NIAID Council Minutes: June 5, 2017

The 186^th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened at 10:00 a.m. on Monday, June 5, 2017, in Conference Rooms E1/E2, Building 45, National Institutes of Health. Dr. Anthony S. Fauci, director, National Institute of Allergy and Infectious Diseases (NIAID) presided as chair.

In accordance with the provisions of Public Law 92-463, the meeting was open to the public from 10:00 a.m. to 11:45 a.m. and from 1:00 p.m. to 4:25 p.m. The meeting was closed to the public from 8:30 a.m. to 9:45 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.

Table of Contents

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

I. Review of Grant Applications

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

Funding Actions: The Council reviewed 4,911 research and training applications with primary assignment to NIAID for a requested amount of $1,391,687,445 in first-year direct costs and recommended approval of 2,258 applications with $747,666,582 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 three nominated Council members whose appointments are still pending and were attending as ad hoc Council members: Dr. Mark Feinberg, president and CEO of the International AIDS Vaccine Initiative; Dr. Stanley Lemon, professor of medicine and microbiology and immunology at the University of North Carolina; and Dr. Robin Patel, chair of the Division of Clinical Microbiology at the Mayo Clinic. He also introduced two other ad hoc members: Dr. Ofer Levy, director of the Precision Vaccines Program at Boston Children’s Hospital and associate professor of pediatrics at Harvard Medical School, and Dr. Joan Cook-Mills, professor of medicine in the Division of Allergy and Immunology at Northwestern University.

Consideration of Minutes of Previous Meeting

Council considered the minutes of the January 30, 2017 meeting and approved them as written.

Appointments and Transitions

On May 9, the U.S. Senate confirmed Dr. Scott Gottlieb as FDA commissioner. Dr. Gottlieb is a physician and resident fellow at the American Enterprise Institute.

On May 23, Member States of the World Health Organization elected Dr. Tedros Adhanom Ghebreyesus as its new director general. He recently served as Ethiopia’s Minister of Foreign Affairs.

Staff and Organizational Changes

Dr. Cathy Laughlin retired as chief of the Virology Branch in the Division of Microbiology and Infectious Diseases. Dr. Cristina Cassetti is currently serving as acting branch chief.

Tributes and Awards

At the annual meeting of the American College of Physicians on March 30, Dr. Cliff Lane was named a Master of the American College of Physicians.

Dr. Yasmine Belkaid, chief of the Mucosal Immunology Section in the Laboratory of Parasitic Diseases, recently received two honors. In March, Dr. Belkaid was awarded the Emil von Behring Prize for her research on the interrelationship of the human immune system and the microbiome. In May, she was elected to membership in the National Academy of Sciences.

Dr. Josh Milner, chief of the Genetics and Pathogenesis of Allergy Section in the Laboratory of Allergic Diseases, received the second annual Gale and Ira Drukier Prize in Children’s Health Research at Weill Cornell Medicine. The award honors early-career pediatricians whose research has made important contributions towards improving the health of children and adolescents.

Dr. June Kwon-Chung, chief of the Molecular Microbiology Section in the Laboratory of Clinical Infectious Diseases, was honored with the American Society of Microbiology Lifetime Achievement Award, which is awarded for sustained contributions to microbiological sciences.

In March, Dr. Dean Metcalfe, chief of the Laboratory of Allergic Diseases and associate director of the Allergy and Immunology Training Program, was named the 2017 recipient of the American Academy of Allergy, Asthma, and Immunology Mentorship Award.

In April, Dr. John Bennett, chief of the Clinical Mycology Section in the Laboratory of Infectious Diseases, received the American College of Physicians Jane F. Desforges Distinguished Teacher Award.

Dr. Frank DeLeo, chief of the Laboratory of Bacteriology, has been elected to the American Academy of Microbiology.

Dr. Peter Crompton, chief of the Malaria Infection Biology and Immunity Unit in the Laboratory of Immunogenetics, has been inducted into the American Society of Clinical Investigation.

Meetings and Events

On February 21, HHS Secretary Dr. Tom Price visited NIH. During his visit, he toured the Clinical Center and met with NIH senior leadership.

Several high-level international delegations came to NIAID to meet with Dr. Fauci to discuss scientific topics of mutual interest, including Middle East Respiratory Syndrome coronavirus, influenza, yellow fever, and antimicrobial resistance. The visiting delegations represented Angola, Germany, Rwanda, Saudi Arabia, Canada, Hong Kong, and Sweden.

On April 8, Dr. Fauci participated in a plenary panel during the 8^th Annual Conference of the Consortium of Universities for Global Health, held in Washington, D.C.

On April 12, the Indo-U.S. Vaccine Action Program celebrated its 30^th anniversary. Dr. Fauci participated in the celebration and delivered the Raba-Robbins keynote lecture on emerging infectious diseases.

On April 21, Dr. Fauci participated in a meeting of the Decade of Vaccines Leadership Council. The meeting included an open discussion about progress towards the goals and objectives laid out in the Global Vaccine Action Plan.

On May 9, Dr. Larry Corey delivered the 2017 James C. Hill Memorial Lecture, “Getting to an Effective HIV Vaccine: Perspectives on Progress.”

On June 2, Dr. Francis Collins, Dr. Fauci, and other scientific leaders at NIH participated in a meeting with the Bill and Melinda Gates Foundation, which focused on global health issues, research capacity building in Africa, and HIV prevention science. In the afternoon, Dr. John Mascola, director of the Vaccine Research Center (VRC), his team, and Dr. Fauci toured the VRC with Mr. Gates.

Budget Update

NIH began fiscal year 2017 operating under a continuing resolution (CR). Two additional CRs were passed extending funding to May 5, when President Trump signed the omnibus spending bill for FY 2017.

For FY 2017, NIH received an increase of 6 percent, with most institutes receiving between a 3 and 5 percent increase. NIAID received a 3.3 percent increase over FY 2016, which included $50 million for antibiotic resistance research to continue the President’s National Strategy for Combating Antibiotic-Resistant Bacteria.

Dr. Fauci summarized NIAID’s financial management plan for FY 2017. The Institute’s R01 payline is the 11 percentile for established investigators and the 15 percentile for new investigators. NIAID will not make programmatic adjustments to competing, unsolicited awards; noncompeting grants; or research and development awards. Program initiatives may be cut by up to 10 percent in order to sustain investigator-initiated awards. NIAID’s estimated success rate will be between 20 and 22 percent.

On May 23, Mick Mulvaney, director of the Office of Management and Budget, presented the President’s Budget for Fiscal Year 2018 to Congress, which includes a decrease of 21 percent from NIH’s FY 2017 enacted budget level. Most institutes receive reductions exceeding 20 percent. Dr. Fauci noted that Congress ultimately determines the budget.

