May 2004

Resources for HIV Vaccine Research and Development

1. Fundamental Research Supported Through RO1s

   1. NIAID has an extensive portfolio of grants directed at understanding
      • Mechanism of virus binding and entry
      • Methods of virus spread during the establishment of infection
      • Studies of establishment and spread of infection
      • Structure, function studies of HIV proteins
      • Basic immunology
      • HIV antigenic and nucleic acid variation

2. Vaccine Discovery, Screening, and Preclinical Research

   1. Innovation Grant Program (IGP): IGP fosters exploratory investigator-initiated AIDS vaccine research at the earliest stages of concept genesis and evaluation. As such, a premium is placed on high-risk, high-impact studies and those believed to have a high likelihood of advancing the field.

   2. HIV Research and Design (HIVRAD): HIVRAD supports basic vaccine research and design, including concept testing in animal models, development of potential vaccine candidates and evaluation of their mechanism of action, studies of immune correlates, and animal model development. Its goal is to advance the development of vaccine concepts identified in Innovation Grant studies or in other early preclinical research.

   3. Integrated Preclinical/Clinical AIDS Vaccine Development Program (IPCAVD): The IPCAVD program targets research at the preclinical-clinical interface of the HIV vaccine research and development pipeline. The program supports consortia of experts in animal models, molecular biology, immunology, and early clinical trials to pursue the iterative process of vaccine development, evaluation, and refinement of specific vaccine concepts. Vaccine clinical lot production and early human clinical studies within the period of the award are expected.

   4. HIV Vaccine Design and Development Teams (HVDDT): HVDDT consists of consortia of scientists from industry and/or academia who have identified specific promising vaccine concepts amenable to targeted, accelerated product development. They are milestone-driven contracts designed to encourage rapid advancement of important products into clinical studies in a timely manner within the five year period of the award.

   5. Vaccine Development Resources Contracts: A group of HIV-1 vaccine development resources contracts that promote the preclinical development of promising vaccine candidates. Resources are available to accomplish several basic functions.
      • Manufacture of GMP pilot lots of vaccine for testing in humans
      • Manufacture of GLP/reagent grade vaccines and clinical grade vaccines for testing in non-human primates
      • Preclinical testing of GMP produced vaccine candidates (e.g., safety, immunogenicity)
      • Preparation of Food and Drug Administration submissions leading up to human trials (e.g., Investigational New Drug (IND) submissions to FDA)
      • For vaccine manufacturing, resources are currently available to produce reagents (GLP) or trial (GMP) vaccines within the following categories
        • Recombinant protein subunits
        • DNA plasmids and/or DNA vaccines
        • Viral vector-based vaccines
        • Whole killed virus

   6. Master Contract for HIV Vaccine Production and Development: to speed up the process of initiating new vaccine production projects and to expand current capabilities under the Vaccine Development Resources Contract, a Master Contractor for HIV Vaccine Production and Development will be competitively awarded in 2004. This contract mechanism will support the production of vaccines and microbicides, the execution of preclinical safety and immunogenicity testing and collection, and the submission of documentation to the FDA for Investigational New Drug (IND) approval.

   7. Animal Models: Simian Vaccine Evaluation Units (SVEUs) and associated core laboratories evaluate promising SIV and HIV vaccines in non-human primates in order to accelerate HIV vaccine development. The following non-human primates are available for in vivo studies: Indian rhesus macaques, Chinese rhesus macaques, pigtailed macaques, and cynomologous macaques. The sites and laboratories include:
      • Advanced BioScience Laboratories
      • Southern Research Institute
      • University of Washington
      • Beth Israel Hospital
      • Duke University

3. Clinical Research

   1. HIV Vaccine Trials Network (HVTN): NIAID-supported clinical trials of preventive HIV vaccines are centered in the HVTN. The HVTN, a global research network with 14 international and 20 domestic sites, has a comprehensive program of research to identify an effective and safe vaccine to prevent HIV/AIDS by studying the safety, immunogenicity, and efficacy of candidate HIV vaccines. Directly and through collaborations with other investigators, the HVTN also supports fundamental research relevant to HIV vaccine development and pathogenesis, including clinical evaluation of the relevance of global viral and host genetic variation in vaccine immunogenicity, to better understand the fundamental scientific principles of HIV vaccine development.

   2. HLA Typing and Epitope Mapping: NIAID currently supports two contracts for HLA Typing and Epitope Mapping to Guide HIV Vaccine Research. The overall goals of these contracts are to identify the viral targets of the cellular T-cell responses and to characterize neutralizing antibody responses in the context of extensive viral sequence variability and diverse genetic polymorphisms. This information will facilitate the design and testing of candidate vaccines.

   3. HIV Prevention Trials Network (HPTN): The HPTN has the capacity to conduct multidisciplinary Phase I, II, and III trials of biomedical and behavioral interventions to prevent HIV transmission. The network includes 15 domestic and 14 international sites, and will focus on studies involving microbicides, sexually transmitted diseases, mother to infant transmission, antiretroviral therapy for prevention, behavioral interventions and control of injection drug use.

4. Training

   1. The NIH Loan Repayment Program (LRP), mandated by Congress in 1988, encourages health professionals to engage in AIDS-related research at NIH. Since the program enrolled the first participants in 1989, 232 professionals have been attracted to NIH as a result of loan repayment benefits, with more than half remaining longer than their contractually obligated period.

