Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV) in macaques vaccinated with replication-deficient viral vectors
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* Corresponding author: Barbara Falkensammer barbara.falkensammer@i-med.ac.at
1 Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, Fritz-Pregl-Str. 3, 6020 Innsbruck, Austria
2 Department of Infection Models, German Primate Centre, Kellnerweg 4, 37077 Göttingen, Germany
3 Department of Molecular and Medical Virology, Ruhr-University, Bochum, Universitätsstraße 150, 44801 Bochum, Germany
4 Robert Koch-Institut, Nordufer 20, 13353 Berlin, Germany
5 Department for Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Schöpfstr. 41/1, 6020 Innsbruck, Austria
6 Department of Pathology and Körber Laboratory for AIDS Research, Bernhard-Nocht-Institute for Tropical Medicine, Postfach 30 41 20, 20324 Hamburg, Germany
Retrovirology 2009, 6:60 doi:10.1186/1742-4690-6-60
Published: 21 June 2009Abstract
Background
We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV) encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens.
Results
Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p < 0.03) compared to controls. Considerable amounts of neutralizing antibodies were induced in systemic immunized monkeys. Most of the sera harvested during peak viremia exhibited a trend with an inverse correlation between complement C3-deposition on viral particles and plasma viral load within the different vaccination groups. In contrast, the amount of the observed complement-mediated lysis did not correlate with the reduction of SIV titres.
Conclusion
The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.