Legislative Update

On February 6, Representative Tom Cole, chair of the House Appropriations Subcommittee on Labor-HHS, visited NIH along with several Subcommittee members and staff. Dr. Fauci, Dr. Collins, and select institute and center directors discussed NIAID research and priorities with this congressional delegation.

On March 7, Dr. Fauci spoke at a congressional briefing on antimicrobial resistance sponsored by the Infectious Diseases Society of America. He was joined by representatives from CDC, Biomedical Advanced Research and Development Authority (BARDA), and Department of Defense.

On April 12, the majority and minority clerks for the Senate Appropriations Subcommittee on Labor-HHS visited NIH. Dr. Fauci briefed them on high-priority areas of research, including Zika, Ebola, HIV/AIDS, influenza, malaria, and antimicrobial resistance.

On May 17, Dr. Collins testified before the House Appropriations Subcommittee on Labor-HHS about NIH biomedical research. Dr. Fauci accompanied him and provided updates on NIAID efforts on Zika, Ebola, HIV/AIDS, H7N9 influenza, and tuberculosis. Other institute directors also attended.

On May 23, Dr. Fauci testified at a hearing of the House Energy and Commerce Subcommittee on Oversight and Investigations to review the U.S. public health response to the Zika virus outbreak. He was joined by representatives from BARDA, CDC, FDA, and the Government Accountability Office.

Dr. Fauci recognized NIAID staff members who participated in congressional activities since the last Council meeting.

Other Information Items

Dr. Fauci began with an update on Zika, summarizing a molecular epidemiological study, which showed that there were multiple introductions of Zika virus into the U.S.

He presented statistics of suspected and confirmed Zika cases in South America, the Caribbean, and Central America. He also reported cases of Zika virus disease and Zika-affected pregnancies and outcomes in the U.S. and U.S. territories.

Dr. Fauci noted that doctors have found that some adults who are infected with Zika have developed cardiovascular complications. He concluded with an update on NIAID’s Zika vaccine efforts.

Dr. Fauci gave brief updates on Ebola, influenza, yellow fever, and respiratory syncytial virus (RSV), and mentioned the NIAID Strategic Plan 2017, that was recently updated.

III. Guest Speakers

John R. Mascola, M.D., director, Vaccine Research Center

Dr. John Mascola began by noting that the VRC was founded to do HIV vaccine research. However, the vaccine technologies that VRC employs are now directed to a number of diseases, including Ebola, influenza, and RSV.

Dr. Mascola outlined VRC’s organizational structure that is used to do basic science research through to clinical trials. He also gave an overview of VRC’s product development portfolio.

He highlighted two of VRC’s major programs, the HIV antibody prevention program and Zika vaccine development program.

Dr. Mascola presented details on the Antibody Mediated Prevention Study, which is a Phase 2b efficacy study that is now enrolling patients through the Division of AIDS-sponsored large clinical trials networks, the Vaccine Trials Network and Prevention Trials Network. VRC is producing the antibody for this Phase 2b study.

He concluded by giving an update on VRC’s Zika vaccine development efforts, focusing on the Zika DNA vaccine, and mentioning other approaches to Zika virus vaccine development that are being conducted.

Lawrence A. Tabak, D.D.S., Ph.D., principal deputy director, NIH

Dr. Lawrence Tabak began by referencing the NIH-Wide Strategic Plan, Fiscal Years 2016-2020: Turning Discovery Into Health, which includes the objective of enhancing scientific stewardship. To work towards achieving this objective, NIH must recruit and retain an outstanding biomedical research workforce and enhance workforce diversity. He then mentioned the 21^st Century Cures Act, which directs the NIH director to promote policies that ensure earlier independence and increased funding for new investigators.

Next, Dr. Tabak presented NIH’s plan to implement the Grant Support Index, a new policy to help support more early-stage and mid-career investigators by limiting the number of grants that any single investigator can have at one time. He thanked everyone for their comments and feedback and fielded questions.

Note: Following the NAAIDC meeting on June 5, 2017, NIH decided to adopt a different strategy to support early-stage and mid-career investigators, the Next Generation Researchers Initiative.

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

Dr. Rotrosen welcomed the subcommittee members to the 186^th meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting:

Dr. Rotrosen presented the following new staff members, Division activities, and concept reviews:

Staff and Organizational Changes

Paul W. Price, Ph.D. Dr. Price joined the Office of Regulatory Affairs in January 2017 as a regulatory affairs officer. He received his Ph.D. in biology (immunology) from Georgetown University and completed post-doctoral training at the Department of Microbiology and Immunology, University of Maryland School of Medicine. Dr. Price has over 25 years of experience in drug discovery and development across multiple therapeutic areas, diagnostics, and medical devices; as well as regulatory experience. Most recently, he served as principal scientist at Paragon, senior consultant at Biologics Consulting, and principal consultant at PWPrice Consulting.

Chao Jiang, Ph.D. Dr. Jiang joined the Basic Immunology Branch in January 2017 as a program officer. She received her Ph.D. in microbiology and immunology from the University of Virginia and came to NIH as an IRTA fellow in 2010. Her laboratory research was focused on molecular mechanisms of B cell function in the context of autoimmunity. Dr. Jiang subsequently worked as a program analyst at the National Center for Complementary and Integrative Health (formerly the National Center for Complementary and Alternative Medicine) before being recruited to the extramural program of National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Division Activities

Allergy, Asthma, and Airway Biology Branch

Peanut Allergy Guidelines Implementation and Validation Workshop. On February 6, 2017, NIAID organized a workshop in Rockville, Maryland, to discuss strategies for assessing the impact of the recently developed Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel. Invited participants proposed and discussed a program to monitor the success of the implementation of the guidelines and their impact on the prevalence of peanut allergy in the United States. The proposed program will be based on surveys of pediatricians, allergists, and parents.

Stevens-Johnson Syndrome/Toxic Epidural Necrolysis 2017: Building Multidisciplinary Networks to Drive Science and Translation. On March 2, 2017, NIAID, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Human Genome Research Institute co-sponsored a meeting in Orlando, Florida, to encourage new investigators, trainees, women, and minorities across multiple scientific and clinical disciplines, patients and patient advocacy groups to become involved in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) research. The program included presentations and discussions from more than 20 domestic and international experts on SJS/TEN and related disciplines. The goals of the meeting were to: 1) create networks, 2) prioritize research goals and unanswered questions, 3) provide mentorship for new investigators and trainees, 4) assemble key researchers for presentation of cutting edge research, and 5) address potential barriers to short and long-term progress in SJS/TEN research.

New Concepts on the Pathogenesis and Treatment of Atopic Dermatitis: NIAID Morning Course at the AAAAI Meeting. On March 3, 2017, NIAID organized a course entitled “New Concepts on the Pathogenesis and Treatment of Atopic Dermatitis” as part of the annual meeting of the American Academy of Allergy, Asthma, and Immunology (AAAAI), in Atlanta, Georgia. Experts in the field presented lectures on the skin barrier and its role in atopic dermatitis (AD), the pathogenesis of inflammation and infection in AD, genetics of AD, the relationship between AD and food allergy, and treatment and prevention of AD.

