Immunization against SIVmne in macaques using multigenic DNA vaccines

All structural and regulatory genes of SIVmne were cloned into mammalian ex pression vectors to optimize expression in vitro and immunogenicity in mice . Macaca fascicularis were immunized four times with plasmid DNA (n = 4), o r two DNA priming inoculations followed by two boosts of recombinant gp160 plus Gag-Pol particles (n = 4). Following intrarectal challenge with SIVmne , all macaques be came infected. Three monkeys immunized with DNA alone mai ntained low plasma virus loads by 1 year post-challenge; the fourth exhibit ed high virus loads and significant CD4(+) cell decline. Two of the DNA plu s boost and three control macaques had high virus loads and associated CD4( +) cell decline. Both vaccine protocols elicited antibodies and comparable helper T-cell proliferative responses to gp160. Cytokine mRNA levels in act ivated peripheral blood mononuclear cells (PBMC) takes at time of challenge suggested a dominant T helper (Th) 1 state in three DNA-immunized and one protein-boosted macaque, which correlated with low virus loads and high CD4 (+) cell counts post-challenge.