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NIH National Advisory Allergy and Infectious Diseases Council

Minutes of Meeting: September 19, 2011

The 169th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened at 10:30 a.m. on Monday, September 19, 2011, 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 10:30 a.m. to 11:40 a.m. and from 1:00 p.m. to 4:00 p.m. The meeting was closed to the public from 8:30 a.m. to 10:15 a.m. and from 11:40 a.m. to 12:00 p.m. for review and consideration of individual grant applications. Notice of the meeting was published in the Federal Register.

Council Members Present:

  • Dr. Ann Arvin
  • Dr. Carol Carter
  • Dr. Connie Celum
  • Dr. Nelson Chao
  • Ms. Dázon Diallo
  • Dr. Michael Holtzman
  • Mr. William McLin
  • Dr. Louis Picker
  • Dr. Regina Rabinovich
  • Dr. Velma Scantlebury
  • Dr. Samuel Stanley
  • Dr. Jenny Ting
  • Dr. Christel Uittenbogaart
  • Dr. Jerome Zack

Ex Officio Members Present:

  • Dr. Victoria Davey
  • Dr. Anthony Fauci
  • Dr. Bruce Gellin
  • COL Kent Kester
  • Dr. Rima Khabbaz

Ad Hoc Member Present:

  • Dr. Bernhard Hering

Ex Officio Members Absent:

  • MG James Gilman

Council Members Absent:

  • Dr. Norma Kenyon
  • Dr. George Siber
  • Dr. Christopher Walker
  • Dr. Richard Whitley

NIAID Senior Staff Present:

  • Dr. Hugh Auchincloss
  • Dr. Carl Dieffenbach
  • Dr. Carole Heilman
  • Dr. Clifford Lane
  • Dr. Marvin Kalt
  • Dr. John McGowan
  • Dr. Daniel Rotrosen

Table of Contents

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 2,529 research and training applications with primary assignment
to NIAID for a requested amount of $869,711,869 in first-year direct costs and recommended approval of
574 applications for $186,008,357 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 also welcomed Dr. Velma Scantlebury, Christiana Care Transplant Center, to her first Council meeting. Dr. Fauci introduced one ad hoc Council member, Dr. Bernhard Hering, University of Minnesota, and noted that Colonel Kent Kester, the Department of Defense representative on the DMID subcommittee, moved from Walter Reed to the Uniformed Services University of the Health Sciences.

Five Council members, Drs. Kenyon, Siber, Walker, and Whitley and Major General James Gilman were unable to attend the meeting.

Dr. Fauci acknowledged the contributions of five retiring Council members -- Drs. Ann Arvin, Carol Carter, Louis Picker, Regina Rabinovich, and Christel Uittenbogaart -- and presented them with plaques, certificates, and letters of appreciation for their service. 

Consideration of Minutes of Previous Meeting

Council considered the minutes of the May 23, 2011, meeting and approved them as written.

Staff and Organizational Changes

Dr. Steven Holland is the new NIH deputy director for Intramural Clinical Research. He will also continue as chief, Laboratory of Clinical and Infectious Diseases, Division of Intramural Research, NIAID.

In DMID, Dr. Fred Cassels was named chief of the Enteric and Hepatic Diseases Branch.

In June, Ms. Pamela Gilden joined DAIDS as chief of the Science Planning and Operations Branch. Ms. Sandra Whalen was selected as chief of the Workforce Development Branch, Office of Workforce Effectiveness and Research.

Dr. Fauci announced that Dr. Marvin Kalt, director, Division of Extramural Activities, will be retiring at the end of the year and was attending his last Council meeting. He also noted that Dr. Antonio Scarpa recently retired as director of the NIH Center for Scientific Review (CSR). Dr. Richard Nakamura will serve as acting director of CSR until NIH recruits a new director.

Tributes and Awards

Dr. Fauci paid tribute to three people who recently passed away and whose lives were important to biomedical research and to NIH in particular – Dr. Bernadine Healy who was director of NIH from 1991 to 1993, Dr. Baruj Benacerraf who was one of the outstanding immunologists of his era and received the 1980 Nobel Prize in Physiology or Medicine, and U.S. Senator Mark Hatfield who was a strong supporter of biomedical research and made possible the NIH Clinical Research Center that bears his name.

Dr. William Paul celebrated his 40-year anniversary as chief of NIAID’s Laboratory of Immunology. Dr. Paul is an NIH Distinguished Investigator and is best known for his work on cytokine biology.

