VACCINIA VIRUS RECOMBINANTS EXPRESSING CHIMERIC PROTEINS OF HUMAN-IMMUNODEFICIENCY-VIRUS AND GAMMA INTERFERON ARE ATTENUATED FOR NUDE-MICE

被引:53
作者
GIAVEDONI, LD
JONES, L
GARDNER, MB
GIBSON, HL
NG, CTL
BARR, PJ
YILMA, T
机构
[1] UNIV CALIF DAVIS,DEPT VET MICROBIOL & IMMUNOL,MOLEC BIOL TROP DIS AGENTS LAB,DAVIS,CA 95616
[2] CHIRON CORP,DEPT MOLEC BIOL,EMERYVILLE,CA 94608
[3] UNIV CALIF DAVIS,DEPT MED PATHOL,DAVIS,CA 95616
关键词
CHIMERIC PROTEINS; LYMPHOKINES; VACCINE DEVELOPMENT;
D O I
10.1073/pnas.89.8.3409
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have developed a method for attenuating vaccinia virus recombinants by expressing a fusion protein of a lymphokine and an immunogen. Chimeric genes were constructed that coded for gamma-interferon (IFN-gamma) and structural proteins of the human immunodeficiency virus type 1 (HIV-1). In this study, we describe the biological and immunological properties of vaccinia virus recombinants expressing chimeric genes of murine or human IFN-gamma with glycoprotein gp120, gag, and a fragment of gp41. All fusion proteins retained the antigenic characteristics of both IFN-gamma and HIV as shown by immunoblot analysis. However, the antiviral activity of IFN-gamma could be demonstrated only for the IFN-gamma-gag fusion protein. In contrast, the attenuating activity of IFN-gamma for nude mice was retained by all of the recombinants, albeit at various rates. Unlike the antiviral activity, the attenuating activity of IFN-gamma was not species specific. Implications for the development of attenuated live recombinant vaccines for AIDS are discussed.
引用
收藏
页码:3409 / 3413
页数:5
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