MARBURG VIRUS-VACCINES BASED UPON ALPHAVIRUS REPLICONS PROTECT GUINEA-PIGS AND NONHUMAN-PRIMATES

Marburg virus (MBGV), for which no vaccines or treatments currently ex ist, causes an acute hemorrhagic fever with a high mortality rate in h umans. We previously showed that immunization with either killed MBGV or a glycoprotein (GP) subunit prevented lethal infection in guinea pi gs. In the studies reported here, an RNA replicon, based upon Venezuel an equine encephalitis (VEE) virus, was used as a vaccine vector; the VEE structural genes were replaced by genes for MBGV GP, nucleoprotein (NP), VP40, VP35, VP30, or VP24. Guinea pigs were vaccinated with rec ombinant VEE replicons (packaged into VEE-like particles), inoculated with MBGV, and evaluated for viremia and survival. Results indicated t hat either GP or NP were protective antigens while VP35 afforded incom plete protection. As a more definitive test of vaccine efficacy, nonhu man primates (cynomolgus macaques) were inoculated with VEE replicons expressing MBGV GP and/or NP. Three monkeys received packaged control replicons (influenza HA); these died 9 or 10 days after challenge, wit h typical MBGV disease. MBGV NP afforded incomplete protection, suffic ient to prevent death but not disease in two of three macaques. Three monkeys Vaccinated with replicons which expressed MBGV GP, and three o thers vaccinated with both replicons that expressed GP or NP, remained aviremic and were completely protected from disease.