title: Critical role for Env as well as Gag-Pol in control of a simian-human immunodeficiency virus 89.6P challenge by a DNA prime/recombinant modified vaccinia virus Ankara vaccine.
abstract: Cellular immune responses against epitopes in conserved Gag and Pol sequences of human immunodeficiency virus type 1 have become popular targets for candidate AIDS vaccines. Recently, we used a simian-human immunodeficiency virus model (SHIV 89.6P) with macaques to demonstrate the control of a pathogenic mucosal challenge by priming with Gag-Pol-Env-expressing DNA and boosting with Gag-Pol-Env-expressing recombinant modified vaccinia virus Ankara (rMVA). Here we tested Gag-Pol DNA priming and Gag-Pol rMVA boosting to evaluate the contribution of anti-Env immune responses to viral control. The Gag-Pol vaccine raised frequencies of Gag-specific T cells similar to those raised by the Gag-Pol-Env vaccine. Following challenge, these rapidly expanded to counter the challenge infection. Despite this, the control of the SHIV 89.6P challenge was delayed and inconsistent in the Gag-Pol-vaccinated group and all of the animals underwent severe and, in most cases, sustained loss of CD4(+) cells. Interestingly, most of the CD4(+) cells that were lost in the Gag-Pol-vaccinated group were uninfected cells. We suggest that the rapid appearance of binding antibody for Env in Gag-Pol-Env-vaccinated animals helped protect uninfected CD4(+) cells from Env-induced apoptosis. Our results highlight the importance of immune responses to Env, as well as to Gag-Pol, in the control of immunodeficiency virus challenges and the protection of CD4(+) cells.
authors.affiliation: Vaccine Research Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
authors.forename: James M
authors.initials: JM
authors.lastname: Smith
authors.forename: Silvija I
authors.initials: SI
authors.lastname: Staprans
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: John D
authors.initials: JD
authors.lastname: Altman
authors.forename: Shawn P
authors.initials: SP
authors.lastname: O'Neil
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Kozyr
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wyatt
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.forename: James G
authors.initials: JG
authors.lastname: Herndon
authors.forename: Janet M
authors.initials: JM
authors.lastname: McNicholl
authors.forename: Harold M
authors.initials: HM
authors.lastname: McClure
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.forename: Harriet L
authors.initials: HL
authors.lastname: Robinson
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015685:Fusion Proteins, gag-pol / Q000276:immunology*; D015686:Gene Products, env / Q000276:immunology*; D006678:HIV / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015685:Fusion Proteins, gag-pol; D015686:Gene Products, env; D015483:HIV Antibodies; D019444:Vaccines, DNA