for K grants set at this time like the R01s?

A: The “K” paylines tend to get set later in the year when there is a full budget allocation.

Q: Many scientists’ labs have pivoted toward hybrid research that includes some HIV research and some coronavirus research. Regarding R01 renewals, should labs separate work that is being done on HIV and COVID in their grant applications?

A: This has not been worked out yet but will be discussed with NIAID leadership and a position statement may be crafted. Because of our structure at NIAID with two separate Divisions, for HIV (DAIDS) and other infectious diseases (DMID), it may make sense to complete two grant applications. If there are shared (hybrid) research projects, an appropriate study section would need to be identified.

Q: Has NIH decided how the new budget will be allocated between different research areas e.g., COVID vs. HIV vs. other microbiology?

A: The HIV budget is submitted by the NIH Office of AIDS Research (OAR); they look across the NIH and assemble the budget for AIDS, and then we get a portion of that. Every year there is a specific carve-out of the NIAID budget that is set aside for HIV. The breakdowns between tuberculosis (TB), other bacterial and viral diseases, immunology, allergy, intramural research, etc. is also dictated by Congress. There is currently no coronavirus appropriation and the supplemental funding will continue to be spent for the foreseeable future. Whether coronavirus research has to compete with everything else is a question that will have to be dealt with in the next year or two.

Q: Without the full appropriation under a continuing resolution, how do you handle the funding for the upcoming renewal of a large enterprise like the HIV/AIDS Networks and CTUs?

A: Under a CR, grantees will receive a partial award to start. Over the year, spending will be tracked, and appropriate adjustments will be made to make awardees whole.

NIAID “K” Awards: Subsequent Grant Award Rates

A question came up at the January ARAC meeting about the success rate of K awardees competing for R01s, and whether NIAID had any data on the success rates. NIAID data of past awards (FY 2009 to 2014) showed that 81 percent of DAIDS K awardees successfully competed for a subsequent RPG, and 61 percent were awarded a subsequent R01. Only 10 percent of DAIDS K awardees never applied for a subsequent award. DAIDS K awardees included more MDs than other degree holders. These data will be followed, updated, and presented to the ARAC in the future.

Discussion:

Q: Are there any plans to look at these data with respect to sex or race?

A: This is important and we can go back and look at that in aggregate. Moving forward, it is critical to address racial disparities and continue to maintain a gender balance at all levels of funding.

Additional Comments:

  • These data are really positive and contain important information. These data should be formalized and shared.
  • There is a concern that the latest data are only from 2014 and it would be preferred to obtain more recent data before making any definitive conclusions.

DAIDS COVID-19 Activities

A summary highlighting some of the current coronavirus research activities was presented. This covered the start dates for the vaccine companies participating in the OWS-led BARDA and NIH-funded Phase 3 efficacy trials. Also discussed was the SARS-CoV-2 monoclonal antibody (mAb) landscape, which included both treatment and prevention protocols. An overview was presented of ACTIV-2, a platform trial for outpatient treatment with monoclonal antibodies and direct acting antiviral drugs. This trial is being supported by OWS. Agents entering the study start as a Phase 2 and when one of those agents meet pre-specified criteria, the study can transition to Phase 3. When two or more agents are being tested concurrently, there is a shared placebo group. The current challenge is recruiting volunteers who are diagnosed with mild or moderate coronavirus disease and enrolling them quickly in the study for infusion as soon as they are identified as positive. The HIV research community is very aware of the “test and treat” concept and this same practice applies for coronavirus treatment. Diagnosis and treatment are needed as quickly as possible in order to make a difference in terms of understanding the biology of coronavirus disease and how highly potent antivirals could mitigate downstream disease. If you have a testing facility at your institution, see what you can do to make sure that it is linked to an infusion center to expedite these treatment trials.

Comment: It is critically important that the COVID-19 studies be allowed to evolve to scientific conclusion based on evidence for public health reasons, for integrity in the process, and for humanity.

Discussion:

Q: Is there a distinction between ACTIV and some other studies (they seem similar and can be confusing), specifically the ACTIV-2 and the ACTG monoclonal program?

A: ACTIV-2 and ACTG monoclonal program are the same. An area of emphasis at NIAID is to improve coordination and share information between trial groups to improve any confusion.

Q: Are there any trials of antibodies as prophylaxis?

A: Yes. Those trials are being run by the Coronavirus Prevention Network (CoVPN) and both the Regeneron and Lilly antibodies are fairly far along in prophylaxis studies.

Q: Are there any entities ensuring representative samples, e.g. race?

A: A tremendous amount of time is being spent specifically focusing on making sure there are sites that can and will enroll people of color, as well as people with comorbidities. There is a full-scale effort with recruitment ads on TV and other outreach efforts to interest people with greater risk to enroll. There is ongoing training and community education to respond to skepticism amongst individuals about the trials and safety concerns.