   2. For the past 10 years, the Fogarty International Center has supported the AIDS International Training and Research Program (AITRP), a multidisciplinary program designed to strengthen research capacity in the epidemiology, prevention, diagnosis, and treatment of HIV/AIDS in developing countries; to facilitate the evaluation of AIDS drugs and vaccines internationally; and to provide global scientific leadership in HIV/AIDS. The AITRP is active in 100 developing countries, with activities focused in the dozen countries that have the most serious current or emerging HIV/AIDS epidemics.

   3. The Fogarty International Center (FIC) has enhanced its HIV-AIDS and Related Illnesses Research Collaboration Award (AIDS-FIRCA), which provides support for collaboration between U.S. and foreign scientists in the foreign collaborator's laboratory through grants to U.S. investigators already conducting HIV-related research.

   4. The HVTN also has positions available to train scientists in developing countries.

5. Other Research Resources Available for the Global Research Community

   1. Reagent Resource Support for AIDS Vaccine Development provides reagents, resources, and quality assurance/quality control analysis (QA/QC) in support of the DAIDS vaccine research effort including the procurement or production and distribution of working quantities of common reagents needed for immunological evaluation of the vaccinated subjects participating in DAIDS-supported clinical and preclinical trials.

   2. NIH AIDS Research and Reference Reagent Program. Since 1988, the AIDS Research and Reference Reagent Program has served the worldwide research community by providing state-of-the-art biological and chemical materials for study of HIV and related opportunistic infections. More than 5,200 reagents are available to registered users.

   3. The Tetramer Facility was established in 1999 as a component of the NIH AIDS Research and Reference Reagent Program. It functions to provide custom synthesis and distribution of soluble major histocompatibility complex (MHC) I/peptide tetramer reagents that can be used to stain antigen-specific CD8 T cells. Some pre-assembled MHC Class II tetramers reagents are now available in limited trial lots. Tetramer reagents are synthesized at the NIAID Tetramer Facility contract site located at Emory University.

   4. HIV Database and Analysis Unit. This unit, based at the Los Alamos National Laboratory in New Mexico, consists of two related databases, the HIV Molecular Immunology Database and the HIV Genetic Sequence Database.

      • The HIV Molecular Immunology Database provides a comprehensive and searchable listing of defined HIV cytotoxic and helper T-cell epitopes and antibody binding sites epitopes. It includes epitope alignments, maps, and reference information for the cytotoxic and helper T-cell epitopes, and antibody-binding sites in HIV-1 immunologically reactive sites along with reviews pertaining to HIV immunology.

      • The Genetic Sequence Database compiles genetic information on HIV from GenBank and other international genetic databases, and then carries out in-depth analysis of this information.

   5. Genetic Sequence Variability of HIV-1 and Related Lentiviruses. This contract, currently held by the University of Alabama at Birmingham, carries out genetic cloning and sequencing studies. Through this contract, full-length proviruses representing clades A through H (group M subtypes), a number of subtype recombinant viruses, and several group O viruses, have been cloned and sequenced in their entirety. Individual viral genes have been subcloned into expression vectors as research tools. These clones can be used to produce proteins in various expression systems, for the creation of SIV-HIV chimeric viruses (SHIV), or directly in the design of vaccines. In addition, gag, pol, env, and nef genes from clades A through H have been subcloned into shuttle vectors for generating recombinant vaccinia viruses (also for use as research tools or vaccines).

   6. UNAIDS, formally known as the UNAIDS Network for HIV Isolation and Characterization, sponsors an international collaboration among more than a dozen laboratories. UNAIDS obtains patient materials from HIV-infected individuals at sites around the world and then distributes these materials to network laboratories for virological and immunological studies. NIAID provides for large-scale expansion, storage, immunological and biological characterization of virus isolates, and transfer of these isolates to vaccine companies and other UNAIDS collaborating laboratories. In addition, the NIAID-supported HIV Database and Analysis Unit serves as the database for this activity. To date, close to 200 viruses have been isolated through this project.

6. Other

   Dale and Betty Bumpers Vaccine Research Center: The Vaccine Research Center (VRC) is an intramural research division within NIAID dedicated to developing an AIDS vaccine. This multidisciplinary effort brings together basic scientists, clinical investigators, and translational researchers to accelerate the generation of a vaccine for this deadly disease. Housed in a new research building that began operations in August 2000, the center has assembled a team of world-class structural biologists, virologists, immunologists, clinical trial physicians and nurses, and vaccine production engineers.

   The VRC team is dedicated to translating the latest concepts in the HIV disease process and in immunology into new strategies for AIDS vaccines. At full capacity, the VRC will employ about 125 scientists and support staff led by its Director, Gary J. Nabel, M.D., Ph.D. In addition to the VRC scientific programs, the facility contains core laboratories in immunology, flow cytometry, vector development, vaccine production, a biocontainment laboratory, an animal facility, and a clinical trials program.

   The VRC hopes to advance the science of vaccine development by incorporating basic and applied research with clinical trials methods in a single center with the capacity for vaccine production. The center will actively collaborate with NIH intramural and extramural scientists to facilitate the movement of ideas from the broader community into clinical trials. The VRC maintains close ties with extramural investigators in the HVTN, where the infrastructure for conducting larger scale trials is already established, to characterize safety and immunogenicity of promising vaccine approaches.

   This collaboration will include efforts to develop vaccine candidates that can be evaluated at international field sites. When products emerge with promise for licensure, the VRC will also engage the pharmaceutical industry's large capacity for, and experience in, product development and distribution.

NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.

News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

Prepared by:
Office of Communications and Public Liaison
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD 20892

U.S. Department of Health and Human Services

Department of Health and Human Services

National Institutes of Health (NIH) Bethesda, Maryland 20892

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