Abstract
BackgroundWe 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.ResultsIndependent 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.ConclusionThe 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.
Highlights
We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV) encoding simian immunodeficiency virus (SIV) antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies
Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p < 0.03) compared to controls
The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge
Summary
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. Already during early stages of viral infection, antienvelope (env) antibodies (Abs) are thought to reduce viremia [1,2,3] Their effector functions are still not completely defined. Some of such neutralizing antibodies (nAbs) may inhibit viral entry either by interfering with structures of the gp120/gp complex [4] or with envepitopes that bind to chemokine receptors. They may cross-link virus particles and induce clearance of immune-complexed viruses by phagocytosis. ADCC has been studied in the SIV monkey model, was associated with the control of HIV in infected humans [68] and may contribute to a slower disease progression in long-term non-progressors [9]
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