Aspirin-Exacerbated Respiratory Disease I: Advances in Basic Biology and Pathophysiologic Mechanisms. On March 3, 2017, the Asthma and Allergic Diseases Cooperative Research Centers (AADCRC) organized a course entitled “Aspirin-Exacerbated Respiratory Disease I: Advances in Basic Biology and Pathophysiologic Mechanisms” as part of the annual meeting of the AAAAI in Atlanta, Georgia. Experts in the field presented lectures on epigenetics of aspirin-exacerbated respiratory disease (AERD) and the effects of high-dose aspirin, the amplification of Th2 immunopathology by cysteinyl leukotrienes in AERD, the control of human airway function by prostaglandins, the spectrum of nasal polyp lymphocyte populations, and thymic stromal lymphopoietin as a master regulator of nasal polyposis and AERD.

Microbiome: The Essentials, Immunologic and Genetic Effects, and Influence on Atopy and Asthma. On March 3, 2017, the Inner-City Asthma Consortium (ICAC) organized a course entitled “Microbiome: The Essentials, Immunologic and Genetic Effects, and Influence on Atopy and Asthma” as part of the annual meeting of the AAAAI, in Atlanta, Georgia. Experts in the field presented lectures on the exogenous and endogenous microbiomes; airway and gut microbiota and their immunologic effects; the effects of pets and pests on the microbiome and implications in atopy development; asthma exacerbations related to airway microbiome and virus/bacteria interactions; and the alteration of airway gene expressions by respiratory infections.

Lipid Mediators in Asthma: New and Old, Good and Bad. On March 3, 2017, the AADCRC organized a course entitled “Lipid Mediators in Asthma: New and Old, Good and Bad” as part of the annual meeting of the AAAAI, in Atlanta, Georgia. Experts in the field presented lectures on prostacyclin inhibition of ILC2 function, group 6 phospholipase A2-derived linoleic acid regulation of type 2 immunity, and prostaglandin E2 control of allergic inflammation.

The Contribution of Structural Cells to Asthma Pathogenesis: Lessons from the AADCRC. On March 4, 2017, the AADCRC organized a workshop entitled “The Contribution of Structural Cells to Asthma Pathogenesis: Lessons from the AADCRC” as part of the annual meeting of the AAAAI, in Atlanta, Georgia. Experts in the field presented lectures on modulation of force generation by airway smooth muscle, ORMDL2 and airway remodeling in asthma, and the sensitivity of airway structural cells to type 2 inflammation defining allergic asthma.

Prostaglandin Regulation of Allergic Diseases. On March 5, 2017, the AADCRC organized a seminar entitled “Prostaglandin Regulation of Allergic Diseases” as part of the annual meeting of the AAAAI, in Atlanta, Georgia. Two investigator’s presented lectures on the mechanisms by which prostaglandins are synthesized in the setting of allergic inflammation, the roles of individual prostaglandins in propagating or restraining allergic inflammatory responses, and the role of prostaglandin regulation as therapy for allergic diseases.

Pathways to the Development of Asthma: Lessons from the Inner-City Asthma Consortium. On March 5, 2017, the Inner-City Asthma Consortium (ICAC) organized a symposium entitled “Pathways to the Development of Asthma: Lessons from the Inner-City Asthma Consortium” as part of the annual meeting of the AAAAI, in Atlanta, Georgia. Three investigators presented lectures on environmental allergy and microbial influence on the development of asthma, environmental determinants and causative pathways leading to asthma severity, and genetic pathways that may regulate the development of asthma.

Basic Immunology Branch

Immune Surveillance by Non-Classical Major Histocompatibility Complex (MHC) Molecules. On March 16, 2017, DAIT, the Division of AIDS, the Division of Microbiology and Infectious Diseases, and the Bill and Melinda Gates Foundation co-sponsored a workshop to highlight the role of non-classical MHC restricted T cells in infection and discuss how these cells could be elicited to broaden the repertoire of anti-pathogen responses to help prevent or treat HIV and other infections. Workshop participants were asked to focus on current examples from diseases, assays, and technology to measure responses; antigen processing; and T cell recognition, perspectives, and future directions.

Human Immunology Project Consortium II (HIPC II) Annual Meeting: On March 22 and 23, 2017, DAIT sponsored the first annual meeting of this research program in Rockville, Maryland. This meeting included updates from the three HIPC sites awarded in 2015 (Emory University, Icahn School of Medicine at Mount Sinai, and La Jolla Institute of Allergy and Immunology at the University of California, Berkeley) and introductory presentations from three new sites awarded in late-2016 (Boston Children’s Hospital, Columbia University, and Yale University). The HIPC program supports research to define, analyze, and correlate molecular profiles of varied human immune responses to infection or vaccination, with the goal of helping to define the human immune system and its responses to antigen exposure. Data generated by the HIPC investigators are being made available to the broader research community through ImmPort and ImmuneSpace, which is a powerful data management and analysis engine for the exploration and analysis of HIPC-generated datasets using state-of-the-art computational tools.

Immune Mechanisms of Virus Control (IMVC) Program Annual Meeting. On April 19 and 20^, 2017, NIAID convened the annual meeting for the IMVC program in Rockville, Maryland. This program consists of eight research projects focused on varying immunological questions on the host response to viral infection or vaccination. The meeting included presentations by investigators on their progress within the previous year and provided opportunities to establish new collaborations.

Symposium on Aging and Immunity. From May 10 to 12, 2017, NIAID and the National Institute on Aging co-sponsored a symposium to discuss recent progress in understanding the immunology of aging. The symposium promoted critical discussions in three areas: 1) improving immune responses in the elderly to infectious diseases, cancers, and vaccines; 2) fostering interactions and collaborations among scientists; and 3) encouraging new and junior investigators to enter this research area. Featured were eight scientific sessions evaluating current information on aging of stem cells; precursor immune cells and tissue; epigenetic regulation of aging immune cells; metabolism and aging; infectious diseases, vaccines, cancers, and inflammatory and autoimmune disorders in the elderly; and longitudinal studies on aging. Discussion explored potential avenues of further research in these areas, identifying both research gaps and strategies to strengthen immune function in older individuals.

NIAID Mouse Model Symposium at the 2017 Annual Meeting of the American Association of Immunologists. On May 13, 2017, NIAID held a symposium at the Annual Meeting of the Association of Immunologists held in Washington, D.C. The goal of the symposium was to discuss how diverse mouse models could be used for the advancement of immunological research and our understanding of human immunology. The symposium featured four areas of interest: 1) the use of non-specific-pathogen-free mice (i.e., dirty mice); 2) CRISPR-Cas9 technology uses to generate novel mouse models; 3) methods to use the Collaborative Cross mouse resource to identify complex genetic interactions regulating immunology; and 4) the use of N-Ethyl-N-Nitrosourea induced mutagenesis to generate mice for high-throughput screening.

