Broad HIV epitope specificity and viral inhibition induced by multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults
Author(s)
Type
Journal Article
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.
Date Issued
2014-03-07
Date Acceptance
2014-01-29
Citation
PLoS One, 2014, 9, pp.1-10
ISSN
1932-6203
Publisher
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0090378
Start Page
1
End Page
10
Journal / Book Title
PLoS One
Volume
9
Copyright Statement
© 2014 Kopycinski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/24609066
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
IMMUNODEFICIENCY-VIRUS TYPE-1
CYTOTOXIC T-LYMPHOCYTES
ATTENUATED SIV VACCINES
CLINICAL-TRIALS
CELL RESPONSES
INFECTION
VIREMIA
IMMUNODOMINANCE
REPLICATION
ANTIBODIES
AIDS Vaccines
Adenoviridae
Adolescent
Adult
Double-Blind Method
Epitopes
Female
HIV Infections
HIV-1
Humans
Leukocytes, Mononuclear
Male
Middle Aged
Young Adult
Leukocytes, Mononuclear
Humans
Adenoviridae
HIV-1
HIV Infections
AIDS Vaccines
Epitopes
Double-Blind Method
Adolescent
Adult
Middle Aged
Female
Male
Young Adult
General Science & Technology
Publication Status
Published
Date Publish Online
2014-03-07