title: Broad HIV epitope specificity and viral inhibition induced by multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults.
abstract: A correlation between in vivo and in vitro virus control mediated by CD8+ T-cell populations has been demonstrated by CD8 T-cell-mediated inhibition of HIV-1 and SIV replication in vitro in peripheral blood mononuclear cells (PBMCs) from infected humans and non-human primates (NHPs), respectively. Here, the breadth and specificity of T-cell responses induced following vaccination with replication-defective adenovirus serotype 35 (Ad35) vectors containing a fusion protein of Gag, reverse transcriptase (RT), Integrase (Int) and Nef (Ad35-GRIN) and Env (Ad35-ENV), derived from HIV-1 subtype A isolates, was assessed in 25 individuals. The vaccine induced responses to a median of 4 epitopes per vaccinee. We correlated the CD8 responses to conserved vs. variable regions with the ability to inhibit a panel of 7 HIV-1 isolates representing multiple clades in a virus inhibition assay (VIA). The results indicate that targeting immunodominant responses to highly conserved regions of the HIV-1 proteome may result in an increased ability to inhibit multiple clades of HIV-1 in vitro. The data further validate the use of the VIA to screen and select future HIV vaccine candidates. Moreover, our data suggest that future T cell-focused vaccine design should aim to induce immunodominant responses to highly conserved regions of the virus.
authors.affiliation: International AIDS Vaccine Initiative (IAVI), Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Jakub
authors.initials: J
authors.lastname: Kopycinski
authors.affiliation: International AIDS Vaccine Initiative (IAVI), Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Hayes
authors.affiliation: International AIDS Vaccine Initiative (IAVI), Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Ambreen
authors.initials: A
authors.lastname: Ashraf
authors.affiliation: International AIDS Vaccine Initiative (IAVI), Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Hannah
authors.initials: H
authors.lastname: Cheeseman
authors.affiliation: International AIDS Vaccine Initiative (IAVI), Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lala
authors.affiliation: International AIDS Vaccine Initiative (IAVI), Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Justyna
authors.initials: J
authors.lastname: Czyzewska-Khan
authors.affiliation: International AIDS Vaccine Initiative (IAVI), Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Spentzou
authors.affiliation: International AIDS Vaccine Initiative (IAVI), Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Dilbinder K
authors.initials: DK
authors.lastname: Gill
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.affiliation: IAVI, New York, New York, United States of America.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Excler
authors.affiliation: IAVI, New York, New York, United States of America.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fast
authors.affiliation: International AIDS Vaccine Initiative (IAVI), Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Josephine
authors.initials: J
authors.lastname: Cox
authors.affiliation: International AIDS Vaccine Initiative (IAVI), Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology* / Q000627:therapeutic use; D000256:Adenoviridae / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes