NIAID Council Minutes: January 25, 2016

The 182nd meeting of the National Advisory Allergy and Infectious Diseases (NAAIDC) convened by teleconference on Monday, January 25, 2016. Dr. Anthony S. Fauci, director, National Institute of Allergy and Infectious Diseases (NIAID) provided recorded remarks for the open session.

In accordance with the provisions of Public Law 92-463, the open session of the meeting was held from 9:30 a.m. to 10:30 a.m. The closed session was held from 8:30 a.m. to 9:30 a.m. 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 Speaker—Eliseo J. Pérez-Stable, M.D., director, National Institute on Minority Health and Health Disparities
IV. Report of the Allergy, Immunology, and Transplantation Subcommittee—Daniel Rotrosen, M.D., director, DAIT
V. Report of the Microbiology and Infectious Diseases Subcommittee–Irene Glowinski, Ph.D., deputy 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 by teleconference in closed session to consider applications in allergy and immunology, microbiology and infectious diseases, and AIDS.

Funding Actions: The Council reviewed 4,352 research and training applications with primary assignment to NIAID for a requested amount of $1,651,369,649 in first-year direct costs and recommended approval of 2,152 applications with $699,336,144 in first-year direct costs.

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

Dr. Fauci provided his remarks to council via a video recording. He introduced six new Council members: Dr. Raul Andino, University of California, San Francisco; Dr. Aftab Ansari, Emory University; Dr. Wendy Book, Emory University; Dr. Sally Hodder, West Virginia University; Dr. Karen Nelson, J. Craig Venter Institute; and Dr. Cara Wilson, University of Colorado at Denver.

He also welcomed ad hoc Council member, Dr. Mark Feinberg, president and CEO of the International AIDS Vaccine Initiative.

Staff and Organizational Changes

In September, Dr. Michael Lauer was appointed NIH deputy director for extramural research, filling the vacancy left by Dr. Sally Rockey.

Dr. Carole Heilman, who has served as Division of Microbiology and Infectious Diseases (DMID) director since 1999 and managed a complex national and international research program in infectious diseases, will retire in February. Dr. Irene Glowinski, who has been DMID’s deputy director since 2007, will serve as acting director until a new director is selected.

In October, Dr. Ernie Takafuji, director of the Office of Biodefense Research, retired from federal service. A search is currently underway for a director of the newly restructured Office of Biodefense Research and Surety.

Tributes and Awards

Dr. Cliff Lane, deputy director for clinical research and special projects and director of the Division of Clinical Research, received the 2015 Distinguished Achievement Award from the University of Michigan Medical Center Alumni Society.

Dr. David Morens, senior scientific advisor in NIAID’s Office of the Director, was elected as a fellow of the American Society of Tropical Medicine and Hygiene.

The American Society of Tropical Medicine and Hygiene awarded Dr. Peter Crompton, chief of the Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, the Bailey K. Ashford Medal for distinguished work in tropical medicine by a midcareer professional.

Mike Tartakovsky, director of NIAID’s Office of Cyber Infrastructure and Computational Biology, received a 2015 Meritorious Executive Rank Award, one of two categories of Presidential Rank Awards.

Meetings and Events

In September, a delegation from the Brazilian Ministry of Health visited NIAID’s Vaccine Research Center (VRC) and received an overview of VRC research with a focus on respiratory syncytial virus and chikungunya vaccines.

On October 16, a Korean delegation, including Dr. Jooshil Lee, director of the Korean National Institute of Health, visited NIH. During the visit, Dr. Francis Collins signed a broad letter of intent with the Korean NIH to collaborate and interact with NIH on the Precision Medicine Initiative and Middle East respiratory syndrome coronavirus.

On October 30, three members of a scientific delegation from Cuba visited NIH. All members of the delegation were featured speakers of the symposium “Cuba-U.S.: Building Bridges Through Science and Global Health.” The meeting served as an opportunity to meet Cuban colleagues and identify mutual interests and priorities.

On November 9, Dr. Fauci participated in a panel discussion “U.S. National Security Benefits From Global Health,” during a meeting at the Bipartisan Policy Center Conference on Strategic Health Diplomacy. He discussed the origins and success of the President’s Emergency Plan for AIDS Relief (PEPFAR).

On November 19, Dr. Fauci delivered a TEDMED talk describing how in the early years of the HIV/AIDS epidemic he chose to embrace flexibility in conducting research to advance science while addressing the urgent needs of people with HIV/AIDS.

In December, Ambassador-at-Large Dr. Deborah Birx gave the 2015 Joseph J. Kinyoun Memorial Lecture. She described how the use of data gathered by PEPFAR has been critical for understanding local HIV prevalence, determining the quality and cost of services, and defining key gaps.

On December 16, NIH released its 2016-2020 Strategic Plan, “Turning Discovery Into Health.” The Plan describes key objectives and identifies goals for the next five years.

On January 11, Dr. Fauci delivered a keynote presentation at the 18th International Conference on Emerging Infectious Diseases in the Pacific Rim.” The Conference was part of an NIH-organized event commemorating the 50th Anniversary of the U.S.-Japan Cooperative Medical Sciences Program.

Budget Update

The President’s Budget for Fiscal Year 2017 is expected to be released on February 9.

The President recently signed the FY 2016 omnibus spending bill that allocates $32.2 billion for NIH.

NIH received an increase of 6.6 percent in the FY 2016 enacted budget, with institute increases ranging from 3.9 percent to 33.4 percent. The variation is a result of earmarks. NIAID received an earmark of $100 million for antimicrobial resistance research in support of the President’s Combating Antibiotic-Resistant Bacteria Initiative.

Our financial management plan for FY 2016 is similar to FY 2015 but it expands our R01 paylines to the 13th percentile for established investigators and the 17th percentile for new investigators. Support for competing NIAID program initiatives remains at levels that were previously cut by up to 10 percent to sustain investigator-initiated awards. Funds for R56-Bridge and selective pay awards will be unchanged from previous years. NIAID plans an increase for its extramural research portfolio of 6.8 percent over FY 2015 and a 4 percent increase for intramural research.