Dr. Fauci recognized Drs. Thomas Quinn, Connie Celum, and Kuan-Teh Jeang for awards they have received. He also congratulated Drs. Ronald Germain, Steven Holland, and Alan Sher for being named NIH Distinguished Investigators.

Dr. Fauci announced that the NIH Clinical Center received the 2011 Lasker-Bloomberg Public Service Award for serving as a model institution that has transformed scientific advances into innovative therapies and provided high-quality care to patients. 

In August, Dr. Fauci visited NIAID’s Rocky Mountain Laboratories in Hamilton, Montana, and delivered a public lecture, “Thirty Years of HIV/AIDS: A Personal Journey.” 

Meetings and Events

Dr. Fauci gave the State of the Science Address at the Pacific Health Summit which was held in Seattle from June 21 to 23.

In August, Dr. Fauci visited NIAID’s Rocky Mountain Laboratories in Hamilton, Montana, and delivered a public lecture, “Thirty Years of HIV/AIDS: A Personal Journey.”

Dr. Fauci reminded Council about changes under consideration to enhance standards of protection for human subjects who participate in research studies. HHS is seeking public comments on the proposed changes and has extended the comment period to October 26, 2011. 

Budget Update 

In February, the President submitted the FY 2012 President’s Budget to Congress. For NIH he requested a 3.5 percent increase over FY 2011 and an increase of between 2.5 and 3.0 percent for the major institutes. Since then, other events have occurred that will have a significant impact on budgets and programs throughout the government.

In August, Congress passed and the President signed a bill to raise the U.S. government’s debt ceiling limit. A critical part of the bill included language that enforces a set of processes to significantly reduce the long-range deficits and debt of the U.S. government, which is also expected to affect NIAID. 

Congress continues to debate the budget and FY 2012 appropriations. We expect to be facing significant fiscal challenges that will need to be addressed over the next several years.

Legislative Update 

On July 26, Dr. Fauci addressed the American Foundation for AIDS Research (amfAR) at its 2011 Capitol Hill Summit conference entitled, “Making AIDS History: Ending the Epidemic.”

In August, a staff delegation of the Senate Labor-HHS Appropriations Subcommittee visited NIH- and CDC-supported research sites in India and Cambodia. Mr. Gray Handley, NIAID associate director for international research affairs, and Dr. Thomas Frieden, director of CDC, represented NIH and CDC respectively.

Other Information Items 

September 11 marked the ten-year anniversary of the terrorist events in New York, Washington, D.C., and Pennsylvania. Soon after the 9/11 attacks, the infamous anthrax attacks occurred through the mail. Dr. Fauci gave an overview of how these events generated a considerable amount of activity to get the country ready for a possible bioterrorist attack. He summarized some of NIAID’s accomplishments over the last ten years and gave examples of research programs and resources that the Institute developed to respond to a bioterrorist attack and emerging and reemerging infectious diseases.

This past summer marked the 30-year anniversary of the recognition of AIDS as a new syndrome. On May 31, Dr. Fauci gave a lecture at NIH entitled “30 Years of HIV/AIDS: A Personal Journey.” He summarized advances in the areas of HIV/AIDS treatment and prevention. 

III. Guest Speaker—Kathryn Zoon, Ph.D., Director, Division of Intramural Research, National Institute of Allergy and Infectious Diseases

Dr. Zoon presented strategic priorities for the Division of Intramural Research (DIR) for FY 2012 and 2013, which included stabilizing the portfolio of basic research in infectious diseases and immunology with a declining budget; supporting translational and clinical research; succession planning of senior investigators and recruiting new tenure track investigators; and pursuing mission-related CRADAs, licensing agreements, and other partnerships.

To deal with budget reductions over the next two fiscal years, DIR plans to reduce the number of laboratories and principal investigators; consolidate administrative processes and reduce personnel costs; apply salary caps and freezes; and reduce the costs of support contracts, clinical research, equipment, and travel.

Dr. Zoon announced three personnel changes, including one newly tenured investigator, one new tenure-track investigator, and one retirement. She also recognized a number of DIR scientists who have received distinguished honors and awards.

The Board of Scientific Counselors performed its peer review of DIR laboratories. All the labs reviewed received a rating of outstanding.

