ALLOMICROVAC - A combined microbicidal-immunizing strategy against SIV and HIV infection (Life sciences, genomics and biotechnology for health) (2007-01-01 - 2008-12-31) (»add to infobox)

The objective of the proposed project is to establish proof of concept that a tri-molecular construct, consisting of MHC antigens combined with microbial HSP70 and extracellular CCR5 can be utilized in microbicidal, preventive and therapeutic immunisation. This strategy utilizes a novel microbicidal construct to protect against mucosal SHIV infection in female macaques. However, as the construct is immunogenic, repeated applications will elicit mucosal, regional and systemic immunity. The preventive strategy is based on two 'experiments of nature', alloimmunity and homozygous 32 CCR5 mutation. The microbicidal-immunogenic agent elicits innate antiviral responses and targets different stages in the infectious process. Investigation of the three preventive modalities are outlined below. 1.  To select 3 common macaque MHC molecules (Mamu A1,A4,A8), expressed as novel Dextramer constructs, to inhibit mucosal transmission of SHIV. 2.  To combine the alloantigens with microbial HSP70 (70kD heat shock protein) and 3 extracellular peptides of CCR5 which inhibit transmission of R5 strains of SIV or HIV. 3.  To challenge macaques with SHIV SF162P (R5 strain of HIVenv gene construct), after each of 4 applications of the microbicidal agent and test for infectivity. 4.  To study vaginal antibodies, CC chemokine responses, and systemic innate and adaptive immune responses to the microbicidal agent and the challenge virus. 5.  To evaluate the microbicidal agent as a protective vaccine by challenging with SHIV SF162P those macaques not infected 2 months after the last application of the microbicide. 6.  To utilize the macaques that were infected for therapeutic immunization 2 months after infection by treating them with ART and immunizing them IM with the microbicidal construct. The strategy of combining a short term microbicide with a long-term preventive vaccine may deal with the serious difficulty of compliance, demanded by repeated application of microbicides before each intercourse.

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