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Mol Ther. 2014 Feb;22(2):464-475. doi: 10.1038/mt.2013.248. Epub 2013 Oct 31.

Vaccine-elicited human T cells recognizing conserved protein regions inhibit HIV-1.

Author information

1
The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK.
2
The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK.
3
IAVI Human Immunology Laboratory, Imperial College, London, UK.
4
Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Churchill Hospital, Oxford, UK.
5
Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Churchill Hospital, Oxford, UK; Current address: Institut Pasteur du Laos, Vientiane, Laos People's Democratic Republic.
6
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK; Current address: Medical Microbiology and Immunology, Li Ka Shing Institute of Virology, 6-096 Katz Centre for Health Research, Edmonton, Alberta, Canada.
7
The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK; Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Churchill Hospital, Oxford, UK; Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital, Oxford, UK.
8
Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital, Oxford, UK.
9
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
10
Okairos, Rome, Italy.
11
Okairos, Rome, Italy; CEINGE, Naples, Italy; Department of Biochemistry and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
12
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK.
13
The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK; Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Churchill Hospital, Oxford, UK; Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital, Oxford, UK. Electronic address: tomas.hanke@ndm.ox.ac.uk.

Abstract

Virus diversity and escape from immune responses are the biggest challenges to the development of an effective vaccine against HIV-1. We hypothesized that T-cell vaccines targeting the most conserved regions of the HIV-1 proteome, which are common to most variants and bear fitness costs when mutated, will generate effectors that efficiently recognize and kill virus-infected cells early enough after transmission to potentially impact on HIV-1 replication and will do so more efficiently than whole protein-based T-cell vaccines. Here, we describe the first-ever administration of conserved immunogen vaccines vectored using prime-boost regimens of DNA, simian adenovirus and modified vaccinia virus Ankara to uninfected UK volunteers. The vaccine induced high levels of effector T cells that recognized virus-infected autologous CD4(+) cells and inhibited HIV-1 replication by up to 5.79 log10. The virus inhibition was mediated by both Gag- and Pol- specific effector CD8(+) T cells targeting epitopes that are typically subdominant in natural infection. These results provide proof of concept for using a vaccine to target T cells at conserved epitopes, showing that these T cells can control HIV-1 replication in vitro.

PMID:
24166483
PMCID:
PMC3911893
DOI:
10.1038/mt.2013.248
[Indexed for MEDLINE]
Free PMC Article

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