Legislative Update

Rep. John Boehner, Speaker of the House, resigned from Congress effective October 31, 2015. Rep. Paul Ryan was elected on October 29 as his replacement.

On November 5, Dr. Fauci participated in a briefing in Washington, DC, on “Fast-Tracking the End of AIDS,” and discussed the scientific progress and evidence that makes achieving epidemiologic control and ending the AIDS pandemic feasible goals.

On November 17, Dr. Fauci briefed staff to the Senate and House appropriations and authorizing committees on progress toward developing universal flu and HIV vaccines and updated them on NIH’s Ebola research.

Also in November, Dr. Carole Heilman briefed bipartisan staff of the House Energy and Commerce Committee, Subcommittee on Oversight and Investigations, on NIAID’s influenza research program. She then testified at the November 19 Subcommittee hearing about U.S. public health preparedness for seasonal influenza.

Dr. Fauci provided an update on congressional efforts to develop legislation aimed at advancing medical research and innovation.

Other Information Items

Dr. Fauci began with an update on Ebola, presenting the latest statistics on reported cases and deaths. He summarized the status of the three PREVAIL (Partnership for Research on Ebola Virus in Liberia) trials—a vaccine trial, a treatment trial, and a survivor natural history trial.

For the PREVAIL I vaccine trial, the immunogenicity analysis and follow-up are expected to conclude in May 2016.

The PREVAIL II treatment trial closed in January 2016 after enrolling 72 participants, and the data is being analyzed.

As of January 20, 2016, the PREVAIL III survivor natural history trial had enrolled 1,811 people (1,023 survivors and 788 contacts).

Dr. Fauci continued with HIV/AIDS items of interest, which included CDC findings about a lack of awareness and use of pre-exposure prophylaxis, an initiative to develop long-acting HIV treatment and prevention tools, and several recent articles in the New England Journal of Medicine. He also summarized three antiretroviral treatment (ART) studies that show the benefit of early and continuous ART.

He concluded by giving updates of the mosquito-borne diseases dengue, chikungunya, and Zika; multidrug-resistant tuberculosis; and seasonal influenza vaccine.

III. Guest Speaker—Eliseo J. Pérez-Stable, M.D., director, National Institute on Minority Health and Health Disparities

Dr. Eliseo J. Pérez-Stable presenting his remarks via video recording began by giving a brief history of the National Institute on Minority Health and Health Disparities (NIMHD). NIMHD was established as an Office in 1990, then transitioned to a Center in 2000, and through the Patient Protection and Affordable Care Act became an Institute in 2010. Dr. Pérez-Stable was named NIMHD director on September 1, 2015.

NIMHD’s mission is to lead scientific research that advances understanding of minority health and health disparities. One of Dr. Pérez-Stable’s priorities for 2016 is to coordinate and lead the development of a trans-NIH Health Disparities Strategic Plan.

He described NIMHD’s strategy to advance the science of health disparities, defined minority health and health disparities, and provided a list of minority health and health disparity populations. Dr. Pérez-Stable also explained the differences in outcomes or events that indicate a health disparity.

He outlined some strategies for minority health and health disparities research activities, gave some examples of disparities issues in immunological and infectious diseases, and listed his other priorities as NIMHD director.

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

Dr. Rotrosen welcomed the subcommittee members to the 182nd meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting.

Dr. Rotrosen presented the following new staff members, and scientific and division activities:

Staff and Organizational Changes

Lisa Wheatley, M.D., M.P.H. Dr. Wheatley was selected as chief of the Asthma and Airway Biology Section in the Allergy, Asthma, and Airway Biology Branch in December 2015. She received her medical degree from Loyola University/Stritch School of Medicine and her public health degree from the University of Massachusetts, Amherst. She completed her allergy and clinical immunology training at the University of Pennsylvania and was an assistant professor at the University of Virginia. Prior to joining DAIT, she was in private practice and participated in pharmaceutical research trials as a principal investigator. Dr. Wheatley joined DAIT in July 2012 as a medical officer in the Food Allergy, Atopic Dermatitis, and Allergic Mechanisms Section.

Scientific Initiatives

Notice of NIAID's Participation in RFA-HL-16-003 "Collaborative Projects to Accelerate Research in Organ Fibrosis (R01)" (NOT-AI-16-013): The purpose of this notice is to inform potential applicants of the NIAID’s participation, effective immediately, in the funding opportunity announcement (FOA) RFA-HL-16-003, entitled "Collaborative Projects to Accelerate Research in Organ Fibrosis (R01)."

Human Immunology Project Consortium (U19) (RFA-AI-15-041): This FOA on the Human Immunology Project Consortium solicits applications from single institutions, or consortia of institutions, to participate in a network of human immunology profiling research groups in the area of infectious diseases, including HIV. The purpose of this FOA is to characterize human immune responses/mechanisms elicited by vaccinations, adjuvants, or natural infection by capitalizing on recent advances in immune profiling technologies.

Development of Radiation/Nuclear Medical Countermeasures or Biodosimetry Devices (BAA-NIAID-DAIT-NIHAI2015042): The purpose of the broad agency announcement (BAA) is to advance the development of candidate medical countermeasures (MCM) or biodosimetry biomarkers/devices to assess and reduce mortality and/or major morbidities associated with exposure to radiation from a radiological or nuclear incident.

Environmental Influences on Child Health Outcomes (ECHO) Data Analysis Center (U24) (RFA-OD-16-005): The purpose of this FOA is to support a Data Analysis Center (DAC) for the Environmental Influences on Child Health Outcomes program. The ECHO DAC will provide the data repository and the data analysis functions for all common ECHO activities.

