Vaccinia virus recombinants expressing chimeric proteins of human immunodeficiency virus and gamma interferon are attenuated for nude mice.
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.
Giavedoni
L D
LD
Department of Veterinary Microbiology and Immunology, University of California, Davis 95616.
Jones
L
L
Gardner
M B
MB
Gibson
H L
HL
Ng
C T
CT
Barr
P J
PJ
Yilma
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002678:Chimera; D005813:Genes, Synthetic; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D012689:Sequence Homology, Nucleic Acid; D014613:Vaccines, Attenuated; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*
D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D014613:Vaccines, Attenuated; D015678:Viral Structural Proteins; D007371:Interferon-gamma