Adjuvant-dependent cytokine profiles in the context of a DNA prime-protein boost HIV vaccine (113.23)

Abstract

Abstract Heterologous prime-boost vaccination approaches have emerged as a promising strategy to generate protective immunity against a variety of pathogens in animal and human studies. Our previous studies demonstrated that HIV-1 gp120 DNA vaccine prime-protein boost elicits improved neutralizing antibody responses. To understand the mechanisms that regulate the immune responses in prime-boost vaccination strategy, current studies were designed to define the cytokine profiles associated with different adjuvants used in such regimens. A polyvalent vaccine DP6-001, including gp120 antigens from 5 different primary viral isolates, was used as the model vaccine. Any influence of endotoxin associated with DNA plasmid preparation was first excluded, as regular DNA preparations did not elicit different immune response when tested in vivo against endotoxin-free DNA preparations. Next we studied the effects of several adjuvants, QS-21, alum, and MPL, on the immunogenicity of DP6-001 in a mouse model. gp120-specific antibody and T cell responses, and innate cytokine production, were monitored at time points after immunizations and at termination. Our results indicate that different adjuvants may generate unique cytokine profiles and improve the immunogenicity of DP6-001. This study may provide valuable information in selection of an adjuvant for inclusion in future prime-boost vaccination strategies, with the goal of enhancing immunogenicity while minimizing reactogenicity.