Reduction of simian-human immunodeficiency virus 89.6P viremia in rhesus monkeys by recombinant modified vaccinia virus Ankara vaccination

Since cytotoxic T lymphocytes (CTLs) are critical for controlling human imm unodeficiency virus type 1 (HIV-1) replication in infected individuals, can didate HIV-1 vaccines should elicit virus-specific CTL responses. In this r eport, we study the immune responses elicited in rhesus monkeys by a recomb inant poxvirus vaccine and the degree of protection afforded against a path ogenic simian-human immunodeficiency virus SHIV-89.6P challenge. Immunizati on with recombinant modified vaccinia virus Ankara (MVA) vectors expressing SIVmac239 gag-pol and HIV-1 89.6 env elicited potent Gag-specific CTL resp onses but no detectable SHIV-specific neutralizing antibody (NAb) responses . Following intravenous SHIV-89.6P challenge, sham-vaccinated monkeys devel oped low-frequency CTL responses, low-titer NAb responses, rapid loss of CD 4(+) T lymphocytes, high-setpoint viral RNA levels, and significant clinica l disease progression and death in half of the animals by day 168 postchall enge. In contrast, the recombinant MVA-vaccinated monkeys demonstrated high -frequency secondary CTL responses, high-titer secondary SHIV-89.6-specific NAb responses, rapid emergence of SHIV-89.6P-specific NAb responses, parti al preservation of CD4(+) T lymphocytes, reduced setpoint viral RNA levels, and no evidence of clinical disease or mortality by day 168 postchallenge. There was a statistically significant correlation between levels of vaccin e-elicited CTL responses prior to challenge and the control of viremia foll owing challenge. These results demonstrate that immune responses elicited b y live recombinant vectors, although unable to provide sterilizing immunity , can control viremia and prevent disease progression following a highly pa thogenic AIDS virus challenge.