B Cell Epitope and Mechanisms of Antibody Protection, Large Scale T Cell Epitope Discovery, and Immune Epitope Database and Analysis Resource (IEDB) Annual Progress Meeting. On May 17 and 18, 2017, the annual meeting of the B Cell and T Cell Epitope Discovery Programs and IEDB was held in Rockville, Maryland. During the meeting, investigators provided updates from the B Cell Epitope Discovery contract. T Cell Epitope Discovery contract investigators also presented their progress. The IEDB contract, which maintains a large database of the epitope data from the B and T cell discovery contracts as well as from the literature, presented goals of the program and progress from epitope data deposited. At the end of the second day of this meeting, a working group meeting was held with NIAID staff and external working group members to provide feedback to NIAID on the progress and success of the program overall.

Modeling Immunity for Biodefense Annual Program Meeting. On June 1, 2017, the annual programmatic meeting of the Modeling Immunity for Biodefense (MIB) initiative was held in Rockville, Maryland. The goals of the annual meeting were to update NIAID staff and investigators on research progress and facilitate communication and collaboration among the four supported awardees. During the meeting, investigators presented their recent results and research plans for the coming year. The overall goal of the MIB program is to build computational models of immunology to better understand and study the immune response to infection or vaccination. The scientific meeting was followed by a brief steering committee meeting to discuss integration between centers, recommendations from the external scientific advisory group, current Infrastructure and Opportunities Fund projects and future output, and the planning and execution of future symposia and summer schools for training the broader immunology community in computational modeling.

Autoimmunity and Mucosal Immunology Branch

None

Radiation and Nuclear Countermeasures Program (RNCP)

Chrysalis Biotherapeutics, Inc. kick-off meeting for contract HHSN272201700011C: On March 9, 2017, the RNCP held a kick-off meeting in Rockville, Maryland to initiate the funding of a new contract with Chrysalis Biotherapeutics, Inc. in response to the Program Broad Agency Agreement “Development of Radiation/Nuclear Medical Countermeasures or Biodosimetry Devices.” The concept for the award is to develop TP-508 thrombin peptide as a product targeting radiation-induced endothelial cell damage by restoring capillary networks and maintaining the stem cell niche to promote tissue regeneration and increasing survival in an established animal model.

Chromologic kick-off meeting for contract HHSN272201700012C: On March 28, 2017, the RNCP held a kick-off meeting in Rockville, Maryland, to initiate the funding of a new contract with Chromologic LLC in response to the Program Broad Agency Agreement “Development of Radiation/Nuclear Medical Countermeasures or Biodosimetry Devices.” The concept for the award is to develop a biological signature that will permit the distinction between the irradiated and the non-irradiated population in the event of a large scale nuclear disaster. Further, this contract intends to predict the appearance of delayed radiation injury and potential outcome for intervention strategy.

University of Florida kick-off meeting for contract HHSN27220170008C: On April 3, 2017, the RNCP held a kick-off meeting in Rockville, Maryland to initiate the funding of a new contract with the University of Florida in response to the Program Broad Agency Agreement “Development of Radiation/Nuclear Medical Countermeasures or Biodosimetry Devices. The concept for the award is to develop FGF-P as a product that reduces acute radiation-induced gastrointestinal syndrome through cooperating mechanisms that include decreasing cell loss, improving proliferation of small bowel mucosa, improving gut barrier function with reduced bacterial translocation, and supporting the integrity of the bone marrow with induction of granulocyte-colony stimulating factor.

Concepts Presented for Clearance

Autoimmunity Center of Excellence: The Autoimmunity Centers of Excellence (ACE) program is a cooperative network of integrated basic, preclinical and clinical research centers. It is being renewed in FY 2019.

The subcommittee endorsed and unanimously approved this grant topic.

NIAID Division of Allergy, Immunology, and Transplantation: Immune-Mediated Diseases Clinical Products Center (CPC): This initiative will facilitate the ability of the Division to fulfill its responsibility as a clinical trials sponsor to ensure that study products are received, stored, distributed, and accounted for in accordance with all federal rules and regulations and in a manner that maintains the quality of the products.

The subcommittee endorsed and unanimously approved this contract topic.

Investigations on Primary Immunodeficiency Disease: This initiative will support research project grant (R01) applications that propose innovative investigations in primary immunodeficiency diseases.

The subcommittee endorsed and unanimously approved this grant topic.

SBIR Radiation and Nuclear Countermeasures Program: The goal of this program is to provide funds for preclinical product development of drugs and devices that could lead to eventual FDA licensure and inclusion of products in the Strategic National Stockpile, for potential use during a nuclear or radiological incident.

The subcommittee endorsed and unanimously approved this contract topic.

Immunity in the Elderly: The objective of this program is to expand understanding of the changes that occur in immune function during the aging process that contribute to impaired responses to pathogens and vaccines.

The subcommittee endorsed and unanimously approved this grant topic.

Immune Epitope Database: The Immune Epitope Database and Analysis Resource is a public repository of immune epitope data and an Analysis Resource that makes a variety of analytical and epitope prediction tools available to the public. The objective is to enable the scientific community to have a better understanding of the nature of immune epitopes to expedite the development of new therapies to prevent and treat infection, organ and tissue rejection, and autoimmune and allergic disorders.

The subcommittee endorsed and unanimously approved this contract topic.

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 June 5, 2017. Dr. Erbelding welcomed three ad hoc members–Dr. Mark Feinberg, president and chief executive officer of the International AIDS Vaccine Initiative in New York; Dr. Stanley Lemon, professor of medicine, School of Medicine at UNC Chapel Hill; and Dr. Robin Patel, director of the Infectious Disease Research Laboratory at the Mayo Foundation for Medical Education and Research–and noted the intent to finalize their status as special government employees, and full Subcommittee members, as soon as the federal hiring freeze is lifted. She also noted the ex officio vacancy on the Subcommittee created by the recent departure of Dr. Bruce Gellin, former director of the National Vaccine Program Office in the Department of Health and Human Services. Dr. Erbelding reported one staff change, the recent appointment of Dr. Cristina Cassetti as the acting branch chief of DMID’s Virology Branch.

