6. Animal Models

Immunogenicity and toxicity assassment in animal models

Candidate vaccines were - independently from the employed delivery system - tested in BALB/c and C57BL/6 mouse models in order to determine the optimal antigen dose, route and timing of consecutive immunizations. These easy to approach animal models provided initial insight into the impact of adjuvant strategies and supported the direct in vivo comparison of various delivery systems. Furthermore, these analyses helped to figure out the most efficient prime boost regimens prior to proceeding to vaccination of non-human primates. Routine assessments comprised quantitative and qualitative analysis of humoral (IgM, IgG1, IgG2a, IgA via ELISA, Luminex) and cellular immune responses (╬│IFN, IL2, IL4, IL6, others depending on the objective of the study via ELISPOT, FACS).

So far, vaccine efficacy has been tested exclusively in collaboration with the primate centers in Germany (DPZ; Dr. Stahl-Hennig; Prof. Hunsmann) and Rijswijk (NL; Prof. Heeney). In most cases, rhesus macaques were injected either intravenously or via the rectal route (depending on the study objective, respectively) using the pathogenic SIV/HIV chimera SHIV89.6p for the challenge. In this model, several immunogen combinations protected monkeys from loss of CD4+ T cells, controlled the virus in some cases below detection levels and prevented clinical symptoms. Protection seemed to correllate with a balanced (Th1 + Th2) immune response that was directed towards multiple epitopes in more than 1 viral polypeptide.

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