Environmental Influences on Child Health Outcomes (ECHO) Coordinating Center (U2C) (RFA-OD-16-006): The purpose of this FOA is to support a Coordinating Center for the Environmental Influences on Child Health Outcomes program. The ECHO Coordinating Center will provide the organizational framework for the management, direction, and overall coordination of all common ECHO activities.

U.S.-China Program for Biomedical Collaborative Research (R01) (RFA-AI-16-006): The purpose of the U.S.-China Program for Biomedical Collaborative Research is to stimulate collaborative basic, translational, and clinical research between U.S.-based researchers and Chinese researchers in the areas of allergy, immunology, and infectious diseases including HIV/AIDS and its co-morbidities and co-infections, mental health, and selected neurological disorders.

Characterization of Mycobacterial Induced Immunity in HIV-Infected and Uninfected Individuals (R21) (PAR-15-360): The purpose of this FOA is to support hypothesis-generating research on innate and adaptive immune responses induced by mycobacterial infection, Bacillus Calmette-Guérin vaccine (BCG), or other Mycobacterium tuberculosis (Mtb) vaccinations. A secondary objective of this FOA is development of new assays and technologies enabling comparison of mycobacterial-specific mucosal and systemic immunological pathways in HIV-infected or uninfected individuals that can be used to monitor immune responses in preclinical studies and vaccine trials to advance Mtb vaccine development.

Request for Information (RFI): Input on NIAID Data Sharing Repository, Immunology Database and Analysis Portal (ImmPort), and Services (NOT-AI-15-045): NIAID’s Division of Allergy, Immunology, and Transplantation is seeking input from the research community with expertise and interest in public data repository management and services.

Division Activities

Allergy, Asthma, and Airway Biology Branch

2015 Annual Asthma and Allergic Disease Cooperative Research Center Face-to-Face Meeting (AADCRC). On November 3 and 4, 2015, NIAID sponsored the 10th annual face-to-face meeting of the AADCRC investigators in Rockville, MD. The one and a half day meeting of PIs, co-investigators, students, and program staff included oral and poster presentations from the 11 NIAID-funded research centers, a special session featuring the work of AADCRC-funded young investigators, and fostered data-sharing and collaboration between centers.

Basic Immunology Branch

Modeling Immunity for Biodefense. On October 1, 2015, the meeting of Modeling Immunity for Biodefense was held in Rockville, MD. During the meeting, investigators provided updates on the computational models of immunology to better understand and study the immune response to infection or vaccination. Four U19 grants funded in May 2015 are using influenza infection and/or vaccination in their research. The scientific meeting was followed by a brief steering committee meeting to discuss integration between centers, the formation of a scientific advisory group, the Infrastructure and Opportunity fund, and scheduling of future symposia and summer schools.

Immune Epitope Database and Analysis Workshop. On October 28 and 29, 2015, staff from the DAIT-supported Immune Epitope Database and Analysis program (IEDB: www.iedb.org) held a training workshop in Rockville, MD. The workshop included participants from academic, industry, and government backgrounds. Attendees learned how to use the analysis tools present on the IEDB website as well as how to search the highly curated IEDB itself. The training involved practical exercises as well as lectures. Feedback from 2015 participants has been very positive and attendance higher than in previous years of the IEDB program. The workshop was one component of outreach from the IEDB program and was successful.

Adjuvant Discovery and Adjuvant Development Annual Meeting. On November 2 to 4, 2015, the first joint meeting of the FY 2014 NIAID Adjuvant Discovery and FY 2013 Adjuvant Development contractors was held in Rockville, MD. Keynote speakers, Drs. Karen Messer (University of California San Diego) and Gregory Sempowski (Duke University) presented talks to introduce novel bioinformatic tools to the contract groups. The principal investigators of seven adjuvant discovery contracts presented their recent findings, including high-throughput screening approaches used to identify adjuvant candidates and elucidate their mechanisms of action. The principal investigators of the four adjuvant development contracts presented an overview of their progress during the second year of award.

Human Immunology Project Consortium II (HIPC II) Kick-Off meeting. On November 18 and 19, 2015, the meeting of the HIPC research network was convened in Rockville, MD. The HIPC program is focused on defining, analyzing, and correlating molecular profiles of varied human immune responses induced by infection or vaccination, as a way to help define the human immune system and its responses to antigen exposure. The Steering Committee participated in the November meeting together with other HIPC investigators and NIAID staff. Each of the three HIPC II centers introduced their research programs, and the group discussed methods to advance/promote human immunology research, including the public release in January 2016 of ImmuneSpace (https://www.immunespace.org/), a powerful data management and analysis engine for the exploration and analysis of HIPC-generated datasets using state-of-the-art computational tools.

Cooperative Centers on Human Immunology. On December 1 and 2, 2015, the annual meeting of the Cooperative Centers on Human Immunology was held in Rockville, MD. Six U19 grants were funded in 2014 to support hypothesis-testing, mechanistic studies on the activation and regulation of human immune responses in the context of infectious disease. The goal of the annual meeting is to facilitate communication and collaboration among program investigators. The PIs of short discretionary fund projects as well as investigators involved in parent grant projects summarized their accomplishments from the first year.

Autoimmunity and Mucosal Immunology Branch

Cooperative Study Group for Autoimmune Disease Prevention. On October 19 and 20, 2015,the annual meeting of the Cooperative Study Group for Autoimmune Disease Prevention (CSGADP) was held in Rockville, MD. The mission of this program is to engage in scientific discovery that significantly advances knowledge for the prevention and regulation of autoimmune disease. During the meeting, the group’s principal investigators presented recent highlights from their projects in type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. On the second day, the group heard and discussed reports from outside investigators who were awarded funding from the CSGADP for pilot studies in autoimmune disease prevention as well as for a collaborative project that seeks to elucidate the dynamics of autoantibody repertoires across several autoimmune diseases via a coordinated analysis of different subject cohorts. Proposals for new pilot studies were also reviewed and approved by the Steering Committee.

