title: Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial.
abstract: The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8(+) T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIV(mac251) that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4(+) and CD8(+) T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIV(mac251) acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIV(mac251)-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIV(mac251) infectivity in cells that express high levels of α(4)β(7) integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines.
authors.affiliation: Animal Models and Retroviral Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Poonam
authors.initials: P
authors.lastname: Pegu
authors.forename: Monica
authors.initials: M
authors.lastname: Vaccari
authors.forename: Shari
authors.initials: S
authors.lastname: Gordon
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: Melvin
authors.initials: M
authors.lastname: Doster
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Guan
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Ranajit
authors.initials: R
authors.lastname: Pal
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ferrari
authors.forename: Stephen
authors.initials: S
authors.lastname: Whitney
authors.forename: Lauren
authors.initials: L
authors.lastname: Hudacik
authors.forename: Erik
authors.initials: E
authors.lastname: Billings
authors.forename: Mangala
authors.initials: M
authors.lastname: Rao
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Georgia
authors.initials: G
authors.lastname: Tomaras
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.forename: Claudio
authors.initials: C
authors.lastname: Fenizia
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Donald
authors.initials: D
authors.lastname: Stablein
authors.forename: Jim
authors.initials: J
authors.lastname: Tartaglia
authors.forename: Nelson
authors.initials: N
authors.lastname: Michael
authors.forename: Jerome
authors.initials: J
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D000915:Antibody Affinity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D008251:Macaca; D008562:Membrane Glycoproteins / Q000276:immunology*; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D008562:Membrane Glycoproteins; D018449:SAIDS Vaccines; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus