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CENTRALIZED FACILITIES -AIDS VACCINE AND DRUG TESTING CHIMPANZEE RESOURCES

Objective

1 To perform efficacy testing of HIV-1 vaccines for prevention of HIV-1 infection. The ultimate goal of this Centralised Facility is to assist European Researchers to accelerate the development and evaluation of effective vaccines for AIDS. The criteria include a vaccine capable of providing long lasting and enduring immunity with heterologous cross protection from virus and infected cells across mucosal barriers.
2 To elucidate mechanisms or correlates of protective immunity to HIV-1 infection or disease and to define prognostic parameters of protection for assessment of clinical trials.
3 To investigate and compare the pathogenesis of HIV-1 infection in man vs chimpanzees: towards identifying new therapeutic strategies for the treatment of AIDS.
The European Centralized Chimpanzee Facility (ECCF) is a genetically defined outbred breeding colony of 120 chimpanzees. Preclinical research facilities for applications such as acquired immune deficiency syndrome (AIDS) research, gene therapy, hepatitis, malaria, bone marrow transplantation and immunotherapy research are available for testing European initiatives for effective new AIDS vaccines and therapeutics. A large rhesus monkey colony is used for refinement of studies if required before actual studies are carried out in chimpanzees. New biohazard housing facilities have been completed to provide a state of the art environment for these studies and encompasses the necessary clinical veterinary, haematology, serological, molecular biological virological laboratories for human immunodeficiency virus (HIV) research. These laboratories are currently engaged in several HIV-1 vaccine studies, vaccine development studies in the simian immunodeficiency virus (SIV)model and comparative pathogenesis projects oriented towards new therapeutic strategies for AIDS. The next steps in HIV-1 vaccine trials will involve using HIV-1 strains more relevant to the European population, for homologous as well as heterologous challenge experiments and cell associated and mucosal vaccine efficacy trials.

Remarkable similarities exist between the MHC genes and CD4 between chimpanzees and man, but less so in rhesus macaques. Current evidence suggests an important role of CTLs in the elimination of virus infected cells. Evidence suggests that chimpanzees are able to contain HIV-1 infection and that this may be due to their ability to maintain APC integrity and TH1 function. We are currently investigating how virus load in chimpanzees compares to HIV infected patients and SIV infected macaques. In nature, SIVcpz infection of chimpanzees occurs only with thrombocytopenia, and marked NK cell fluctuations, but appparently without other immunological dysfunctions.
The development of a safe effective vaccine or vaccines for the prevention of human immunodeficiency virus (HIV) infection is of international importance to halt or slow the current pandemic of AIDS. The principle cause of AIDS is HIV-1, a retrovirus with an enormous potential for variability both within the human host and within the population. In order to appropriately design, test and evaluate vaccines intended to protect humans from infection with this virus, an animal model must be available which responds to HIV-1 infection similar to man. Until recently HIV-1 had been proven only to infect man and his great ape relatives, while seemingly only able to cause AIDS in man. Of the great apes, only captive bred chimpanzees (man's closet relative) have been found to be practical models for HIV-1 vaccine research. The unique envelope (env) characteristics of HIV-1 necessitates the use of the chimpanzee model for final testing of HIV-1 vaccine efficacy. HIV-1 differs importantly from HIV-2 and the Simian Immunodeficiency Virus (SIV) in terms of envelope conformation and neutralization epitopes, proven to be important in protective immunity. Other common laboratory primates such as rhesus macaques are unfortunately only suitable for SIV/HIV-2 studies. Captive breeding facilities for chimpanzees with housing for HIV-1 infected chimpanzees are an uncommon an invaluable resource in this regard. The search for other primate models of HIV-1 infection is ongoing and studies are planned to explore the possibility that Macaque species are also a suitable model for HIV-1 infection. The ECCF provides a European Centralized Facility for true centralized and standardized efficacy testing of HIV-1 vaccines utilizing the chimpanzee model as the critical test and for establishing clinical trials guidelines, while HIV-1 efficacy studies of a more preliminary nature are proposed to be first carried out using available SIV and SHIV models in macaques.

Funding Scheme

CON - Coordination of research actions

Coordinator

Biomedical Primate Research Centre TNO
Address

2280 HV Rijswijk
Netherlands