Dr. Zoon concluded with an overview of DIR’s research programs. Dr. Byron Caughey developed a prion-based blood test which should be helpful in detecting variant Creutzfeldt-Jakob disease and also for blood screening. Other areas she highlighted were influenza and malaria. 

IV. Report of the Division of Allergy, Immunology, and Transplantation Council Subcommittee—Daniel Rotrosen, M.D., Director

Dr. Rotrosen welcomed new and returning members to the National Advisory Allergy and Infectious Diseases Council Subcommittee meeting. Dr. Rotrosen began his presentation by announcing new staff members: Dr. Wendy Davidson as a program officer in the Asthma, Allergy, and Inflammation Branch and Ms. Gail Wolfson as a public health analyst in the Office of Program Planning, Operations, and Scientific Information.

Dr. Rotrosen next took the opportunity to inform the subcommittee members that it was a great pleasure to have Dr. Bernhard Hering, Professor of Surgery and Medicine, Department of Surgery, University of Minnesota present an “Interim Progress Report on Licensure of a New Cellular Therapy for Clinical Islet Transplantation.” He noted that before we hear Dr. Hering’s presentation, Dr. Nancy Bridges, chief, Transplantation Immunobiology Branch would discuss “The Clinical Islet Transplant Consortium” and it’s “Collaboration in Support of Licensure of a New Cellular Therapy.”

Following the presentations, Dr. Rotrosen informed the Council members there were four concepts for their review and approval. 

The following concepts were presented for the Subcommittee’s consideration: 

Radiological/Nuclear Medical Countermeasure Product Development: This initiative is to provide funds to continue and expand non-clinical efforts for product development of radiological/nuclear medical countermeasures effective for the mitigation or treatment of acute radiation syndromes, radionuclide decorporation agents to treat internal contamination, and radiation biodosimetry products for inclusion in the Strategic National Stockpile for potential use during a radiological emergency. The Subcommittee unanimously approved this initiative. 

Gastrointestinal Acute Radiation Syndrome Medical Countermeasures Development: This initiative is to support investigator-initiated proposals for the continued development of new mitigators/therapeutics (or improvement of existing drugs) to treat or mitigate the lethal effects of gastrointestinal radiation exposure due to a nuclear or radiation incident. Radiation exposure type, dose level, and dose rates proposed for study would be those that would be relevant following a terrorist incident or accidental exposure. The Subcommittee unanimously approved this initiative. 

Post-Exposure Mitigation/Treatment of Radiation Injury: The purpose of this initiative is to support investigator-initiated applications across a broad range of topics, ranging from investigations into the mechanisms of radiation-induced cellular and organ injury mitigation to the development of new mitigators/therapeutics (or improvement of existing drugs) to address the short- and long-term effects of radiation exposure. Radiation exposure type, dose level, and dose rates proposed for study would be those that would be relevant to a terrorist incident or accidental exposure. The Subcommittee unanimously approved this initiative.

Investigations on Primary Immunodeficiency Diseases: The primary objective of this initiative is to encourage Research Project Grant (R01) applications that propose investigations in primary immunodeficiency diseases focusing on ex vivo studies with human specimens and on studies with current or new animal models including novel clinical strategies for detecting, identifying the molecular basis of, or developing innovative therapies for primary immunodeficiency diseases. The Subcommittee unanimously approved this initiative. 

V. Report of the Division of Microbiology and Infectious Diseases—Carole Heilman, Ph.D., Director

After welcoming the Subcommittee, Dr. Heilman acknowledged two Subcommittee members who would be retiring after today’s meeting, Drs. Regina Rabinovich and Ann Arvin, and thanked them for their service. She then turned to DMID personnel issues and noted the recent appointment of Dr. Fred Cassels as Chief of the Enteric and Hepatic Diseases Branch, and referred to the Branch Chiefs in attendance to introduce their respective new hires.

After welcoming the Subcommittee, Dr. Heilman acknowledged two Subcommittee members who would be retiring after today’s meeting, Drs. Regina Rabinovich and Ann Arvin, and thanked them for their service. She then turned to DMID personnel issues and noted the recent appointment of Dr. Fred Cassels as chief of the Enteric and Hepatic Diseases Branch, and referred to the branch chiefs in attendance to introduce their respective new hires. 

Request for Applications (RFA). The Web site briefly outlines the general structure of the new program, and describes the resources and requirements that may be applicable to the program. Subcommittee members were encouraged to visit the new Web site (on the NIAID home page at: http://www.niaid.nih.gov/about/organization/dmid/clinical/Pages/leadership.aspx).

