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Induction of Positive Cellular and Humoral Immune Responses by a Prime-Boost Vaccine Encoded with Simian Immunodeficiency Virus gag/pol¹

Kenji Someya^*, Yasushi Ami, Tadashi Nakasone^*, Yasuyuki Izumi^*, Kazuhiro Matsuo^*, Shigeo Horibata^*, Ke-Qin Xin, Hiroshi Yamamoto, Kenji Okuda, Naoki Yamamoto^* and Mitsuo Honda^2,*

^* AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan; Division of Experimental Animal Research, National Institute of Infectious Diseases, Tokyo, Japan; Department of Bacteriology, Yokohama City University, School of Medicine, Yokohama, Japan; and Laboratory Animal Research Center, Toyama Medical and Pharmaceutical University, Toyama, Japan

It is believed likely that immune responses are responsible for controlling viral load and infection. In this study, when macaques were primed with plasmid DNA encoding SIV gag and pol genes (SIVgag/pol DNA) and then boosted with replication-deficient vaccinia virus DIs recombinant expressing the same genes (rDIsSIVgag/pol), this prime-boost regimen generated higher levels of Gag-specific CD4⁺ and CD8⁺ T cell responses than did either SIVgag/pol DNA or rDIsSIVgag/pol alone. When the macaques were i.v. challenged with pathogenic simian/HIV, the prime-boost group maintained high CD4⁺ T cell counts and reduced plasma viral loads up to 30 wk after viral challenge, whereas the rDIsSIVgag/pol group showed only a partial attenuation of the viral infection, and the group immunized with SIVgag/pol DNA alone showed none at all. The protection levels were better correlated with the levels of virus-specific T cell responses than the levels of neutralization Ab responses. These results demonstrate that a vaccine regimen that primes with DNA and then boosts with a replication-defective vaccinia virus DIs generates anti-SIV immunity, suggesting that it will be a promising vaccine regimen for HIV-1 vaccine development.

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