Radiation and Nuclear Countermeasures Program (RNCP)

NIAID Workshop on Exploration of Radiation Injury to Endothelial Cells and the Vasculature: Identification of Mitigators and Treatments. On August 20, 2015, the RNCP held a workshop in Rockville, MD. The goal of the workshop was to better understand the role of the endovascular system in radiation injury. Discussions were focused on elucidation of the role of the endovascular system in multi-organ dysfunction that occurs following radiation exposure. Gaps were identified in the understanding of mechanisms of endovascular radiation-induced injury and how these injuries contribute to overall mortality following radiation exposure. Targets for mitigation and potential countermeasure candidates were also discussed.

NIAID Workshop on Medical Management for the Gastrointestinal Acute Radiation Syndrome. On September 20, 2015, RNCP held a workshop in Weston, FL. The goal of the workshop was to exchange ideas from various institutions on their procedures used for medical management of the GI-syndrome. Various options were discussed in the context of feasibility, concept of operations, and best outcomes. A follow-up meeting to be cosponsored with the Radiation Injury Treatment Network is planned for the summer of 2016.

NIAID/BARDA Radiation Portfolio Update Meetings. On September 25, 2015 (biodosimetry portfolio) and November 5 (medical countermeasures portfolio), update meetings were held between the RNCP and Biomedical Advanced Research and Development Authority (BARDA) staff. The purpose of these meetings, requested by the HHS assistant secretary of preparedness and response, was to provide programmatic transparency, ensure that the funded research programs are aligned, provide advanced information on potential transition of promising candidates, and ensure that there is no scientific overlap between the two product research and development portfolios.

Kickoff Meeting for Contract HHSN272201500013I. On October 5, 2015, NIAID held a meeting in Rockville, MD for the RNCP Product Support Service Contract with SRI, International. This contract was established to support product development for the RNCP. At this meeting, NIAID’s contracts procedures and the capabilities of SRI were presented. Plans for the first year’s activities as well as procedures for fulfilling the terms specified in the statement of work were also discussed.

NIAID Biodosimetry Program Review. On October 26 and 27, 2015, the RNCP organized a biodosimetry workshop in Rockville, MD in order to better understand the current status of biodosimetry in the field of radiation research as well as to showcase all biodosimetry studies funded by the NIAID. Needs/requirements of different government funding were re-defined, and the pathways to FDA licensure were discussed. Recent advances and achievements in the field were highlighted, and obstacles in tissue-specific biodosimetry, as well as transitioning to the human experience, were considered.

NIAID/FDA Scientific Forum #8 on Medical Management of Patients in a Radiation Public Health Emergency Incident. On November 3, 2015, NIAID staff from both the RNCP and the Office of Regulatory Affairs, NIAID/DAIT, convened a scientific meeting in White Oak, MD. FDA attendees included personnel from both review and liaison divisions from the Center for Drugs Evaluation and Research and the Center for Devices for Radiological Health. Speakers presented subject matter pertinent to the management of radiation injuries, both in humans and in surrogate animal models.

Concepts Presented for Clearance

FY 2017 Research Concept Clearances

Systems Approach to Immunity and Inflammation: The primary objective of the program is to develop a comprehensive understanding of innate and adaptive immune responses to pathogens or vaccines using a systems biology approach. The initiative will support quantitative analyses by interdisciplinary teams that identify and measure dynamic networks regulating such immune responses. The basis of the research program will be genome-wide screens of mutant mice for identification of key regulatory immune response genes. Unbiased approaches, such as a forward genetics screen, are preferred, although more targeted high-throughput methods may be utilized with adequate justification. The studies will be complemented by detailed genomics, proteomics, computational biology, and bioinformatics approaches to identify mechanisms of immune regulation. This initiative will lead to a better understanding of immune response dynamics following challenge and will provide detailed information for translational approaches in the discovery and development of vaccines and immunotherapeutics.

The subcommittee endorsed and unanimously approved this initiative.

Nonhuman Primate Transplantation Tolerance Cooperative Study Group: Competitively renew the Nonhuman Primate Transplantation Tolerance Cooperative Study Group (NHPCSG). The NHPCSG is a multi-institution consortium, whose goals are to identify and develop novel therapeutic and donor-specific tolerance induction regimens, refine existing regimens, evaluate the preclinical efficacy of the candidate regimens, and elucidate the underlying mechanisms of the induction, maintenance, and/or loss of tolerance in NHP models of pancreatic islet, kidney, heart, and lung transplantation.

The subcommittee endorsed and unanimously approved this initiative.

Maintenance of NIAID Specific Pathogen-Free Macaque Breeding Colonies: This initiative will continue support of the maintenance, care, and breeding of the NIAID-owned Indian rhesus macaque (Macca mulatta) and cynomolgus macaque (Macca fascicularis) specific pathogen-free (SPF) breeding colonies. These colonies provide SPF macaques of known pedigree and MHC to the NIAID and NIDDK cosponsored Nonhuman Primate Transplantation Tolerance Cooperative Study Group, which conducts preclinical immune tolerance research in solid organ and pancreatic β islet cell transplantation.

The subcommittee endorsed and unanimously approved this initiative.

Emerging Science and Technologies in Transplantation Research: The goal of this initiative is to promote the application of emerging science and technologies to transplantation immunology. It will encourage and stimulate transplantation immunology research in three priority areas: 1) microbiota and alloimmunity; 2) targeted therapeutic delivery; and 3) in vivo imaging. These three research fields have seen exciting progress in recent years, but application of these advances to transplantation immunology has been slow. This initiative will accelerate progress in these areas and support advances in transplantation immunology through the development and application of new scientific advances and technologies and the formation of new interdisciplinary collaborations. The application of these advances to the field of transplantation will provide valuable insights into the fundamental understanding of alloimmune responses and reveal new avenues to prevent rejection and prolong graft survival.

