In the present study, the immunogenicity and protective efficacy of a recombinant vaccinia virusbased simian immunodeficiency virus (SIV) vaccine, given alone or in combination with a protein boost, were investigated. Cynomolgus macaques were immunized intramuscularly with modified vaccinia virus Ankara (MVA) expressing the SIVsm env and gag-pol genes (MVA-SIVsm) at 0 and 3 months (n l 4), at 0, 3 and 8 months (n l 4) or at 0 and 3 months followed by purified native SIVsm gp148 and recombinant

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... IVmac p27 in immunostimulatory complexes at 8 months (n l 4). One month after the last immunization, the vaccinees, together with four naive control monkeys and four monkeys immunized with wild-type MVA, were challenged intrarectally with 10 MID 50 SIVsm. At the time of challenge, antibody titres to SIV Env and lymphocyte proliferation responses to whole viral antigen were highest in vaccinees receiving MVA-SIVsm in combination with protein immunizations. Following rectal challenge, one of these vaccinees was completely protected. A prolonged survival time was observed in two of four monkeys in each of the groups immunized with MVA-SIVsm, in two monkeys given MVA-SIVsm followed by protein and in three of four monkeys given wild-type MVA, compared with naive controls. In conclusion, one monkey given the combined vaccine was protected completely against SIVsm infection. Furthermore, immunization with MVA-SIVsm, as well as wild-type MVA alone, seemed to delay disease progression after mucosal SIV infection in a proportion of the monkeys. S.-L. (1999a). Protection of macaques against intrarectal infection by a combination immunization regimen with recombinant simian immunodeficiency virus SIVmne gp160 vaccines. Journal of Virology 73, 3134-3146. S.-L. (1999b). Role of immune responses against the envelope and the core antigens of simian immunodeficiency virus SIVmne in protection against homologous cloned and uncloned virus challenge in macaques. Journal of Virology 73, 8201-8215.