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HIV/AIDS News

Resources for HIV Vaccine Research and Development

Date: May 1, 2002
Source: National Institutes of Health (NIH)
Author: National Institute of Allergy and Infectious Diseases (NIAID)

The discovery and development of safe, efficacious, cost-effective vaccines to prevent HIV infection and/or disease worldwide are among the highest priorities of the National Institutes of Health (NIH) AIDS research program. Within NIH, the National Institute of Allergy and Infectious Diseases (NIAID) has the primary responsibility for HIV vaccine research and development.
A. Fundamental Research Supported Through RO1s
1. NIAID has an extensive portfolio of grants directed at understanding
a. Mechanism of virus binding and entry
b. Methods of virus spread during the establishment of infection
c. Studies of establishment and spread of infection
d. Structure, function studies of HIV proteins
e. Basic immunology
f. HIV antigenic and nucleic acid variation
2. The Mechanisms of AIDS Pathogenesis Program solicits hypothesis-driven in vivo HIV and AIDS pathogenesis research by collaborative multidisciplinary research teams. For HIV vaccine studies, this program seeks applications that address
a. Mechanisms of establishment of viral infection, including mucosal transmission
b. Immunological and virological events controlling primary infection
c. Host and virological factors modulating latent cellular and tissue reservoirs of HIV, including compartmentalization of virus
d. Host factors that modulate viral infection and/or disease progression
e. Host and viral factors regulating interspecies transmission of HIV/SIV
f. Mechanisms of protection induced by attenuated viruses
g. Impact of vaccination on viral transmission and/or disease progression
h. Transgenic animal models for HIV infection
The most relevant studies are expected to examine molecular and cellular biology, virology, and immunology within the context of animal models and/or well-defined human cohorts or patient samples. NIAID also encourages studies examining HIV transmission and pathogenesis in the context of the gastrointestinal mucosal tissues.
B. 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. Early human 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 to encourage rapid advancement into clinical studies.
5. Vaccine Production Resources: A group of HIV-1 vaccine development resources contracts aids 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 vaccine for testing in non-human primates
· Preclinical testing of GMP produced candidates (e.g., safety, immunogenicity)
· Preparation of Food and Drug Administration submissions leading up to human trials
For vaccine manufacturing, resources are currently available to produce reagents (GLP) or trial (GMP) vaccines within the following categories
· Recombinant protein subunits
· DNA vaccines
· Viral vector-based vaccines
6. Animal Models: Simian Vaccine Evaluation Units (SIVEUs) and 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
7. New Technologies for HIV and HIV Vaccine Research: This grant program supports the use of novel and innovative technologies to: 1) detect HIV, 2) quantitate and optimize measurement of immune responses to HIV and to candidate HIV vaccines, and 3) evaluate and quantitate immune responses responsible for the efficacy of licensed vaccines for other infectious diseases. The objectives are to assist with the development of sensitive, standardized assays for use in clinical HIV vaccine studies and to obtain a clearer understanding of the correlates of protection from HIV infection and immune-mediated control of disease progression so as to facilitate vaccine design.
C. 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 11 international and 18 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. 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.
D. Training
· 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, 115 professionals have been attracted to NIH as a result of loan repayment benefits, with more than half remaining longer than their contractually obligated period.
· 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.
· The Fogarty International Research Collaboration Award for AIDS 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.
· The HVTN also has positions available to train scientists in developing countries.
E. Other Research Resources Available for the Global Research Community
1. 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 1,670 reagents are available to registered users.
2. Tetramer Facility. Currently a component of the NIH AIDS Research and Reference Reagent Program, the Tetramer Facility provides 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. In the future, MHC II/peptide reagents should become available for the staining of antigen-specific CD4 T cells. Tetramer reagents will be synthesized at the NIAID Tetramer Facility contract site located at Emory University.
3. 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 listing of defined HIV 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.
4. 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.
5. Collaboration with 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.
F. 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 (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
Press 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