Dr. Erbelding provided several DMID research updates:

• She reported on the recent recompetition of the International Centers of Excellence for Malaria Research program, an NIAID flagship program to advance malaria research.
• She provided a brief overview of the Coalition for Epidemic Preparedness Innovations (CEPI), a recently launched partnership of public, private, philanthropic, and civil society organizations that aims to stimulate financing for and coordination of vaccine development efforts against priority threats. Initially, CEPI reported it would target three viruses: MERS, Lassa, and Nipah. CEPI will focus on moving vaccine candidates through late-stage preclinical development to proof-of-concept and safety in humans so that they are ready should an epidemic emerge. They also intend to build technical platforms and institutional capabilities that can be rapidly deployed against new and unknown pathogens. NIAID’s involvement in this effort will be earlier in the discovery phase through the support of basic research and early product development activities.
• She described two components of the 21st Century Cures Act, signed into law last fall, that will involve DMID staff: the establishment of a tick-borne disease working group and the development of a multiagency report on vaccine innovation.
• She provided an overview of the Combating Antimicrobial Resistant Bacteria Biopharmaceutical Accelerator program, CARB-X, a public/private partnership funded by the U.S. government through BARDA, and the Welcome Trust of the UK, with some additional in-kind support pledged by NIAID through the provision of preclinical resources. Ten awards were made in March, and Dr. Erbelding noted that DMID had previously provided discovery or development funding support for seven of these companies.

Program, Scientific, and Budget Updates

Vector Biology Programs at DMID: Moving from Basic Research to Translational and Field Studies - Dr. Malla Rao, program officer in DMID’s Parasitology and International Programs Branch, provided an overview of the Vector Biology Program (Dr. Rao presented on behalf of the Branch Chief, Dr. Lee Hall, who was unable to attend the meeting). Dr. Rao reported that DMID’s long-standing Vector Biology Program supports a wide array of research, spanning basic, translational, and clinical studies. In addition, NIAID maintains a variety of resources and related training opportunities for investigators. In particular, NIAID’s broad, sustained investment in vector biology has seeded new generations of vector control interventions that could impede malaria transmission, e.g., biopesticides that target mosquitoes only, and natural parasitic fungi or bacterial symbionts to kill mosquitoes or affect pathogen survival or transmission. It will be important to evaluate these promising interventions alongside existing interventions to determine the optimal combination of approaches to combat disease transmission. To this end, NIAID plans to support competitive supplements to the recently renewed International Centers of Excellence for Malaria Research network to pursue such studies.

Concepts Presented for Clearance

The following fiscal year 2019 concepts were presented to the Subcommittee:

Partnerships for Countermeasures Against Select Pathogens – This concept will support milestone-driven projects focused on advancement of candidate therapeutics, vaccines, and related countermeasures against select pathogens. The Subcommittee expressed support for the ongoing DMID Partnerships Program, noting that it provides an important mechanism to support academic and industrial communities in translational and preclinical product-related research and development efforts.

One Subcommittee member requested insight on the overall success of the program. The program is periodically evaluated (internally and externally) using multiple metrics, including numbers of marketed products, candidate products in late-stage development, candidate products in preclinical development, adaptation of new technologies/platforms, subsequent funding for continued development of a candidate, industrial participation, awardee feedback and publications. These evaluations have concluded that the Partnerships program plays a critical role in expanding the product development pipeline for development of countermeasures against targeted emerging and re-emerging pathogens. The Subcommittee member also inquired how the program has benefitted from mandated participation by industrial partners on academic awards. Program staff replied that required industrial participation facilitates NIAID objectives and ensures that awarded projects focus on advancing translational research and product development activities in adherence to agreed-upon milestones. No additional questions or comments were offered. The concept was unanimously approved.

Repurposing Target-Based Pharmaceutical Libraries for Discovery of Therapeutics Against Eukaryotic Pathogens – This concept will repurpose target-based pharmaceutical libraries for discovery of therapeutics against eukaryotic pathogens. The Subcommittee recognized that the combination of recent research advances in validated, target-based and whole cell high throughput screening platforms for eukaryotic pathogens, coupled with the availability of well-characterized pharmaceutical libraries, represents a scientific opportunity to accelerate drug development. Two Subcommittee members noted that the funding opportunity announcement must clearly state what constitutes a well-characterized pharmaceutical library. The concept was unanimously approved.

Centers of Excellence for Translational Research – This concept would renew support for multidisciplinary translational research centers focused on generating, validating, and advancing medical countermeasures to select emerging and re-emerging infectious diseases. The Subcommittee was impressed with the research accomplishments to date and voiced support for renewal of the Centers of Excellence for Translational Research (CETR) program. One Subcommittee member requested information about the role of milestones in directing the activities of each Center. Program staff clarified that milestones are proposed in the original application, are peer reviewed, and serve the important purpose of keeping investigators focused on the ultimate goal of conducting translational research. As the research progresses, milestones can be modified as new research opportunities arise. Program staff provided examples of how two CETRs adapted their research during the recent Ebola outbreak, to conduct rapid preclinical evaluation of candidate therapeutics. One Subcommittee member requested information about the process being used to evaluate the progress of each CETR, given that it appeared some were more productive than others. Program staff agreed that while there is variable performance, the current awardees are still in the early stage of the program and the research is showing which approaches are working and which are not, as is to be expected when novel approaches are being pursued. Another Subcommittee member asked for clarification regarding how Program attempts to ensure actual products will be generated by this program. Program staff emphasized that by providing funding for this stage of translational research, the CETRs are lowering the risk for industry partners to become involved, and that investigators with promising candidate products are encouraged to transition to other partners to obtain funding for continued development. The concept was unanimously approved.

Maintenance, Housing, and Research Support of Non-Human Primate (NHP) Colonies and Cohorts for the Vaccine Research Center (VRC) – This concept will facilitate the conduct of basic and translational research through NHP research protocols and is critical for the rapid preclinical testing of novel vaccine candidates. Support services may include the acquisition of NHPs, qualified personnel, materials, equipment, and facilities not otherwise provided by the government, necessary to perform the work. The required work may include purchasing, acquiring, transporting, establishing, and maintaining NHP research cohorts. The Subcommittee unanimously approved the concept, noting that it was central to the mission of the VRC.

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

Dr. Dieffenbach provided a budget update, covered the grant support index (GSI), and discussed the upcoming HIV Clinical Trials Network funding renewal.

Budget Update

The current administration signed an omnibus spending bill for FY 2017 on May 5, 2017 after starting the fiscal year under a continuing resolution that was extended multiple times. This budget led to an increased NIH level of funding of 5.9 percent with NIAID receiving an increase of 3.3 percent, most of which was the non-AIDS component. On May 23, 2017, the President’s budget request for FY 2018 was released. This outlined several proposed cuts to discretionary programs and the reorganization of NIH’s institutes and centers. Congress will make final determination on the budget, but Dr. Dieffenbach expects to start the fiscal year under a continuing resolution and a level budget.

Grant Support Index (GSI)

The GSI approach to optimize funding was outlined and overviewed. It was emphasized that the GSI is a work in progress and has already undergone several revisions since it was announced to the scientific community. Dr. Dieffenbach encouraged investigators to provide, and to keep providing, feedback to NIH.

