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AIDS research in macaques

Objective

To foster the development of a relevant animal model for human AIDS to study immunodeficiency virus pathogenesis, to evaluate the possibility of vaccines that will prevent the transmission of such viruses or protect against their pathogenic potential and to design and test therapeutic interventions, in particular immune-based strategies.
The concerted action (CA) was established to foster the development of a relevant animal model for human acquired immune deficiency syndrome AIDS to study immunodeficiency virus pathogenesis, to evaluate the possibility of vaccines that will prevent the transmission of such viruses or protect against their pathogenic potential and to design and test therapeutic interventions and in particular immune based strategies.

The simian immunodeficiency virus (SIV) strain SIVmac251/32 H was selected as the basis of a cooperative vaccine trial. This trial was conducted among 10 participating primate facilities in 6 European countries. Over 100 animals both rhesus and cynomolgus macaques were immunized or served as controls. Immunization began in 1990 with 3 types of antigen formulation and 4 adjuvant compositions. The experiment continued during 1991.
The results of the first cooperative vaccine trial were as follows:
more than 60 animals were protected against challenge with both homologous and heterologous simian immunodeficiency viruses;
partial protection was also achieved against infection with virus producing cells;
inactivated and split virus vaccines both protected monkeys against SIV infection;
the optimum antigen dose was found to be between 1 mg and 2 mg of viral material. 3 immunizations were as effective as 4;
the results obtained with rhesus or cynomolgous monkeys were comparable;
animals were protected for at least several months up to half a year after the last immunization;
the duration of protection depended on the type of adjuvant.

At that time this trial was certainly the most comprehensive and best designed experiment to evaluate the possibility of an AIDS vaccine.
Relevant animal models have been the pivotal technique in clinical microbiology to study pathogenesis and to develop effective measures such as vaccines and antimicrobial drugs to combat infections. Thus, an animal model relevant to human AIDS was urgently required. In 1987 it became apparent that such a model could be developed by infecting macaques with various simian (SIV) or human immunodeficiency viruses (HIV). Therefore, the Commission of the EC initiated a Concerted Action aimed to establish such a model. The founding meeting was attended by scientists from Deutsches Primatenzentrum (DPZ), Goettingen, TNO Primate Centre, Rijkswijk, Centre de Recherches du Service de Sante des Armees, Commissariat de l'Energie Atomique (CRSSA), Fontenay-aux-Roses near Paris, and the National Institute for Biological Standards and Control (NIBSC), Potters Bar near London. A concerted Action (CA) as well as a related Centralized Facility (CF) were set up. The DPZ was commissioned with the coordination and administration.

The programme started in 1988 and gradually the Concerted Action was joined by scientists from the Centre of Applied Microbiology and Research (CAMR), Salisbury, the Paul-Ehrlich-Institut (PEI) in Langen near Frankfurt, the Gesellschaft fuer Straheln- und Umweltforschung (GSF), Neuherberg near Munich, the National Bacteriological Laboratory (NBL), Stockholm, and the Istituto Superiore di Sanita (ISS), Rome.

The mission of the CA and CF was to:
- establish a relevant animal model for AIDS research by infection of macaque monkeys with HIV- and SIV-isolates;
- select a particular animal virus system and to jointly perform experiments into the pathogenesis of primate immunodeficiency viruses, vaccine development and possibilities of treatment;
- to set common standards in the envisioned animal experiments, in order to facilitate direct comparison of data obtained in individual European laboratories;
- to allow the confidential exchange of information on ongoing experiments in the participating centres sponsored by national resources to avoid unnecessary duplication.

Funding Scheme

CON - Coordination of research actions

Coordinator

DEUTSCHES PRIMATENZENTRUM GMBH
Address
Kellnerweg 4
37077 Goettingen
Germany