Dr. Heilman also noted that DMID would hold a Town Hall Meeting on November 1, 2011, to engage the research community in early discussions regarding the evolution of the NIAID Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases (RCE) Program (information available at: https://respond.niaid.nih.gov/conferences/rce2011/Pages/default.aspx).

Finally, Dr. Heilman noted two upcoming DMID program reviews. First, in October, DMID will convene an external review group to assess the accomplishments of the Centers of Excellence for Influenza Research and Surveillance, a program established in 2007 and poised for renewal in 2014. In December, DMID will convene an external review group to assess DMID’s international research portfolio, which spans all branches and offices in DMID. A member of the Subcommittee is serving on each review body, and they will report back to the Subcommittee on the outcome of these respective program reviews at a subsequent Council meeting.

Influenza Update 

Following Dr. Heilman’s opening remarks, Dr. David Spiro, section chief of the Influenza, SARS and Related Viral Respiratory Diseases Section in DMID’s Respiratory Diseases Branch, provided an overview of DMID’s current influenza research program. He described current research efforts and resources that support the influenza program, e.g., in vitro antiviral screening; shared scientific success stories that have come out of the program over the past ten years, particularly DMID’s response to the 2009 H1N1 pandemic; and outlined future research directions, noting recent publications that promise to have a significant impact on the future of the field.

DMID Concept Clearances

The following three concepts were presented to the Subcommittee for their review and approval:

Concept Clearance: Partnerships for Development of Therapeutics and Diagnostics for Biodefense. The objective of this concept is to support the development of therapeutic and diagnostic candidate products against NIAID Category A-C agents for which proof of principle has been established. The Subcommittee strongly endorsed the continuation of the DMID Biodefense Partnerships Program, noting that the program plays an important role in the Institute’s translational research activities. One Subcommittee member expressed concern about potential overlap between translational research programs at NIAID and the Department of Defense (DOD). Program staff detailed communication lines between DMID and relevant departments/agencies to coordinate efforts and prevent redundant activities. The Subcommittee favored the requirement for substantive investment by an industrial partner in R01 Partnership projects, and encouraged continued programmatic evaluation of program metrics. The concept was unanimously approved. 

Concept Clearance: Partnerships for Development of Vaccine Technologies. The objective of this concept is to develop innovative technologies that improve delivery, stability, and/or efficacy of vaccines. The Subcommittee was very enthusiastic about this initiative, noting that improved vaccine technologies would have an inherently broad impact both domestically and globally. The Subcommittee strongly supported the approach of enabling applicants to pair a candidate technology with an appropriately mature, well-characterized vaccine/antigen for which models and assays exist to allow evaluation of the technology; there was agreement that this approach would encourage new participation by key vaccine technology researchers and industries. The concept was unanimously approved.

Concept Clearance: Partnerships for Interventions to Treat Chronic, Persistent, and Latent Infections. The objective of this initiative is to develop novel intervention strategies to treat persistent, chronic, and/or latent infections. The Subcommittee was enthusiastic about this initiative, recognizing the urgent need to improve our ability to treat chronic, persistent, and latent infections and clear them from the host. One Subcommittee member suggested NIAID consider a term other than “candidate” to describe the stage of development of the compound being proposed either at the time of application or at the end of the R21 phase because the term “candidate” generally refers to a product further downstream along the product development pipeline (this concept targets very early product development activities). This same member suggested “testable intervention” as a possible alternative. Another Subcommittee member asked if pharma/biotech partners were required; they will not be. The Subcommittee unanimously approved the concept. 

VI. Joint Meeting of the AIDS Subcommittee, National Advisory Allergy and Infectious Diseases Council and AIDS Research Advisory Committee (ARAC)—Carl Dieffenbach, Ph.D., Director, DAIDS

Welcome and Approval of Minutes

Dr. Christel Uittenbogaart, chair, welcomed the ARAC members, DAIDS representatives, and guests. She presented the minutes of the May 23, 2011, ARAC meeting, and the members approved them without changes by a hand vote.

Director's Report

Carl W. Dieffenbach, Ph.D., Director, DAIDS 

Dr. Carl Dieffenbach welcomed everyone in attendance and extended a special welcome to Dr. Mary Young, an invited guest speaker, who has been a Principal Investigator with the Women’s Interagency HIV Study (WIHS) site in the District of Columbia since follow-up of the cohort began in 1993.

