title: Improved protection of rhesus macaques against intrarectal simian immunodeficiency virus SIV(mac251) challenge by a replication-competent Ad5hr-SIVenv/rev and Ad5hr-SIVgag recombinant priming/gp120 boosting regimen.
abstract: In this study we investigated the ability of a replication-competent Ad5hr-SIVenv/rev and Ad5hr-SIVgag recombinant priming/gp120 boosting regimen to induce protective immunity in rhesus macaques against pathogenic simian immunodeficiency virus(mac251). Immunization of macaques by two sequential administrations of the same recombinants by the same route resulted in boosting and persistence of SIV-specific cellular immune responses for 42 weeks past the initial immunization. Anti-SIV gp120 immunoglobulin G (IgG) and IgA antibodies were induced in secretory fluids, and all macaques exhibited serum neutralizing antibody activity. After intrarectal SIV(mac251) challenge, all of the macaques became infected. However, relative protection, as assessed by statistically significant lower SIV viral loads in plasma at both acute infection and set point, was observed in 8 out of 12 immunized non-Mamu-A(*)01 animals. Elevated mean cellular immune responses to Gag and Env, neutralizing antibody activity, and IgG and IgA binding antibody levels were observed in the eight protected macaques. Statistically significant correlations with protective outcome were observed for cellular immune responses to SIV Env and Gag and for SIV gp120-specific IgG antibodies in nasal and vaginal fluids. Two macaques that exhibited the greatest and most persistent viremia control also exhibited strong CD8(+) T-cell antiviral activity. The results suggest that a spectrum of immune responses may be necessary for adequate control of viral replication and disease progression and highlight a potential role for nonneutralizing antibodies at mucosal sites.
authors.affiliation: Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Joel
authors.initials: J
authors.lastname: Pinczewski
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gómez-Román
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: V S
authors.initials: VS
authors.lastname: Kalyanaraman
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Markham
authors.forename: Kristine
authors.initials: K
authors.lastname: Aldrich
authors.forename: Matthew
authors.initials: M
authors.lastname: Moake
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Yuanmei
authors.initials: Y
authors.lastname: Lou
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000285:Administration, Rectal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015694:Gene Products, rev / Q000235:genetics / Q000276:immunology; D018928:Immunity, Mucosal; D007114:Immunization; D007117:Immunization, Secondary; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D012367:RNA, Viral / Q000097:blood; D011995:Recombination, Genetic; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015694:Gene Products, rev; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C069623:gp120 protein, Simian immunodeficiency virus