HIV Updates

Recent HIV research highlights were presented:

  • Earlier in the summer, the long-acting cabotegravir in men study demonstrated superiority to oral PrEP.
  • On July 24, the dapivirine vaginal ring for HIV prevention received a positive opinion from the European Medicines Agency (EMA). Manufacturing and distribution strategies are currently being worked on.

NIAID HIV/AIDS Clinical Trials Network Recompetition Timeline

Network awards (Leadership and Operations Centers, Statistical and Data Management Centers, Laboratory Centers) and the Clinical Trials Units (CTU) awards are expected to be made on time, by December 1. These awards reflect clinical trials activities for HIV. Ongoing coronavirus activities that are embedded within the Networks and that are ongoing will not be impacted. These are parallel structures working within the same organizations.

Upcoming Meetings

  • January 25, 2021 (ARAC) - VIRTUAL
  • January 26 and 27, 2021 (AVRS) - VIRTUAL
  • June 7, 2021 (ARAC)
  • June 8 and 9, 2021 (SWG)
  • September 13, 2021 (ARAC)
  • January 31, 2022
  • June 6, 2022
  • September 12, 2022

Office of AIDS Research Advisory Council (OARAC) Update

Tricia Burdo, Ph.D.

Highlights of the 54th OARAC meeting held on June 25, 2020 were presented.

OAR Director’s Report:

Diversity and Inclusion at NIH

This topic covered Dr. Collins’ address to all NIH staff and an OAR internal listening session that referenced recent demonstrations in relation to the pervasive and systemic racism in the country.

HPTN 083

Large-scale clinical trial of long-acting injectable cabotegravir is highly effective for the prevention of HIV infection in cisgender men and transgender women who have sex with men.

NIH/OAR Updates

The FY Professional Judgment (PJ) Budget is being finalized.
The OAR website has a new look.

Upcoming Activities:

  • AIDS 2020 (23rd International AIDS Conference) – Virtual
    • NIH/OAR satellite session: The Impact of NIH HIV/AIDS Research and Discovery at the Intersection of Prevention, Treatment, and Disparities Across the Lifespan
  • Upcoming workshops include HIV-Related Intersectional Stigma Research Advances and Opportunities (co-organized with National Institute of Mental Health), and Early-Stage Investigators
  • OAR will initiate new listening sessions to re-engage with the community

Response to COVID-19:

  • NIH internal COVID-19 responses that include a maximum telework environment, convening townhall style meetings
  • Guidance for NIH-funded clinical research studies and NIH COVID-19 supplemental funding
  • Operation Warp Speed (OWS), Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), and the NIH Rapid Acceleration of Diagnostics (RADx) initiative
  • COVID-related HIV research activities at NIH

OAR Activities Related to COVID-19:

  • AIDSinfo: Interim Guidance for COVID-19 and Persons with HIV
  • OAR involvement in development and planning of NIH-wide initiatives
  • OAR developed policy for review of IC NOSIs for HIV and COVID represent NIH on PACHA
  • CAPT Mary Glenshaw deployment to COVID-19 testing site
  • OAR COVID-19 and HIV Taskforce

HIV Antiretroviral and OI Guidelines Working Groups of OARAC:

  • Opportunistic Infections in HIV-Infected Adults and Adolescents
  • Interim Guidance for COVID-19 and Persons With HIV

OARAC Ending the HIV Epidemic (EHE) Opportunities Analysis

Objectives:

  • Review research opportunities suggested during the February 2020 OARAC EHE Leadership Panel discussion; determine the responsiveness of the current NIH EHE research portfolio with research opportunities identified; and continue feedback with OARAC about NIH EHE research activities and opportunities.

OAR Task Force on COVID-19 and HIV

Critical areas to watch in the HIV and COVID-19 space:

  • Comparative health disparities: U.S. vs global; novel approaches and methods; intersectional research: COVID-19 and HIV; and ramifications of competition for resources

OARAC Discussion: Research Recovery Planning and Efforts

  • What challenges have institutions faced and how has the pandemic affected personnel?
  • What are institutions implementing to prepare for a potential second wave?
  • How many HIV researchers have pivoted to focus on COVID-19?
  • Other implications for personnel?

Questions: None

Concept Reviews (Approval Requested)

The following four FY 2022 DAIDS concepts were presented to the Committee for approval:

Therapeutics Research Program

Advancing Vaccine Adjuvant Research for Tuberculosis (TB)

Daniel Frank, Ph.D.

