Control of HIV-1 replication in vitro by vaccine-induced human CD8(+) T cells through conserved subdominant Pol epitopes

Vaccine
Tina AhmedTomáš Hanke

Abstract

The specificity of CD8(+) T cells is critical for early control of founder/transmitted and reactivated HIV-1. To tackle HIV-1 variability and escape, we designed vaccine immunogen HIVconsv assembled from 14 highly conserved regions of mainly Gag and Pol proteins. When administered to HIV-1-negative human volunteers in trial HIV-CORE 002, HIVconsv vaccines elicited CD8(+) effector T cells which inhibited replication of up to 8 HIV-1 isolates in autologous CD4(+) cells. This inhibition correlated with interferon-γ production in response to Gag and Pol peptide pools, but direct evidence of the inhibitory specificity was missing. Here, we aimed to define through recognition of which epitopes these effectors inhibit HIV-1 replication. CD8(+) T-cells from the 3 broadest HIV-1 inhibitors out of 23 vaccine recipients were expanded in culture by Gag or Pol peptide restimulation and tested in viral inhibition assay (VIA) using HIV-1 clade B and A isolates. Frozen PBMCs were expanded first using peptide pools from Gag or Pol conserved regions and tested on HIV-1-infected cells in VIA or by individual peptides for their effector functions. Single peptide specificities responsible for inhibition of HIV-1 replication were then confirmed by s...Continue Reading

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Citations

Oct 16, 2015·European Journal of Immunology·Nicola TernetteTomáš Hanke
May 20, 2016·Journal of Immunological Methods·Peter StrömMarie Reilly
Oct 21, 2016·Open Forum Infectious Diseases·Héloïse M DelagrèverieJonathan Z Li
Sep 13, 2016·Molecular Therapy. Methods & Clinical Development·Gaudensia MutuaThe Hiv-Core 004 Study Group
Feb 6, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Edmund G WeeTomáš Hanke
Jul 13, 2018·Journal of Virology·Doty B A OjwachJaclyn K Mann
Dec 4, 2019·Expert Review of Vaccines·Iván Del Moral-Sánchez, Kwinten Sliepen
Jun 26, 2021·Molecular Therapy. Methods & Clinical Development·Edmund G WeeTomáš Hanke

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Methods Mentioned

BETA
ELISA
flow cytometry

Software Mentioned

VIA
GraphPad
Gen5
GraphPad Prism
Excel

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