Dr. Dieffenbach acknowledged and thanked Drs. Carter, Picker, and Uittenbogaart, who rotate off the NIAID Council and ARAC after this meeting.

Dr. Connie Celum was congratulated as recipient of an Achievement Award from the American Sexually Transmitted Diseases Association (ASTDA) in recognition of her many significant contributions to research on STDs.

With regard to organizational updates, Mary Owens retired earlier this year from her post of Chief for the Scientific Planning and Operations Branch in the Office of the Director. Pam Gilden, who has more than 20 years of experience in program administration and policy, is taking over from Ms. Owens.

Budget Update 

Dr. Dieffenbach provided an overview of the NIAID budget. NIH and NIAID each received a budget cut of about one percent in fiscal year (FY) 2011, which was the first cut to the NIAID budget in more than 35 years. President Obama submitted the FY 2012 President’s Budget to Congress last February, requesting an increase in the FY 2012 budget of nearly three percent for NIH. However, the economy and other events have overtaken the budget process with significant impact on government programs for FY 2012 and beyond.

In early August, the President signed into law the Budget Control Act (BCA) of 2011, commonly known as the deficit-reduction package, to raise the U.S. Government’s debt ceiling limit and trim at least $2.1 trillion from the Government’s budget over a 10-year period. Although it is unclear how elements of the BCA will affect NIAID in FY2012 and beyond, the automatic spending reduction process will cap and cut expenditures at a very broad level. On September 20, 2011, the Senate Appropriations Labor-HHS Subcommittee is scheduled to mark up the NIH’s FY 2012 appropriations bill. The House has not yet scheduled its markup. Dr. Dieffenbach suggested that a conversation about specific actions with regard to cuts be postponed until the February meeting. 

Scientific Highlights

Data released in July from a landmark study, Partners PrEP (pre-exposure prophylaxis) funded by the Bill and Melinda Gates Foundation, demonstrated that a daily dose of an antiretroviral drug was highly effective at preventing HIV in both men and women. In findings from another study – TDF2 conducted by the Centers for Disease Control and Prevention (CDC) trial – PrEP was also found to reduce the risk of HIV infection among heterosexuals. Dr. Dieffenbach noted the “ladder effect” on efficacy success, proceeding sequentially from the FEM-PrEP trial with no impact on HIV prevention through the HPTN 052 which showed a reduction of 96 percent on HIV acquisition with ARV treatment. The challenge is how to integrate the trial success of medical interventions into comprehensive prevention packages.

The HIV Vaccine Trials Network (HVTN) 505, funded by NIH and launched in 2009, is a Phase 2, proof-of-concept study that uses a prime-boost strategy of two investigational vaccines developed by NIAID’s Vaccine Research Center (VRC). When the study was initiated, the primary endpoint was to determine if the prime boost vaccine can significantly decrease the amount of virus (viral load) in individuals who have become infected with HIV. However, the study is being expanded to include prevention of HIV acquisition as another primary endpoint. Initially, the thought was that neutralizing antibodies were required to prevent acquisition. However, the Thai trial (RV144) and similar vaccines tested in non-human primates have since demonstrated that protection against HIV acquisition can occur without neutralizing antibodies. As a result, enrollment has been increased to 2,200, which will enable the study to assess whether the vaccine regimen is at least 50 percent effective in preventing acquisition during the first 18 months following immunizations.

In the two years since the RV144 results were first presented, researchers led by Dr. Barton Haynes, have conducted a search for correlates of protection to help explain the 31 percent efficacy and guide future research. For the correlates analysis of 41 HIV-infected vaccinees, 205 uninfected vaccinees, and 40 placebo recipients, the researchers measured six primary immunological variables: binding IgA antibodies in plasma; IgG avidity to A244 gp120 ( the antigen used in the vaccine candidates); antibody-dependent cell cytotoxicity (ADCC); neutralizing antibodies; binding IgG antibodies to the V1/V2 loops of HIV envelope (Envs) scaffold onto a gp70 from murine leukemia virus; and CD4 T-cell responses expressing at least one of several designated cytokines (e.g., interferon gamma, interleukin-2).