HIV Clinical Trials Network Renewal

Dr. Dieffenbach spent the rest of his presentation discussing the next steps for the DAIDS Clinical Trials Networks which renew as initiatives in FY 2021. Every seven years the HIV Clinical Trials Network funding is competitively renewed at which time significant changes in research priorities that have evolved as a result of research progress can be addressed to create a forward-looking research agenda. NIH’s research priorities were outlined in August 2015 and include reducing incidence, developing and implementing a cure, improving the prevention and treatment of co-infections and co-morbidities, continuing to foster cross-cutting activities, like basic research, health disparities research, and training. Dr. Dieffenbach mentioned the commitment to retain the current tripartite structure of the leadership and operations center, laboratory center, and statistical and data management center; maintain the existing collaborations and foster new ones; and provide direct funding to clinical trials units and sites at a baseline level. With the re-competition, research will be focused on non-vaccine prevention, HIV vaccines, and therapeutics; questions across the life span including pediatrics and adolescents will drive research emphases; data interoperability and standardization to facilitate data sharing, exchange, and transparency will be implemented; and prioritized sharing of laboratory expertise across networks will be mandated. At this point in the process, DAIDS is continuing to request feedback. At the fall ARAC there will be a limited discussion, and then a full discussion with a formal presentation at the advisory committee meeting in the winter of 2017 or early 2018. After the winter meeting the initiatives will be written with awards to be made in November or December of 2020.

Discussion

Q: What differentiates an HVTN and an HPTN site? Both are trying to go into uninfected populations and prevent the acquisition of infection.

• These are different but special. A hybrid model could be considered when it comes to site activities where a set of standards for all networks would be used. Also, see the blog post regarding having a single prevention network that is on the DAIDS/NIAID website written by Dr. Dieffenbach. There are opportunities such as a matrix approach where groups could continue to talk across the three areas.

Q: What will be done to ensure the pediatrics’ voice gets heard?

• There have been profound successes in pediatrics. Hopefully groups can focus on critical questions in cures and TB. Adolescent prevention has not had appropriate attention in the current network structure. We need focused expertise in the area of vaccines and adolescent prevention and TB. There have been conversations with collaborators at the Eunice Kennedy Shriver National Institute of Child Health and Human Development that has been supportive of this model.

Office of AIDS Research Advisory Committee (OARAC) Update
Richard Chaisson, M.D., NIAID Advisory Council Representative to OARAC

Dr. Chaisson presented a report on the April 6^th OARAC meeting and briefly touched on several agenda items from that meeting. This included OAR activities for FY 2017, overarching high-priority areas, and version 3.0 of OAR which emphasized collaborations and partnerships across NIH institutes and across institutions and funding agencies nationally and globally. It was pointed out how critically important it is to accurately describe HIV across the life span in the United States. OAR will be forming working groups/task forces to tackle several HIV related issues to address challenges and priorities in HIV research. A DHHS panel retreat was planned for May 2017 covering several key issues on treatment: the substitution of TAF for TDF, the impact of boost Darunavir in cardiovascular disease, Dolutegravir side effects, and new drugs in the pipeline. Updates and revisions to adult and pediatric opportunistic infections guidelines and the pediatric guidelines were discussed. OAR held a community listening day and several major themes emerged. The remainder of the meeting addressed scientific issues including macrophage infection in HIV and the National Microbiome Initiative. A workshop on microphage infection and HIV was held in January 2017 which addressed the questions of the role of microphages in chronic infection and latency, and whether HIV persists in macrophages and does this drive inflammation and viral rebound. The workshop also discussed the Lung HIV Microbiome Project and gender differences in the microbiome and the effect on HIV transmission. The summary is that there is a lot of interest in HIV effects on the microbiome from infection acquisition, transmission, and prevention, and that more studies are needed. The OARAC meeting also discussed concerns that the GSI may be a disincentive to collaborations, partnerships, and large programs.

Discussion

Q: How much emphasis on microbiome is on bacteria versus virus fungi?

• Initial focus was on bacteria as it was easier and the viral microbiome is more challenging.

AIDS Vaccine Research Subcommittee (AVRS) Update
Aftab Ansari, Ph.D., AVRS Liaison and James Bradac, Ph.D.

Dr. Ansari presented a summary of the January 31, 2017 AVRS meeting that covered research updates from the two CHAVI-IDs, DAIDS Vaccine Research Program (VRP), and a special presentation. Accomplishments that the Duke CHAVI has made to overcome roadblocks for the development of a vaccine were discussed. These accomplishments included generating mosaic T cell immunogens from in silico homologous recombination to optimize CD4 and CD8 breadth and the mapping of co-evolution of transmitted/founder virus and the CD4 binding site bNAb. Dr. Ansari then discussed Duke CHAVI’s goal to design immunogens for testing in animals and eventually humans in coordination with HVTNs. Currently, Duke has six vaccines in manufacture. The Scripps CHAVI-ID outlined three different strategies, a trimer approach, a lineage presentation on trimers, and to use germline targeting, rational boosting, and trimer finishing, to accomplish their goal of designing an envelope-based vaccine to induce bNAbs with specificity for the CD4 binding site, the V3 glycan epitope, and the V2 apex epitope. Scripps has two vaccines that they are currently focusing on. It was emphasized that in the final two years of recurrent awards that the CHAVIs should try to prioritize studies since there are a number of different approaches for vaccine development and design.

Dr. Bradac summarized DAIDS VRP update at AVRS which covered grant programs and awards, vaccines in manufacture stage, and the clinical trial overview. Current ongoing clinical studies include the AMP and HVTN 702. The Ad26 trial, which was discussed at the Strategic Working Group Meeting the following day, is planned to begin in the latter part of 2017.

Discussion

[No questions]

Concepts Presented for Clearance

Basic Sciences Program (BSP)

Targeted In Vivo Delivery of Gene Therapeutics for HIV Cure
Betty Poon, Ph.D.

Dr. Poon presented the above titled proposed FY 2019 initiative which essentially had an objective to advance strategies to deliver anti-HIV therapies to target key cells in vivo. This is a new RFA for an R01, with an anticipated duration of five years. The first-year total cost would be $2.4 million. The number of awards is estimated to be five to six. This initiative is thought to be necessary at this time as previous strategies have been developed for ex vivo delivery of gene therapies and applicants could leverage the increase in knowledge of markers specific to latently infected cells to target HIV reservoirs in tissue sanctuaries. In vivo gene therapy, when compared with ex vivo approaches, would be minimally invasive, potentially more selective, less toxic, and avoid the current poor in vivo survival of ex vivo modified cells. An example of in vivo HIV gene therapy where CRISPR Cas9 was used to specifically target the HIV pro-virus in mouse models was given. The initiative is viewed as straddling basic research and translational research only and not clinical research. Applicants are expected to have a successful therapeutic approach with preliminary data at the time of submission. Exclusions include purely ex vivo studies that do not include an in vivo targeting delivery component, and discovery or development of new gene therapy payloads. The reviewers, Drs. Aftab Ansari and John Guatelli, recommended approval of the initiative. Reviewers’ comments were addressed and members voted.

