Protection against Friend retrovirus-induced leukemia by recombinant vaccinia viruses expressing the gag gene.
High sequence variability in the envelope gene of human immunodeficiency virus has provoked interest in nonenvelope antigens as potential immunogens against retrovirus infection. However, the role of core protein antigens encoded by the gag gene in protective immunity against retroviruses is unclear. By using recombinant vaccinia viruses expressing the Friend murine leukemia helper virus (F-MuLV) gag gene, we could prime CD4+ T-helper cells and protectively immunize susceptible strains of mice against Friend retrovirus infection. Recovery from leukemic splenomegaly developed more slowly after immunization with vaccinia virus-F-MuLV gag than with vaccinia virus-F-MuLV env; however, genetic nonresponders to the envelope protein could be partially protected with Gag vaccines. Class switching of F-MuLV-neutralizing antibodies from immunoglobulin M to immunoglobulin G after challenge with Friend virus complex was facilitated in mice immunized with the Gag antigen. Sequential deletion of the gag gene revealed that the major protective epitope was located on the N-terminal hydrophobic protein p15.
Miyazawa
M
M
Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840.
Nishio
J
J
Chesebro
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D004279:DNA, Viral; D005260:Female; D005455:Fluorescent Antibody Technique; D005622:Friend murine leukemia virus / Q000235:genetics* / Q000276:immunology; D015870:Gene Expression; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015750:Genes, gag; D007942:Leukemia, Experimental / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics*; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology
D004279:DNA, Viral; D015683:Gene Products, gag; D014614:Vaccines, Synthetic; D014765:Viral Vaccines