@article{4bd928345451415eaa95df8c02768dea,
title = "Vaccine-elicited human T cells recognizing conserved protein regions inhibit HIV-1",
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 log 10. 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.",
author = "Nicola Borthwick and Tina Ahmed and Beatrice Ondondo and Peter Hayes and Annie Rose and Umar Ebrahimsa and Hayton, {Emma Jo} and Antony Black and Anne Bridgeman and Maximillian Rosario and Hill, {Adrian Vs} and Eleanor Berrie and Sarah Moyle and Nicole Frahm and Josephine Cox and Stefano Colloca and Alfredo Nicosia and Jill Gilmour and McMichael, {Andrew J.} and Lucy Dorrell and Tom{\'a}{\v s} Hanke",
note = "Funding Information: The authors thank the volunteers for making this study possible. The work was supported by Medical Research Council (MRC) UK and Department for International Development UK through an Experimental Medicine call II award G0701669 with contributions from the International AIDS Vaccine Initiative. HIV-1 infectious molecular clones were obtained from Dr George Shaw, University of Pennsylvania. The FEC Control Peptide Pool was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH (ref. no. 19626). A.N. and S.C. who were employees and shareholders of Okairos and Advent during the conduct of the study, and are inventors on patents WO 2005071093 (A3), WO 2006133911 (A3) and WO 03031588 (A2), A.J.McM. who reports grants from MRC and NIH, personal fees from International AIDS Vaccine Initiative SAB during the conduct of the study and is an inventor on patent WO 06123256, LC reports grants from MRC during the conduct of the study, and T.H. who reports grants from MRC and European and Developing Countries Clinical Trial Partnership obtained during the conduct of the study and is an inventor on patent WO 06123256. The other authors declare no conflict of interest.",
year = "2014",
month = feb,
doi = "10.1038/mt.2013.248",
language = "English (US)",
volume = "22",
pages = "464--475",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "2",
}