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        Safety, immunogenicity, and protective efficacy of NYVAC-JEV and 
        ALVAC-JEV recombinant Japanese encephalitis vaccines in rhesus monkeys.

           Raengsakulrach B, Nisalak A, Gettayacamin M, Thirawuth V, Young GD,
           Myint KS, Ferguson LM, Hoke CH Jr, Innis BL, Vaughn DW
           Department of Virology, Armed Forces Research Institute of Medical
           Sciences, Bangkok, Thailand.
           Am J Trop Med Hyg 1999 Mar;60(3):343-9

        Two poxvirus-vectored vaccines for Japanese encephalitis (JE), NYVAC-JEV
        and ALVAC-JEV, were evaluated in rhesus monkeys for safety,
        immunogenicity, and protective efficacy. The vaccines were given to four
        monkeys each on study days 0 and 28 along with saline placebo on day 7.
        For controls, the licensed BIKEN JE vaccine and a saline placebo were
        given to other groups of four monkeys on days 0, 7, and 28. No systemic
        effects were observed. All injection site reactions were mild. All
        vaccines elicited appreciable JE-specific neutralizing antibody
        responses. However, a more rapid increase and higher peak level of
        antibody were seen in the BIKEN group as compared with the NYVAC-JEV and
        ALVAC-JEV groups. The peak neutralizing antibody level in the NYVAC-JEV
        group was higher than that of the ALVAC-JEV group. Antibody persisted in
        all four BIKEN recipients through 273 days of follow-up, whereas, the
        antibody level decreased to the threshold of detection in two NYVAC-JEV
        and all four ALVAC-JEV recipients by day 120. On day 273, all monkeys
        were given a booster dose. A rapid increase in neutralizing antibody was
        seen in all vaccine recipients by seven days. Two months after the
        booster dose, all monkeys were challenged intranasally with one 90%
        effective dose of JE virus. Four recipients of saline, three of
        ALVAC-JEV, one of NYVAC-JEV, and one of BIKEN experienced encephalitis.
        This study suggests that the NYVAC-JEV and ALVAC-JEV vaccines are safe
        and immunogenic in monkeys and that the NYVAC-JEV and BIKEN vaccines are
        effective in protecting monkeys from encephalitis.


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