The findings of the RV144 correlate analysis raised two key hypotheses: 1) vaccine-induced V2 antibodies capable of binding a conformational V1, V2 construct appear to correlate with lower risk of infection; and 2) vaccine-induced plasma IgA responses to a panel of 14 Envs associate with increased infection rate when compared within the vaccinated group. The limitations of the correlates search (for instance no mucosal samples were collected in the RV144 trial and small sample amounts) mean that the findings cannot provide absolute correlates of protection, but rather provide direction for new studies to validate or disprove the correlates of risk predicted by the post-hoc case-control study. Additionally, future studies are needed to identify the immune mechanisms underlying the correlates and to determine if the correlates are generalized enough for use in the design of new vaccines.

A partnership of public and private entities has been formed to build on the RV144 results through clinical development of pox-prime protein boost concepts in trials in higher incidence populations. The collaboration is known as the Pox-Protein Public Private Partnership (P5). The goals of this partnership are to extend and confirm the RV144 efficacy results and develop a strategy to translate the findings into a potentially licensable product.

Two awards were made this summer as part of the Consortia for AIDS Vaccine Research in Nonhuman Primates and will allow the researchers to explore early response to infection in macaques. The awards totaling about $12 million per year for up to five years were granted to Eric Hunter at Emory University (Atlanta, GA), and to co-investigators, Dan Barouch and Paul Johnson at Beth Israel Deaconess Medical Center (Boston, MA).

The information and insights gleaned from the macaque studies will be used to develop human HIV vaccine candidates capable of blocking infection, preventing the establishment of late HIV infection, or significantly reducing the effects of infection.

NIAID recently made three grant awards under the Martin Delaney Collaboratory to foster public-private partnerships to accelerate progress towards a cure ($14 million per year for up to five years). The awards went to: The Fred Hutchinson Cancer Research Center & Sangamo Biosciences (Keith Jerome and Hans-Peter Kiem); University of North Carolina at Chapel Hill & Merck (David Margolis); and University of California San Francisco and the Vaccine & Gene Therapy Institute & Merck (Steven Deeks, Mike McCune, and Rafick-Pierre Sekaly).

The Strategic Working Group (SWG) has been reorganized. In January 2012 the SWG and AIDS Vaccine Research Subcommittee (AVRS) will meet jointly and then will alternate meetings in the future according to the following schedule: 

  • January 31- February 1, 2012 (joint meeting)
  • May 15-16, 2012 (AVRS)
  • September 25-26, 2012 (SWG)
  • February 5-6, 2013 (AVRS)
  • May 21-22, 2013 (SWG)
  • September 17-18, 2013 (AVRS)

Update: AIDS Vaccine Research Subcommittee (AVRS) 

James A. Bradac, Ph.D., Chief, Preclinical Research and Development Branch
Vaccine and Prevention Research Program, NIAID, DAIDS

Dr. Bradac gave a summary of the February and May, 2011 AVRS meetings. The February meeting included talks about the HIV vaccine strategy and activities of the Gates Foundation. The meeting also encompassed a workshop on the HIV vaccine pipeline and a discussion of RV144 follow-up. The May meeting centered on the novel adenovirus vector workshop and addressed the pros and cons of the vectors as a class. Dr. Bradac noted that in the future the AVRS will have a role in coordinating the information between the preclinical and clinical sides of research. The AVRS will add to its membership representatives from the Nonhuman Primate (NHP) consortia, the Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), and the HIV Vaccine Trials Network (HVTN). 

Basic Sciences Program (Concept Review)

Overview of Women and HIV

Mary A. Young, M.D., Georgetown University

Dr. Young is an Assistant Professor of Medicine in the Division of Infectious Disease at Georgetown. She is a PI of the NIH-funded Women's Interagency HIV Study (WIHS), which is a longitudinal study of HIV-infected and non-infected women. Dr. Young presented a brief history of AIDS and an overview of HIV disease in women and the WIHS. The WIHS has contributed enormously to our understanding the dilemma of women living with AIDS, and provided information about the role of combination antiretroviral therapy (cART) and beliefs on sexual risk behaviors; alcohol, substance use, and the burden of mental health on treatment patterns; and gender-based violence on adherence.

