E112 Comparison of systemic and mucosal responses after DNA and protein co-immunization.

Pavlakis, George N.; Jalah, Rashmi; Valentin, Antonio; Rosati, Margherita; Patel, Vainav; Kulkarni, Viraj; Alicea, Candido; Kelly, Rachel Beach; Guan, Yongjun; Lifson, Jeffrey D.; Hirsch, Vanessa M.; Venzon, David; Broderick, Kate E.; Sardesai, Niranjan Y.; LaBranche, Celia; Montefiori, David C.; Shen, Shaunna; Tomaras, Georgia; Felber, Barbara K.
JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/01.qai.0000429250.47405.22
Abstracts: PDF Only

Optimal protocols of DNA only vaccination elicit robust and broad humoral and cellular responses. These immune responses are able to significantly reduce peak and chronic viremia in macaques challenged with high dose SIVmac251. Despite the strong humoral responses, protein boost after DNA vaccination greatly increased Ab levels. Importantly, a co-immunization strategy of DNA&protein injected in the same muscle the same time induced highest and broadest humoral responses. Similar data were obtained using purified Env protein instead or viral particles. Inclusion of DNA in the vaccine promoted persistence of plasma antibody levels over long time (>2 yrs). DNA/protein vaccination induced: higher SIV Env-specific IgG in saliva; more responders with higher SIV Env-specific IgG in rectal fluids; higher and longer-lasting plasma bAb and Nab to homologous and heterologous Env. Vaccine-induced Ab responses against SIVsmE660 correlated with slower virus acquisition. Two of DNA&protein coimmunized macaques with high and persistent Ab responses showed sterilizing immunity after 14 exposures, while all controls were infected by 6 exposures. DNA&protein co-delivery increases the magnitude, quality and longevity of systemic and mucosal humoral immune responses in immunized rhesus macaques.

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