title: Reduction of anti-HIV-1 Gag immune responses during co-immunization: immune interference by the HIV-1 envelope.
abstract: Immunization with more than one immunogen (co-immunization) is an efficient regimen to induce immunity to multiple antigens. However, immune interference has been reported using multi-plasmid DNA immunizations. HIV-1 envelope (Env) and Gag gene products are the predominant immunogens used in current AIDS vaccines, although, few studies have evaluated possible immune interference when these two antigens are co-administered. Therefore, in this study, immune interference during co-inoculation was examined using DNA vaccines expressing lentiviral Envs and Gag from gene sequences optimized for efficient expression in mammalian cells (codon-optimized). BALB/c mice vaccinated in separate hind legs with each plasmid individually elicited high titer immune responses, however, when HIV-1 Env(gp120) and HIV-1 Gag(p55) DNA plasmids were co-inoculated, there was a reduction in the immune responses elicited to HIV-1 Gag(p55). To determine if the anti-HIV-1 Gag(p55) immune interference was specific to HIV-1 Env(gp120), mice were co-immunized with plasmids expressing the surface envelope protein from two additional lentiviruses, Env(gp130)-SIV or Env(gp90)-EIAV, or a soluble form of hemagglutinin (sHA) from influenza virus and HIV-1 Gag(p55)- or SIV Gag(p55)-DNA. Interestingly, there was no reduction in anti-HIV-1 Gag(p55) immune responses using other lentiviral envelopes or the influenza sHA. Also, none of the lentiviral envelopes reduced anti-SIV Gag(p55) immune responses during co-immunization. Therefore, anti-HIV-1 Gag immune interference appears specific to co-immunizations with HIV-1 Env(gp120) and may involve a yet undefined immunological mechanism(s).
authors.affiliation: Center for Vaccine Research and Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Franklin R
authors.initials: FR
authors.lastname: Toapanta
authors.forename: Jodi K
authors.initials: JK
authors.lastname: Craigo
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Montelaro
authors.forename: Ted M
authors.initials: TM
authors.lastname: Ross
mesh_terms: D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D004336:Drug Antagonism; D005260:Female; D015752:Genes, env / Q000276:immunology*; D015750:Genes, gag / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010957:Plasmids; D019444:Vaccines, DNA / Q000037:antagonists & inhibitors* / Q000276:immunology*
chemical_list: D015699:HIV Envelope Protein gp120; D019444:Vaccines, DNA