WIHS 

Carolyn Williams, Ph.D., M.P.H., Chief, Epidemiology Branch, Basic Sciences Program, DAIDS 

The objective of WIHS-V is to continue support for the study and allow for expansion in areas of pathogenesis, virology, epidemiologic outcomes, and comparative effectiveness research in a representative cohort of U.S. women. This concept is a renewal, supported by the NIH Research Project (U01) grant mechanism. The award is for five years with planned funding for six to seven clinical sites, including one new clinical research site in the Southern U.S. and one data and analysis center. Additions to the concept are implementation science to the WIHS agenda along with an External Advisory Board to advise WIHS and DAIDS. Reviewers (Uittenbogaart and Celum) expressed enthusiastic support.

ARAC members emphasized the need for future research to focus more on various aspects of aging and co-morbidities, such as cardiovascular disease, osteoporosis and cancer. They also noted that the WIHS cohort can provide useful information about women at risk of HIV, which is extremely important as vaccine and other prevention trials have had difficulty enrolling this population. In addition, it was suggested that partner recruitment be considered with the new cohort. The addition of a site in the Southern U.S. was viewed as being very important, and offers the opportunity to include more women from rural areas in the cohort depending on the location of the future Southern site. The Committee supported the proposed approach of providing reduced funding to maintain the cohort and data at WIHS sites that do not successfully recompete. The scope of reduced awards would be limited to the cohort maintenance.

There was some discussion of the high retention of participants in the cohort and reasons for this success. Factors thought to contribute to the high retention include participant interest in the program, grantee staff engagement of participants, and participant perception of the value of the program, as well as modest reimbursement for transportation and other incentives.

The use of the repository, which is under a separate contract, was also discussed and staff noted that the samples in the repository are utilized at a relatively higher rate compared to other repositories by both internal and external investigators, and there are standard protocols in place to ensure high quality of the samples collected. The total cost of the program, including the cost of the repository, was noted by one Committee member, who suggested that the overall budget may need to be revisited in response to future budget challenges.

The ARAC members expressed support for the concept and voted approval without any modifications.

Vaccine Research Program (Concept Review)

HIV Vaccine Research and Design (HIVRAD)

Alan M. Schultz, Ph.D., Preclinical Research and Development Branch, NIAID, DAIDS 

The objective of the HIVRAD concept is to support multidisciplinary projects that address important scientific questions relevant to HIV vaccine discovery research. This concept is a renewal, supported by the NIH Program Project (P01) grant mechanism. The award is for five years with a first year cost of $5.0 million and number of awards ranging from one to three. HIVRAD was initiated in 1999 and has many past accomplishments. The program will continue to emphasize that research proposals must be “past the exploratory stage.” While the use of milestones were considered at one point, several members emphasized that they were not in favor of incorporating milestones into this program and prefer the emphasis to be on broad, basic science discovery and hypothesis generating studies. The reviewers (McCutchan and Birx) agreed on the value of the program, but expressed that the focus should be on getting the best submissions possibly and not on crafting milestones. 

The ARAC members expressed support for the concept and voted approval without any modifications.

Simian Vaccine Evaluation Units (SVEU) 

Nancy R. Miller, Ph.D., Preclinical Research and Development Branch, NIAID, DAIDS

The objective of the SVEU concept is to facilitate the identification of promising candidate AIDS vaccines by evaluating vaccine immunogenicity and efficacy in nonhuman primates. This concept is a renewal supported by the NIH (N01) Research and Development Contracts mechanism. The duration of the award is seven years with the number of awards ranging from two to three. The NHP Core Laboratories provide assay support for the SVEU vaccine studies but are supported under separate contracts (not included in this initiative). SVEUs were first awarded in 1991, and in the last ten years have conducted greater than 65 protocols investigating a wide variety of vaccines. Among other activities, the SVEU contracts prepare and conduct in vivo titrations of viral challenge stocks for SVEU studies and for the field. The reviewers (Picker and McCutchan) noted the important role SVEUs serve as a mechanism for vaccine access, resources, and evaluation. However, there were concerns about: 1) resources not being directly subject to peer review; 2) making it clear that SVEUs should not be the only way an efficacy study can be performed; 3) requesting assurance that the animals are screened for MHC and TRIM5 (variations in these host genetic factors may impact coreceptor usage and subsequently, viral replication). They also asked for clarification of the relationship between the proposed studies and the conduct of the studies under a SVEU.

