115 DNA and Protein Vaccination via Electroporation Confers Protection Upon Mucosal Challenge With Heterologous SIVsmE660.

Pavlakis, G.N.; Jalah, Rashmi; Patel, V.; Kulkarni, V.; Valentin, A.; Alicea, C.; Rosati, M.; von Gegerfelt, A.; Sardesai, N. Y.
JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/01.qai.0000413734.14610.32

We have previously shown that macaques vaccinated by DNA intramuscular electroporation with optimized plasmid DNAs expressing SIVmac239 antigens develop potent immune responses able to reduce viremia of the high dose SIVmac251 challenge. To further improve immune responses and protection, different protocols combining DNA with protein immunization (coimmunization, prime-boost) were tested.

Co-delivery of SIV DNA and protein increased the magnitude, longevity, and avidity of humoral responses and the ability to cross-neutralize heterologous Envs. SIV-specific cellular responses were readily measured in blood and mucosal sites after the first immunization and remained high during the entire follow-up. Vaccinated macaques resisted infection by SIVsmE660 compared to naive controls (P = 0.05; stratified for Trim5a genotype). Two of 8 DNA-protein coimmunized animals did not get infected after 14 exposures, while all controls were infected by 6 exposures. Vaccinees had significantly lower peak VL (1.7 log, P = 0.03). A majority (75%) of vaccinees suppressed virus replication rapidly to undetectable levels, maintaining normal CD4 counts (40 weeks of follow-up). Virus acquisition correlated with antibody avidity to SIVsmE660 at day of challenge; acquisition and control of viremia also correlated with the presence of vaccine-induced cellular immune responses (CD4+ Effector Memory T-cells and IFNgamma+ GranzymeB+ cytotoxic T-cells).The vaccine combining DNA and protein in a single administration is a novel concept to achieve rapid, high, persistent, broad and effective immune responses, and captures the best properties of both procedures: high and broad range of cellular immune responses produced by DNA and strong antibody responses.

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