Abstract
Methods We evaluated immunogenicity of DNA and protein vaccines encoding SIVmac251 and SIVsmE660 gp145 in rabbits and rhesus macaques. DNA vaccines encoding wild type gp145 or mutated gp160 truncated at Q708 were used. Trimeric wildtype gp145 proteins, stably expressed and purified from 293T cells, were used with Advax delta inulin adjuvant to boost after DNA immunization. Macaques were electroporated with wild type DNA of both isolates followed by adjuvanted homologous protein boosts. Rabbits received DNA vaccine alone, delivered by electroporation. Neutralization assays were performed in TZM-bl cells with SIVmac251 and SIVsmE660 isolates that are partially resistant to neutralization.
Highlights
Partial success of the human RV144 clinical trial underscored the importance of envelope antibody responses for an effective HIV-1 vaccine
Characterization in rabbits & nonhuman primates of the neutralizing antibody response elicited by DNA & protein vaccination with SIVmac251 & SIVsmE660
We evaluated immunogenicity of DNA and protein vaccines encoding SIVmac251 and SIVsmE660 gp145 in rabbits and rhesus macaques
Summary
Partial success of the human RV144 clinical trial underscored the importance of envelope antibody responses for an effective HIV-1 vaccine. Immunogenicity studies with SIV envelope proteins typically neutralize TCLA isolates. Folded trimeric envelope proteins delivered with appropriate adjuvants may successfully elicit antibodies with broad neutralization specificity
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