The objective of this new N01 initiative is to direct preclinical/translational research to identify, compare, and develop adjuvants in combinations with TB immunogens to improve TB vaccine effectiveness. The importance of this initiative was outlined and included that people living with HIV (PLWH) have a 10-times increased risk of TB disease activation and often suffer from poor outcomes to TB treatment; adjuvants in vaccine formulations induce potent immune responses that cannot be obtained with antigen alone; vaccine adjuvants being tested in TB clinical trials are currently limited; and a wider range of promising adjuvant options (innovative strategies from cancer and other fields) are now available to study specifically Mycobaterium tuberculosis-targeted responses. The goal of this initiative is to identify and advance optimal adjuvant-antigen combinations for use in people with TB/HIV. The scope of the initiative will involve using single and combination candidate adjuvants with TB antigens including targeted delivery formulations will be selected and systematic/standardized head-to-head comparison of promising antigen and adjuvant combinations with optimized profiling techniques. The current TB vaccines and adjuvants in the clinical pipeline or in trials were reviewed. The NIAID/DAIT adjuvant product pipeline and program was reviewed. This included TLR agonists/ligands targets (TLR 2, 4, 7, 8, and 9 receptors), broad disease focus covering HIV and cancer amongst many others and preclinical discovery work. The overall concept was presented diagrammatically then the reviewers’ comments and suggestions were summarized, and their responses were discussed.

Discussion:

Q: What is an N01 mechanism?

A: It is an activity code placeholder for a contract mechanism.

Ballot Voting Outcome:

10 Approval
0   Approval with modification(s)
0   Deferral for further information
0   Disapproval

Clinical Pharmacology Quality Assurance (CPQA) Program

Joe Fitzgibbon, Ph.D.

The objective of this renewal request for proposals (N01) contract initiative is to provide a resource to evaluate and enhance the quality and validity of pharmacology data generated in U.S. and non-U.S. clinical pharmacology laboratories participating in NIAID-funded and collaborative therapeutic and prevention clinical trials. The rationale for this initiative is that accurate pharmacology data are required to support NIAID/DAIDS scientific priorities, which include the development of new therapeutic strategies to achieve sustained virologic control and prevent transmission; evaluation of PK/PD during pregnancy and in infants and children to determine optimal regimens; and assessment of adherence and exposure to antiretrovirals for HIV prevention and treatment studies via objective metrics. In addition, CPQA provides a critical resource for NIAID-funded clinical pharmacology labs including the independent, external quality assessment of clinical pharmacology research conducted within NIAID’s research portfolio (network and non-network studies). A list of drugs used in studies in recent years was presented. The key activities that the contractor is expected to perform were discussed and include: monitoring the ability of labs to perform pharmacology testing through an ISO-certified Proficiency Testing program; supporting the development, validation, and implementation of pharmacology assays for drugs and matrices; acquiring, characterizing, storing, and distributing quality control materials and reagents; providing guidance, assistance and training to laboratory and clinical site staff; preparing pharmacology labs for FDA and other regulatory inspections and study audits; maintaining data management systems for tracking and managing clinical pharmacology quality assurance activities; and disseminating results. CPQA accomplishments and publications from the current contract (May 2015-present) were listed. The ARAC reviewers of this concept were supportive and their comments and suggestions were summarized, and their responses were discussed.

Questions: None

Ballot Voting Outcome:

10 Approval
0   Approval with modification(s)
0   Deferral for further information
0   Disapproval

Vaccine Research Program

Innate Immune Memory Impacting HIV Acquisition and/or Control

Que Dang, Ph.D.

The purpose of this new R21 initiative is to stimulate exploratory research examining innate immune cell effector functions that can be elicited to prevent HIV infection and replication. The rationale for this concept comes from the research gap in HIV vaccines where there is a lack of protective vaccine strategies that exploit both arms of the immune system so there is an unmet need to protect during the immunization phase. Therefore, potential vaccine strategies developed from this initiative will aim to engage innate immune cell effector functions to rapidly protect after immunization and potentially to synergize with adaptive immune responses. This is important because most HIV vaccine candidate platforms require immune maturation that takes up to one year to induce protective immunity and rely primarily on the adaptive immune response. Expanding the window of protection (during and after vaccination) by engaging all arms of the immune system will increase vaccine efficacy.

Recent research has suggested that innate immune cells such as natural killer cells (NK), dendritic cells (DCs), and monocytes/macrophages may be primed after encounter with antigen and acquire enhanced effector function against the same or unrelated pathogens (cross-protection). Functional reprogramming of the innate cells through metabolic and epigenetic changes is thought to maintain the cells in a “ready state.” Thus, upon a secondary exposure, the immune cells are ready to respond with an increased antimicrobial function such as phagocytosis, production of proinflammatory cytokines, or killing capacity.