The subcommittee endorsed and unanimously approved this initiative.

V. Report of the Microbiology and Infectious Diseases Subcommittee–Irene Glowinski, Ph.D., deputy director, DMID

Director’s Report

Dr. Irene Glowinski, deputy director of the Division of Microbiology and Infectious Diseases (DMID), chaired the NIAID Microbiology and Infectious Diseases Council Subcommittee meeting on January 25, 2016; Director Carole Heilman was out of the country on work-related business. Dr. Glowinski introduced two new members to the DMID Subcommittee, Dr. Karen Nelson, president of the J. Craig Venter Institute (JCVI), and Dr.Raul Andino, a professor of microbiology and immunology at the University of California, San Francisco, where he specializes in RNA viruses. She also recognized Dr. Mark Feinberg, who participated as an ad hoc member; he was recently appointed as the president and CEO of the International AIDS Vaccine Initiative, and has extensive experience advancing scientific and public health policy initiatives that focus on the prevention and treatment of a wide variety of infectious diseases.

Following introductions, Dr. Glowinski presented four proposed DMID topics for inclusion in the FY 2017 NIH/CDC SBIR Omnibus Contract Solicitation:

• Rapid Point-of-Care Diagnostics to Detect Serologic Status of Individuals for Select Viral Infections
• Development of Microbiome-Based Products for Infectious Diseases
• Noninvasive Rapid Diagnostics for Respiratory Diseases in Children
• Phage-Based Diagnostic Platforms for Rapid Detection of Bacterial Pathogens

Dr. Glowinski briefly described the scientific and programmatic significance of these topics, the availability and feasibility of proposed technologies associated with each, and noted the potential uses of the intended end product under each area. The Subcommittee approved all four topics.

Finally, on behalf of NIAID’s Division of Clinical Research (DCR), Dr. Glowinski made a motion to accept a report generated by a working group of Council concerning a DCR concept clearance for “Scientific and Administrative Management and Operations Support Services” at the High Containment Integrated Research Facility at Fort Detrick, Frederick, MD. Related materials were posted in the Electronic Council Book for the Subcommittee’s information. The motion to accept the report was approved.

Program, Scientific, and Budget Updates

None.

Concepts Presented for Clearance

The following fiscal year 2017 concepts were presented to the Subcommittee:

Human Tissue Models for Infectious Diseases – Dr. Melody Mills, a program officer in DMID’s Enteric and Hepatic Diseases Branch, presented this concept to the Subcommittee. The objective is to adapt bioengineering (especially tissue engineering) methodologies to develop in vitro models that mimic biological structures, recapitulate human physiology/pathology, and incorporate components critical to infectious disease and human host response for evaluation of the human disease process as well as new candidate products. The DMID Human Tissue Models for Infectious Diseases (HTMID) concept was praised for its critical importance to the field of infectious diseases research. One Subcommittee member stated that this was the most important concept he had reviewed since joining the DMID Subcommittee, noting that it was central to moving the infectious disease field forward, given the difficulty in developing in vitro and animal models. The concept would help to advance the development of in vitro model systems that mimic human pathophysiology to provide relevant predictive outcomes for human infectious diseases; it would support multidisciplinary, integrated research approaches that advance understanding of infectious diseases through overcoming obstacles that inhibit basic science and product development. One Subcommittee member noted that the concept narrative seemed focused on drugs, but Dr. Mills clarified that the intent was to be broad and encompass vaccines as well; the concept was meant, albeit in the very long term, to address product development in general. Another Subcommittee member cited the importance of basic science studies that could be conducted under this concept. Subcommittee members asked about the proposed U19 mechanism. Dr. Mills pointed out that the U19 mechanism was one of several possible mechanisms that would be considered during development of the initiative. The concept was approved unanimously with accolades for its significance and importance to the field of infectious disease research.

Partnerships for Structure-Based Design of Novel Immunogens for Vaccine Development – Dr. Paula Bryant, senior scientific officer in DMID’s Office of Biodefense, Research Resources, and Translational Research, presented this concept. The objective is to utilize novel, structure-based vaccine design approaches to generate candidate vaccine immunogens effective against infectious disease pathogens. The Subcommittee was enthusiastic about this new Partnerships concept to elicit multidisciplinary research efforts focused on using 3D structural information to design new and improved vaccine immunogens. The Subcommittee recognized that recent technical advances in areas such as structural and computational biology, along with proof-of-principle data for structure-based vaccine design, position this strategy as one that is now ready to be exploited for hard-to-target pathogens of interest. One member noted that to ensure success, efforts should not be limited to a single antigen and/or broadly neutralizing antibodies. The concept was unanimously approved.

Advanced Development of Multivalent Vaccine Candidates for Filovirus and Lassa Fever – Dr. Larry Wolfraim, a project officer in DMID’s Office of Biodefense, Research Resources, and Translational Research, presented this concept to the Subcommittee. The objective is to advance the development of promising multivalent vaccines against filoviruses (Ebola, Sudan, and Marburg) and Lassa Fever. The concept was well received by the DMID Subcommittee as they acknowledged its timeliness and utility. Subcommittee members raised concerns pertaining to the potential regulatory challenges associated with multivalent vaccines when the immune correlates of protection are unknown and inquired about the potential duplication of efforts across agencies. It was pointed out that strides are being made regarding a number of immune correlates of protection, much of the data is unreported, and that preclinical efficacy data on bivalent vaccines for Ebola and Lassa have been published. Furthermore, licensure of any multivalent filovirus vaccine, in the absence of a large outbreak, would likely follow the FDA Animal Rule, which DMID has significant experience navigating. The Filovirus Animal and Nonclinical Group (FANG), an interdepartmental and interagency group, was referenced as a resource where guidance regarding potential regulatory challenges can be discussed with the FDA. In addition, the FANG allows for coordination between various U.S. government agencies to avoid duplication of efforts. Lastly, the Subcommittee suggested that, in terms of regulatory pathways, it may be more productive to focus on developing monovalent vaccines. It was noted that many of the current multivalent vaccines use monovalent vectors and that the unpredictable nature of viral hemorrhagic fever outbreaks, both where they occur and the responsible etiologic agent, emphasizes the need for a multivalent vaccine. The concept was unanimously approved.

