Long-term follow up of human T-cell responses to conserved HIV-1 regions elicited by DNA/simian adenovirus/MVA vaccine regimens.

Nathifa Moyo, Nicola Borthwick, Edmund G. Wee, Silvia Capucci, Alison Crook, Lucy Dorrell, Tomáš Hanke

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Abstract

Background

Durability of vaccine-elicited immune responses is one of the key determinants for vaccine success. Our aim is to develop a vaccination strategy against the human immunodeficiency virus type 1 (HIV-1), which induces protective and durable CD8+ T-cell responses. The central theorem of our approach is to focus T cells on highly conserved regions of the HIV-1 proteome and this is achieved through the use of the first-generation conserved vaccine immunogen HIVconsv. This immunogen vectored by plasmid DNA, simian adenovirus and poxvirus MVA was tested in healthy, HIV-1-negative adults in UK and induced high magnitudes of HIVconsv-specific plurifunctional CD8+ T cells capable of in vitro HIV-1 inhibition. Here, we assessed the durability of these responses.

Methods

Vaccine recipients in trial HIV-CORE 002 were invited to provide a blood sample at 1 and 2 years after vaccination. Their PBMCs were tested in IFN-γ ELISPOT, 25-analyte Luminex, CFSE proliferation and intracellular cytokine staining assays, the last enhanced by HLA-peptide dextramer analysis.

Results

12/12 (1 year) and 8/8 (2 years) returning subjects had median (range) of 990 (150–2495) and 763 (70–1745) IFN-γ SFU/106 PBMC specific for HIVconsv, respectively, and recognized 5 (1–6) out of 6 peptide pools at 2 years. Over one-half of the HIVconsv–specific cells expressed at least 3 functions IFN-γ, TNF-α and CD107a, and were capable of proliferation. Among dextramer-reactive cells, naïve, transitional, effector and terminally differentiated memory subsets were similarly represented.

Conclusions

First generation HIVconsv vaccine induced human T cells, which were plurifunctional and persisted for at least 2 years.
Original languageEnglish
Article numbere0181382
JournalP L o S One
Volume12
Issue number7
Number of pages19
ISSN1932-6203
DOIs
Publication statusPublished - 2017
Externally publishedYes

Bibliographical note

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.

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