This concept proposes that through HIV vaccination, innate memory can be potentially induced. By reprogramming innate immune cells to be in a ready state, then perhaps upon HIV exposure, enhanced innate immune effector functions can protect a person during the entire immunization phase until an efficacious, protective adaptive immune response can occur.

Examples of key research areas to be addressed: Does HIV induce innate immunity; what mechanisms regulate innate immunity which could impact HIV acquisition; can innate memory functions be augmented for more effective HIV vaccine strategies? Accordingly, there is a broad scope of research encompassing basic molecular mechanisms to translational research.

The ARAC reviewers were supportive of this new concept.

Questions: None

Ballot Voting Outcome:

10 Approval
0   Approval with modification(s)
0   Deferral for further information
0   Disapproval

Vaccine Research Program/Basic Sciences Program

Consortia for Innovative AIDS Vaccine and Cure Research (CIAR)

Nancy Miller, Ph.D., and Brigitte Sanders, D.V.M., Ph.D.

The purpose of this UM1 renewal initiative is to conduct innovative vaccine and therapeutic studies in nonhuman primate (NHP) models for AIDS. This will comprise two main areas:

Focus 1: Vaccines – Characterize vaccine-induced responses shown to protect NHPs from mucosal infection by SIV/SHIV: Identify correlates and understand mechanisms of protection; Focus 2: Cure – Develop immunological interventions, including vaccines, with the goal of eliminating viral reservoirs (cure) or enhancing virus control (generate elite controllers). This initiative will continue studies that use NHP models because they can replicate most of the important features of HIV immunogenicity and pathogenesis in humans, such as the generation of immune responses to viral proteins, susceptibility to mucosal route infection, persistent plasma viremia and establishment of persistent tissue proviral reservoirs. NHP models offer advantages to both vaccine and cure research, allowing tissue sampling (including necropsy), virus challenge, prolonged analytic treatment interruption in cure studies and testing of innovative, highly experimental interventions.

The rationale for combining vaccine and cure research in this concept is based on several considerations, including:

  • Collaborations between vaccine and cure researchers can stimulate innovative approaches to cure.
  • Immunological approaches, including vaccines, adjuvants, or monoclonal antibodies can be applied to cure research as potential ways to improve immunological control of virus replication, reduce post-ART viral rebound, or reduce viral reservoirs.

Focus 1 (Nancy Miller)

The goals of this Focus are:

  • To identify the correlates of protection afforded by vaccines that reduce the rate of acquisition or prevent establishment of infection after mucosal challenge in NHPs.
  • To understand the underlying mechanisms of vaccine protection in NHPs and provide a basis for rational vaccine design to improve efficacy and enable translation to other vaccines, including human HIV vaccines.

The CIAR accomplishments for vaccine research were briefly reviewed and covered work on protection seen in NHP studies with rhesus CMV-vectored SIV vaccines, Ad-26/Env SIV vaccines, the HIV Env SOSIP protein trimer in 3M052 adjuvant, administered in combination with recombinant vectors, and the HIV DNA/MVA/SOSIP-BG505 prime-boost regimen.

Expectations for potential applicants, as well as examples of areas for investigation, were presented.

Focus 2 (Brigitte Sanders)

The background of this focus is as follows:

  • HAART only limits viral replication and is not viricidal; thus, cells infected with HIV provirus will persist under HAART.
  • Many clinical HIV cure studies have been performed with few successes; it has been proven difficult to eliminate a large portion of the integrated HIV replication-competent provirus.
  • While recent preclinical studies using immunological approaches to control or prevent viral rebound have been promising, new or improved immunological approaches are needed to maintain a long-term, virus-free state.

Current CIAR cure research accomplishments were listed as publications and included three studies that employed PGT121 antibody combined with TLR-7, the N-803 IL-15 superagonist in combination with CD8 depletion, and the novel latency reversal agent AZD5582.

Suggestions on what applicants are expected to propose for the cure Focus of this FY 2022 initiative were presented.

Applicants to this initiative must submit an application that proposes a multidisciplinary program that addresses both vaccine and cure research areas. They will be expected to define the overall structure of the Consortium, including approaches to integrate findings from vaccine responses and approaches to cure studies.

The ARAC reviewers fully supported continuing this initiative. Their comments and suggestions were summarized and responses to them were discussed.

Question:

Q: How does this fit in with the DAIDS Martin Delaney Cure Collaboratories?

A: We are trying to distinguish ourselves from the Collaboratories but also work closely with them. The approach is supposed to be complimentary and is able to assist with their limited resources if needed.

Ballot Voting Outcome:

10 Approval
0   Approval with modification(s)
0   Deferral for further information
0   Disapproval

VII. Adjournment

The meeting of the Council adjourned at 3:45 p.m., on Monday, September 14, 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

01/15/2021

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

01/14/2021

Date

 

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

Content last reviewed on