Discussion

Q: Is it your sense that there are a lot of ideas how to achieve this goal that are not currently being funded, or is the goal of this to get people to think about this?

• Many approaches exist of in vivo delivery of gene therapeutics in different fields, including cancer and genetic diseases, and this initiative will bring that into the HIV field.

Q: Can you provide an example of an advance in vector targeting technologies that has been made?

• The Adeno-associated virus (AAV) tropism seems to be very broad and AAV tends to go to the liver. There’s been identification of AAV serotypes that are less liver specific and tend to target other cells, including hematopoietic stem cells. In terms of a non-viral vector delivery systems, there have been advances in nanoparticles that has been a broader area where engineers have designed a whole series of barcoded nanoparticles and looked in vivo to see whether you can identify a specific nanoparticle structure that would go to a tissue or other cell.

Comment: This is a huge area of investigation. Successful targeting with nanoparticles has either been topical or to the liver with salicylic protein to date. Targeting these cells with anti-HIV therapies will be tougher.

Comment: A lot of effort should be invested because it will be significant if it works as hoped and will enable many things. But, it may not be for people who want a quick return on their investment.

Q: To clarify, in the FOA you would like, similar in some U19s, to have a partner, such as a corporate partner. Would you stipulate that there had to be somebody who was an expert in this field?

• In the FOA, there would not be a mandate for a subject expert but areas of expertise that would be the best strategy would be emphasized. But there is some middle ground as this is an R01. Someone in a dual PI situation could be ideal.

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

Next Generation Biologics for Sustained HIV Remission
Brigitte Sanders, DVM, Ph.D.

Dr. Sanders presented an initiative to develop next generation, truly innovative biologics for HIV control. This is a new RFA and will utilize the R61/R33 phased award mechanism which provides for a two-year exploratory period, followed by an additional three-year period if pre-established milestones are met. The first-year total cost would be $2 million. The number of awards is estimated to be four to six. For background, Dr. Sanders reviewed the status of biologics under development for the treatment of HIV infection, including Ibalizumab, PRO-140, Vedolizumab and eCD4-Ig. Next generation biologics for HIV proposed for this initiative should address one or more of the well-known disadvantages of current antiviral treatment: life-long administration, daily dosing, chronic toxicity, lack of effect on the latent HIV reservoir, and failure to control rebound of virus after cessation of treatment. The objectives and scope will stress research innovation, not product development. Projects should evaluate next generation biologics in appropriate in vitro and in vivo models, develop analytical assays (pharmacokinetics and pharmacodynamics for example), and evaluate the new biologics for toxicity. Antibody engineering, stapled peptides and xenonucleic acids were given as examples of newer therapeutic approaches. Non-responsive areas of research include classic anti-HIV antibodies without major modifications, bacterial immunotoxins, gene therapy, purely descriptive basic research or structural studies, and clinical trials. The reviewers, Drs. Aftab Ansari and Cara Wilson, recommended approval of the initiative. Reviewers’ comments were addressed and members voted.

Discussion

[No questions]

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

NIH AIDS Reagent Program
Diane Lawrence, Ph.D.

Dr. Lawrence presented the NIH AIDS Reagent Program concept renewal with a purpose to provide access to high-quality, standardized biological and chemical reagents that are difficult to obtain and are essential for HIV/AIDS research. This initiative is an N01 contract with a duration of seven years. One award is anticipated. This program serves as a repository for a broad range of unique quality-assured reagents that are made available free of charge for the global HIV/AIDS research community. The scope of the proposed new contract would be to acquire, maintain, produce, expand, and distribute state-of-the-art standardized reagents for HIV/AIDS-related research to qualified investigators. The current reagent program inventory contains 2,593 unique reagents in the online catalog and the number of AIDS reagent program registrants has continued to rise since 2005. Several quality and efficiency improvements have been made such as shortened ordering and registration times, improved inventory tracking, and digital file management, but there are several planned improvements proposed for the next funding cycle including enhancing website functionality and catalog search features, developing a needs assessment survey for registered users, and streamlining inventory to focus on high-demand reagents and NIH HIV/AIDS research priorities. The reviewers, Drs. John Guatelli and Paul Bieniasz, recommended approval of the initiative. Reviewers’ comments were addressed and members voted.

Discussion

[No questions]

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

Therapeutics Research Program (TRP)

HIV Drug Resistance: Genotype-Phenotype-Outcome Correlations
Keith Crawford, Ph.D.

Dr. Crawford presented an initiative aimed to support studies that will evaluate HIV drug resistance and its relationship to treatment success. Applications are sought in areas to address genotype/phenotype/outcome correlations in non-B subtypes, to elucidate the role of minority variants in the development of resistance and virologic outcomes, and to improve understanding of why some drugs retain activity despite genotypic resistance. This is a new RFA for five-year R01 grants or two-year R21 grants. The first-year total cost would be $2.4 million and the number of awards is estimated to be four to five. The importance of the initiative was highlighted by the fact that acquired drug resistance and transmitted resistance have increased in both resource rich and limited settings. HIV drug resistance could compromise the WHO’s 90:90:90 target and the WHO’s predictions of almost 900,000 additional AIDS deaths in 15 years, almost 500,000 new HIV infections and additional ART delivery costs of $6.7 billion. The response to this involved a consultation on global trends in HIV drug resistance which identified several knowledge gaps. Dr. Crawford overviewed different types of drug resistance mutations and their impact on virus subtypes. The scope of proposed research would support projects that use specimens from well-characterized clinical cohorts for studies of genotype/phenotype/virologic outcome correlations across various clades/subtypes, studies of the role of minority variants across clades/subtypes and studies that focus on determining the biological basis for treatment success where genotype test results predict failure or treatment failure in the setting where resistance is not predicated by standard genotypic testing and adherence is thought to be optimal. This initiative will not support clinical trials, cost-effectiveness studies, studies focused primarily on adherence, and studies of resistance to neutralizing antibodies or other biologics. The reviewers, Drs. William Powderly and Sally Hodder, recommended approval of the initiative. Reviewers’ comments were addressed and members voted.

Discussion

Q: Is next generation sequencing going to be a requirement seeing as how the data shown appears to be more sensitive in detecting mutations?

• It will depend on what investigators propose. If the focus will be on minority variants, one of the accepted methods to look at next generation sequencing will be needed and then compared with the standard Sanger sequencing.

Q: Will you emphasize issues about viral fitness issues and how to measure that best in the context of the whole viral genome where there may be compensatory mutations and different genes?

• Yes, the concept of viral fitness is important in relation to drugs that may have activity even when there is resistance.