The meeting was adjourned at 10:24 a.m.

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

The AIDS Research Advisory Committee (ARAC) participated in a teleconference on Monday, January 25, 2016, from 9:30 a.m. to 10:40 a.m.

Participating voting members: Stephen W. Mason (Chair), Aftab Ansari, Amanda Castel, John Guatelli, Scott Hammer, Sharon L. Hillier, Sally Hodder, David O’Connor, Deborah Persaud, William G. Powderly, Cara Wilson, and Chris Wilson. Voting member missing: Ernest C. Hopkins. Ex officio members: Victoria J. Davey, Robert Eisinger, and Jonathan Mermin. Ex officio members missing: Henry Masur, Colonel Nelson Michael. DAIDS Representatives: Carl Dieffenbach, Emily Erbelding, Mary Marovich, Sarah Read, Diana Finzi, Manizhe Payton, Sheryl Zwerski, Carol Worrell, Peter Kim, Dale Hu, Alan Embry, Cesar Boggiano, Tony Conley, Stephen Smiley, Carla Pettinelli, Daniella Livnat, Brigitte Sanders, Joe Fitzgibbon, Pamela Gilden, Martin Gutierrez. Mark Mueller served as executive secretary. Others present: Roy Gulick (OARAC Liaison) and court reporter.

Welcome and Approval of Minutes

Stephen Mason, Ph.D., Chair, ARAC

Dr. Mason welcomed everyone.

Dr. Dieffenbach welcomed everyone to this abbreviated ARAC teleconference/meeting and pointed out that traditionally the January ARAC meeting is the opportunity to set the research agenda for the year and to look at the previous fiscal year with a report card. He explained that these will not be put forward at this time, but that Mark Mueller will see that these Council presentations are on the Portal and that these include the grant funding report card for the past fiscal year. Not surprisingly, given the fact that NIAID/DAIDS had a slight budget increase, there was a slight improvement in overall success rate. He said that Dr. Fauci will post the State of the Institute remarks detailing how the increased budget for 2016 will play out for NIAID and DAIDS (Link:NIAID Advisory Council - January 2016). Dr. Dieffenbach explained that the concepts being put forward at this meeting are solicitations in critical areas in which DAIDS is trying to accelerate research.

Concepts Presented for Clearance

SBIR Contract Topics

Dr. Dieffenbach explained that the SBIR program is a Congressionally-mandated set-aside that is growing by 0.5 percent of the budget for this FY.

Topic 1: Simplified Sequencing for TB Drug Resistance Testing

Project goal: to develop a low-cost, easy-to-use platform for TB drug resistance testing and surveillance for settings with high HIV prevalence and limited laboratory resources.
Phase I activities:

• Develop a technique allowing simultaneous sequencing from a single sputum sample (patient sample or spiked) of at least 40 key genes and genetic regions associated with resistance to tuberculosis drugs

Phase II activities:

• Refine technique to generate accurate sequencing data on first-line and second-line drugs from single smear-negative culture positive sputum sample
• Develop a self-contained device for settings with limited laboratory resources, and incorporate:
  • Simple operation, requiring few steps performed by operator
  • No need for external electricity (battery power can be proposed)
  • Total running time must be three hours or less per sample
  • Software that will interpret data to provide immediate clear results for susceptibility to TB drugs with no need for clinician interpretation
  • Ability to upload sequencing data to central data repository

Guidelines:

• Direct to Phase II applications will not be accepted
• Fast Track applications will be accepted
• Number of anticipated awards: 1 to 2
• Budget (total costs): Phase I: $300,000 per year for up to two years; Phase II: $1,000,000 per year for up to three years

Discussion

Q: How many of the drugs listed in Phase I have overlapping resistance profiles?
A: We are aiming for the first and second-line drugs, so there is not much overlap in resistance between the drugs. There is some overlap with fluoroquinolones and erythromycins. We picked the 40 genes because we thought that would cover all of the major first and second-line classes with at least 80 percent to 90 percent specificity of the resistance.

Q: My comment was that if one has figured out all of Phase I activities, then the first bullet of Phase II is not that far from having that already worked out. So the first bullet in Phase II should actually be in Phase I. The difficult part is going to be developing the self-contained device.
Q: In regard to HIV drug resistance testing, which has been automated for several years, do we have a similar device that can do this? And what sort of timeframe are you expecting from Phase I to Phase II?
A: The total timeframe for Phase I through Phase II is up to four years. Currently, there is one machine available for HIV drug resistance. The goal is not necessarily to follow the same path with TB that HIV went. We are trying to help the TB community leap over the intermediate technology into a more advanced technology by putting this type of plan forward. As you know, MDR TB in HIV-infected kids is going to be a big issue. Making sure we can get this built and pushed toward pediatrics is going to be important for us.

Ballots were marked and sent to Mark Mueller.

Recommendation:
12 Approval
0 Approval with modification(s)
0 Deferral for further information
0 Disapproval

Topic 2: Effective Targeted Delivery of RNA-Based Vaccines and Therapeutics

The primary goal of this contract solicitation is to encourage small businesses to develop improved platform technologies for the delivery of RNA into specific cells and tissues to improve the efficacy of HIV vaccines or therapeutics. The short-term goal is to perform feasibility studies for the development and use of delivery mechanisms for RNA-based HIV vaccines and therapies. The long-term goal is to enable a small business to bring fully developed delivery systems for RNA-based HIV vaccines and therapies to the clinic and eventually to the market.