In discussion it was noted that the unsolicited projects must find money in their grant awards to support primate studies. The availability of the SVEU contracts provides another option that investigators can use to do primate work that does not require funding from their individual research grant. The SVEU program receives more requests for primate studies than they can handle but applicants are taken in order of priority and most will get done. Within the preclinical branch of the DAIDS Vaccine Research Program, there is a defined process for identifying what studies and what samples are of highest priority. One committee member suggested in writing that the budget of the SVEUs be made smaller and be of shorter duration, but otherwise, all members voted to approve the concept without any modifications. Committee members also expressed the value of DAIDS providing standardized in vivo and in vitro virus stocks under a contract mechanism.

The ARAC members expressed support for the concept and voted approval without any modifications. 

Nonhuman Primate Core Laboratory: Functional Genomics 

Jonathan T. Warren, Ph.D., Preclinical Research and Development Branch, NIAID, DAIDS

The objective of this concept is to apply and refine high-throughput functional genomics approaches to evaluate vaccine-induced adaptive and innate immune responses and vaccine efficacy in NHP challenge/protection studies supported by DAIDS SVEU contracts and DAIDS grantees with the primary goal of identifying responses that predict vaccine efficacy. This concept is new, supported by the NIH (N01) Research and Development Contracts mechanism. The award is for five years and the number of awards is one. Functional genomics studies are proving valuable in vaccine research, and the services provided by this contract will directly support the activities of AIDS vaccine NHP protocols within the SVEU contracts and grant portfolio. The approach will include the generation of transcriptomic signatures, data analysis using bioinformatics, optimization of sampling methods, and the development of gene expression profiles to better predict vaccine efficacy. The reviewers (Lieberman and Picker) concur that the approach, which provides for quality control, assay development, and exploration of novel methods of data analysis, is excellent. They suggest that studies must be carefully selected, and data should be available online in real-time with a way to test alternative modes of analysis. The reviewers support the concept with the following caveats: 1) targeted transcriptional analyses to address specific issues, especially analyses of immune inductive sites and sites of virus transmission, and not for all vaccine studies within SVEUs; and 2) focus on specific cell subsets at well-defined tissue sites. Given the amount of funding available, only a limited number of studies can be conducted with a limited number of assay types, it was recommended that these be planned with care. It was also noted that it would be valuable to assure that this contract provide quality control, assay development, and exploration of novel methods of data analysis.

The ARAC members expressed support for the concept and voted approval without any modifications.

Prevention Sciences Program

Integrated Pre-clinical/Clinical Program for HIV Topical Microbicides (IPCP-HTM)

James A. Turpin, Ph.D., Microbicide Research Branch, Prevention Sciences Program, NIAID, DAIDS 

The objectives of the IPCP-HTM concept are to stimulate a strong, diverse base in preclinical discovery, develop new topical microbicides and combination strategies for vaginal, penile, and/or rectal use, and support translation from preclinical to pre-Phase 1 clinical studies. This concept is a renewal, supported by the U19, Research Program--Cooperative Agreements mechanism. The duration of the award is four years for preclinical and 5 years for clinical, with a first year cost of $7.7million; the number of awards ranges from one to three. The program is designed to evolve, addressing changes in microbicide and prevention science as preclinical and clinical proof-of-concepts are obtained. The reviewers (Carter, Celum, and Warren) agreed that the concept appears to be integrated and in balance with other NIAID prevention programs and will bring innovation in various areas to microbicide development.

In discussion, the importance of maintaining a balance between support and expansion of preclinical and early clinical research and the clinical activities of the Microbicide Trial Network was noted. The committee also discussed and supported the small but important addition of funds to develop biomedical mechanisms to measure adherence, which could provide critical feedback for refining product development. They asked for clarification about work in developing microbicides for other sexually transmitted diseases and collaborations with the Division of Microbiology and Infectious Diseases and one member thought it would be good have incentives available to strengthen these linkages. Overall, the Committee felt that this is a well developed and valuable program.

The ARAC members expressed support for the concept and voted approval without any modifications. 

VII. Adjournment

The meeting of the Council was adjourned at 3:59 p.m., on Monday, September 19, 2011.

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

 

-s-

Anthony S. Fauci, M.D.

Chair, National Advisory Allergy and Infectious Diseases Council

Director, National Institute of Allergy and Infectious Diseases

10/28/2011
Date
-s-

Marvin R. Kalt, Ph.D.

Executive Secretary

National Advisory Allergy and Infectious Diseases Council

Director, Division of Extramural Activities

National Institute of Allergy and Infectious Diseases

10/26/2011
Date

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

Last Updated August 20, 2013

Last Reviewed August 20, 2013