Comment: Pay attention to real virology, recognize the importance of the host genome and find the right cohorts. Only a handful of people have access to non-subtype B cohort specimens.

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

NIAID Virology Quality Assurance Program (VQA)
Joe Fitzgibbon, Ph.D.

Dr. Fitzgibbon summarized this VQA program renewal and described its purpose which is to serve a critical function in providing quality assurance and standardization of viral assays performed across clinical sites, allowing data to be combined for generalized interpretation and wide applicability of findings. This initiative is an N01 contract with a duration of seven years. One award is anticipated. The significance of this program ensures that clinical laboratories can generate accurate data that can be combined across clinical sites. The scope of research or resource outlined included implementing performance standards, evaluation studies, and obtaining all appropriate materials and reagents required for this work. Contract options for the renewal include support of additional laboratories, support of QA programs for assays of viral disease agents other than HIV and related co-infections, and support of late stage validation of assays and clinical testing in a CLIA certified laboratory. Contract accomplishments were listed and included a QA program that currently serves more than 100 DAIDS-supported or collaborative labs in 22 countries and an assay evaluation program that provided data on at least 15 different assays or methods currently in use or anticipated by the DAIDS clinical trial networks. This contract has also resulted in six journal articles, one book chapter, four manuscripts in preparation, and seven abstracts since 2012. The reviewers, Drs. Scott Hammer and Sharon Hillier, recommended approval of the initiative. Reviewers’ comments were addressed and members voted.

Discussion

Q: Regarding the decision between expanding the number of laboratories participating in the proficiency programs and balancing shipping samples and keeping them centralized. Could centralizing some assays be argued for?

• Many discussions have been had on this topic and the networks have to decide whether they need to add new labs or whether they can do things centrally. But, sometimes things cannot be done centrally because shipping is not available from certain countries. In those cases, a lab has to be brought into that country.

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

Halting TB Transmission in HIV Endemic Settings
Sudha Srinivasan, Ph.D., M.P.H.

Dr. Srinivasan presented the objectives of this initiative with the following aims: an improved understanding of the critical drivers of TB transmission, at the individual level and expanded to members of the Transmitter-Recipient Cluster Chains (TRCC) in HIV infected populations; the development of interventions to measure TB transmission at individual and community level and gaining a better understanding of the biomedical, environmental and population-based drivers of M. tuberculosis (M.tb) transmission in HIV endemic settings. This is a new R01, with an anticipated duration of five years. The first-year total cost would be $3.8 million. The number of awards is estimated to be three to five. The problems underlying the need for this initiative are that the TB is highly correlated with HIV prevalence, the disease incidence is driven by recent transmission rather than reactivation of latent infections, particularly in those HIV positive, and the impact of HIV treatment on TB transmission dynamics not being well understood. The response to the problem involved holding two NIAID/NIH workshops that sought to identify research gaps that will help develop novel interventions and strategies to halt TB transmission and specifically in HIV endemic settings. The scope of research would cover multi-disciplinary studies that characterize host/pathogen/micro-environment interactions that impact transmission in HIV endemic settings. This specifically includes the development and studies of new methods to measure transmission in various settings, host factors, the role of HIV in influencing transmission and effects of ART, elucidation of characteristics or subpopulations of M.tb strains inclusive of drug-resistant strains, and studies of nosocomial transmission and high-risk groups. This initiative will not support research proposals involving animal studies and trials of systemic chemoprophylaxis, host directed therapeutic agents or vaccines primarily intended to prevent progression from latent infection to active disease. The reviewers, Drs. Richard Chaisson and William Powderly, recommended approval of the initiative with modifications. Reviewers’ comments were addressed and members voted.

Discussion

Q: The U.S. government has spent a lot of money on aerosolized infectious diseases that would be intentional exposures and academia has also been involved with discovery. Could this information be used to answer aerobiology questions and could then lead to bringing in partners with experience in that area? 

• Aerobiology of TB has been extensively studied. Biodefense types of research may not contribute so much. What is driving TB transmission seems to be the key. Recent presentations at the South African workshop highlighted this where in one study, 70 percent of HIV-infected individuals, how TB transmission is unknown. Another study of 600 TB infected children in Soweto, and over half with HIV, showed 80 with no apparent source case. How does an 11-month-old get TB when there is no one known in the environment who is infected? This is an important question.
• Epidemiological and/or host factors would therefore probably be critical to be a response to this mechanism.
• There is a lot of work focused on genetic susceptibility to both infection and progression. But HIV trumps it all—adding HIV just washes out all of the biomarkers that would predict TB progression.

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

TRP and Prevention Sciences Program (PSP)

Understanding Immunopathogenesis of Tuberculosis in HIV-1 Infected and Exposed Children
Patrick Jean-Philippe, M.D.

Dr. Jean-Philippe presented the purpose of this initiative to support research to identify changes in immune mechanisms and markers in the context of M. tuberculosis (M.tb) exposure, infection or disease in pediatric populations exposed to or infected with HIV-1. This is a new RFA for a R01, with an anticipated duration of five years. The first-year total cost would be $3.8 million. The number of awards is estimated to be three to five. The rationale for this initiative is that the burden of TB remains high in children who account for 10 percent (1 million) of the WHO estimated 10.4 million new TB cases globally in 2015 with high mortality. Childhood TB is a different disease than adult TB and young age is a risk factor for TB-induced morbidity and mortality. Additionally, HIV further increases the high vulnerability to TB in young children and evidence for altered host-pathogen interaction as a cause of host vulnerability is emerging. The scope of research would support projects that involve study of biological specimen obtained from the target population in the setting of ongoing clinical trials, prospective cohorts or other clinical or research settings where the target population is followed; or study of stored blood/biologic samples from target population from well-characterized, well-maintained repositories; or studies using a non-human primate (NHP) pediatric model that recapitulates TB/HIV co-infection in the setting of immunologic immaturity setting. This initiative will not support non-target populations or stored samples from such populations when used as a primary focus of research, new clinical trials, or prospective cohorts, and research using non-NHP animal modes. Areas of interests include the role of immune mechanisms in pediatric TB and TB/HIV immunity and immune correlates and/or prognostic host markers of protection from TB infection or active diseases in M.tb exposed or infected children. The reviewers, Drs. Chris Wilson and Elizabeth McFarland, recommended approval of the initiative with modifications. Reviewers’ comments were addressed and members voted. 

Discussion

Q: Looking at the role of sex hormones in adolescents and comparing that to younger children, might be something that would be fitting for this RFA as it has not been well addressed in the past.

• Focus of this RFA is on younger children as there is an age cap on the population that is targeted. As written, such an evaluation of sex hormones might not be possible as this RFA targets children up to age 14 as we are interested in looking at immunologic maturity that comes with that age and obviously in the setting of HIV/TB co-infections.

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

VII. Adjournment

The meeting of the Council adjourned at 4:10 p.m., on Monday, June 5, 2017.

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.