Guidelines:

• Direct to Phase II applications will not be accepted
• Fast Track applications will be accepted
• Number of anticipated awards: 1 to 2
• Budget (total costs): Phase I: $300,000 for up to one year; Phase II: $2,000,000 for up to three years

Discussion

Q: We at the Gates Foundation agree that the formulation issue has been under-addressed. There is a lot of exuberance in the venture capital community for this type of approach. Formulation appears to be one of the key barriers. We endorse the idea of sourcing new ideas through SBIR.
A: As you can see from our Phase I activities, we are stressing the delivery component through exosome nanoparticles, liposomes, and other ways of capturing and targeting it to the appropriate cells. This is essential. It is not just about stabilizing the message. The technology is fairly well worked out. It is now about effective targeted delivery of these RNA-based vaccines and therapeutics.

Ballots were marked and sent to Mark Mueller.

Recommendation:
12 Approval
0 Approval with modification(s)
0 Deferral for further information
0 Disapproval

Topic 3: Qualitative HIV RNA Home Test

Project goal: to develop a method for HIV RNA home testing.
Phase I activities may include:

• Development of simple methods for: a) obtaining finger-stick blood and easily transferring blood to the test medium, b) detecting HIV plasma RNA, but not cell- associated HIV DNA, with a cutoff of 1,000 RNA copies per mL of blood, c) providing an easily readable output
• Combining the methods into an inexpensive, easy-to-use, integrated assay platform (up to $100 for handheld unit, up to $10 per test unit/cartridge)
• Initial testing on laboratory isolated, including several HIV subtypes

Phase II activities may include:

• Validation testing to include sensitivity, specificity and lower limit of detection, with comparison to FDA-approved HIV viral load test methods
• Development of a well-defined test platform under good manufacturing practices (GMP)
• Development of a quality control program to ensure lot-to-lot consistency
• Scale-up and production for multi-site evaluations using clinical isolates

Guidelines:

• Direct to Phase II proposals will not be accepted
• Fast Track proposals will be accepted
• Number of anticipated awards: 1 to 2
• Budget (total costs): Phase I: up to $300,000 for up to one year; Phase II: up to $3,000,000 for up to three years

Discussion

Q: Was any thought given to use of oral secretions?
A: Oral is better for antibodies. Because this is targeted specifically at RNA, we want to stick with blood because we want to detect the virus itself, not the Ab response.

Q: Is there a specific reason you restricted this to RNA, rather than a protein like p24?
A: In spite of all the work that Evergreen and others have done in this area, p24 has not delivered on detecting acute infection early. So we wanted to stimulate innovation by looking at RNA. Investigators could apply for a grant to do work on p24. That would be an unsolicited SBIR and would be completely acceptable. But for a contract, we want to stick with RNA.

Q: Are you thinking this would be done independently so people would do the testing themselves, correct?
A: That is one option, but also this could be easily a POC screening at a clinic or a doctor’s office. Someone who came in with flu-like symptoms could get a quick screen, like a rapid test for strep. There would be plenty of options for such a kit.

Ballots were marked and sent to Mark Mueller.

Recommendation:
11 Approval
1 Approval with modification(s)
0 Deferral for further information
0 Disapproval

Comment:

• If testing is to be done independently, DAIDS may want to ask Phase II applicants to include transfer of results to a provider to ensure data are available to act upon.

Therapeutics Research Program (TRP)

Optimization of Monoclonal Antibodies (mAb) for Eliminating the HIV Reservoir (R01) ‒ Presented by Dr. Stephen Smiley

This initiative will support the optimization of mAb or mAb derivatives that recognize and eliminate the HIV reservoir. HIV-targeting mAb and mAb derivatives within the scope of this initiative are:

• Broadly neutralizing mAb
• Non-neutralizing mAb
• Bispecific mAb
• Multi-specific mAb
• mAb conjugated to other proteins, peptides, or compounds

Dr. Smiley explained that this is a new R01 initiative with a duration of awards for five years. It has yet to be determined if there will be set-aside funds for this initiative. The estimated number of awards is two to three. He said that optimization may include Fc and/or Fab modifications that increase potency of killing or otherwise eliminating infected cells, breadth of strain recognition, and barriers to viral escape. Also, optimization should aim to increase half-life, biodistribution and stability, with no increase in immunogenicity. Studies should include analyses of cross-reactivity to human adult and fetal tissue, preliminary assessments of pharmacokinetics, and efficacy in appropriate animal models. DAIDS expects that at the end of five years several mAb, or mAb derivatives, optimized for eliminating the HIV reservoir will be ready for further advancement toward manufacturing for human testing.

Discussion

Q: Thousands of these antibodies have been made already. Should not the emphasis be on setting up an assay system to screen the antibodies properly for eliminating reservoir?
A: Yes. As part of this initiative, we expect that they will put forward hypotheses about what types of activities each molecule should show in vitro or in preclinical animal model assay systems, and then identify the best candidates using those systems.

Q: Do we have an assay in vivo or in vitro that tells us that there is a good approach to eliminating reservoirs?
A: The field has not yet settled on a specific assay that will unequivocally demonstrate reservoir reduction that translates to humans. Mouse models have shown some efficacy. One could identify the best antibodies in those models (empirically or otherwise), determine which ones work best, and then try to understand why they work best and build upon them. Our plan is to allow the study section to evaluate the models, and then the program would oversee that and judge whether we think these are proper assessments.

Ballots were marked and sent to Mark Mueller.

Recommendation:
11 Approval
1 Approval with modification(s)
0 Deferral for further information
0 Disapproval

Comment:

• Assays utilized to reduce viral reservoirs are the key to this concept proposal and should be emphasized in the RFA.

Mechanisms of Mycobacterial-Induced Immunity in HIV-Infected and Uninfected Individuals to Inform Tuberculosis Vaccine Design (R01) ‒ Presented by Dr. César Boggiano

The objective of this initiative is to encourage applications to characterize the innate and adaptive immune responses induced by mycobacterial infections and/or Bacillus Calmette-Guerin (BCG) vaccine or candidate anti-Mycobacterium tuberculosis (Mtb) vaccines in HIV-infected or uninfected individuals. DAIDS encourages:

• Studies that will provide insights into the immune mechanisms required for protection from Mtb infection/re-infection or progression to active disease in latently-infected individuals
• Studies that elucidate the differential responses in HIV-infected and HIV-uninfected individuals
• Research approaches that go beyond descriptive information currently known about Mtb infection and responses to vaccines, immune modulation by nontuberculous mycobacterial (NTM) infection and/or HIV/AIDS
• Applications that propose characterization of the timing, anatomical location, and contribution to disease outcome of systemic and/or mucosal immune responses to Mtb infection and/or vaccination. Such studies may include but are not limited to:
  • Understanding how Mtb subverts cellular processes and/or the immune function to establish primary and/or latent infection
  • Identification and analysis of immune responses elicited during Mtb infection in either HIV-infected or HIV-uninfected people, including:
    • Immune responses that may benefit mycobacterial persistence
    • Innate immune pathways and mechanisms, such as the effect of Mtb infection on innate immune cell function and downstream activation of adaptive immune responses
    • Mucosal and systemic adaptive immune responses, including signaling networks and regulatory mechanisms of mycobacterial infection/disease
• Elucidation of mechanisms (host or pathogen) responsible for transition to active TB disease in susceptible individuals and how HIV infection may shift this balance
• Effect of prior/chronic exposure to nontuberculous mycobacteria or BCG vaccination or other candidate Mtb vaccines on subsequent immune responses to Mtb infection, TB reactivation, or disease reoccurrence in HIV-infected or HIV-uninfected individuals
• Effect of Mtb or related mycobacteria infection of thymic epithelial cells on local or systemic host immune responses to Mtb infection or candidate vaccines, such as the induction of immune tolerance to mycobacterial antigens
• Determine how protective immune cells can be mobilized to, and maintained in, the lung
• The contribution of the humoral immune response to protection against Mtb or immune evasion by Mtb
• Determine the mechanisms governing Mtb-induced decoy immune responses and their implications for vaccine design
• Investigate the timing/nature of immune responses leading to protection against disseminated TB in children to determine whether activity of BCG can be modified to protect against Mtb infection or disease in adults
• The role and subversion of lymphatic functions in the response against Mtb, to include aspects such as immune cell trafficking through the lymphatic system or lymphangiogenesis in the dissemination of Mtb and alterations in these functions that might occur in HIV-infected persons

Discussion

Q: How are you going to assure that this probes new areas and uses relevant models, like the SIV model in macaques, as opposed to investigators continuing to do the usual mouse model work?
A: We are addressing that by making this initiative a special-emphasis study section, not general, and by emphasizing innovation with the FOA and review criteria.

Q: The initiative as written is broad and diffuse. Where this initiative stands in the NIAID portfolio needs to be made clearer. Is it towards vaccine development, new therapeutics, immunotherapeutics, pathogenesis, new approaches to TB research?
A: This initiative represents the output from all three extramural divisions (DAIDS, DAIT, DMID), so we are trying to come up with a comprehensive set of strategies. The three divisions will work together to address critical aspects so we can ensure that the vaccine designs will work in HIV-positive people. This is a new way of looking at research across NIAID.

Ballots were marked and sent to Mark Mueller.

Recommendation:
9 Approval
3 Approval with modification(s)
0 Deferral for further information
0 Disapproval

Silencing of HIV-1 Proviruses (R61/R33) ‒ Presented by Dr. Tony Conley

The objective of this new initiative is to support research to identify new small-molecule or RNA agents with novel mechanisms of action to mediate epigenetic silencing of HIV-1 integrated proviruses. The hope is that the new agents will establish long-term (lifetime) silencing of the HIV proviruses with the need for continuous administration. This initiative will use milestone-driven, bi-phasic awards to support preclinical research teams to validate cellular targets in a silencing pathway where redirection, agonism, or antagonism leads to sustained silencing of HIV-1 proviruses; to perform screening for small-molecule compound or RNA leads; and to carry out medicinal chemistry for optimization of physical characteristics of lead compounds.

Phase 1 (R61) will support hypothesis-driven target validation and development of the drug- screen methods. Phase 2 (R33) will support the screening activities. Each project will meet mutually-established milestones and criteria for go/no go decision to transition to the R33 award. Dr. Conley explained that the initiative will complement cure studies ongoing within DAIDS-funded Collaboratories. It will complement the Beyond HAART program projects and some grants in the HIV persistence area. The proposed studies meet the DAIDS priority of development of long-acting therapies and fit within the cure agenda. Dr. Conley emphasized that set-aside funding will be necessary to motivate potential applicants, due to the risk associated with assay setup, validation, and compound screening. This initiative is an outgrowth of the NIH Common Fund Epigenomics Program that included complementary epigenomics initiatives aimed at generating new research tools, technologies, datasets, and infrastructure that are available to support the approaches proposed in this initiative.

Discussion

Q: How would one know whether such silencing is permanent?
A: We will address that in the initiative language. It is a very difficult question because there can be a variety of loci where the proviruses can exist. Some may be amenable to silencing, and some may not. The key element will be specificity. If the agent that is developed recognizes sequences within proviruses, as long as those sequences are recognizable in a variety of environments, then we might expect to see success. Another approach to this, from a screening perspective, is to identify different environments in which to place or to find a provirus. We could screen for a molecule that could work on the more difficult, as well as the easier, one.

Ballots were marked and sent to Mark Mueller.

Recommendation:
11 Approval
1 Approval with modification(s)
0 Deferral for further information
0 Disapproval

Comment:

• The emphasis on induction of heterochromatin formation when HIV integration is most likely in active genes needs to be modified.

VII. Adjournment

The meeting of the Council adjourned at 10:40 a.m., on Monday, January 25, 2016.

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.