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

Nicola Borthwick, Tina Ahmed, Beatrice Ondondo, Peter Hayes, Annie Rose, Umar Ebrahimsa, Emma Jo Hayton, Antony Black, Anne Bridgeman, Maximillian Rosario, Adrian Vs Hill, Eleanor Berrie, Sarah Moyle, Nicole Frahm, Josephine Cox, Stefano Colloca, Alfredo Nicosia, Jill Gilmour, Andrew J. McMichael, Lucy DorrellTomáš Hanke

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)464-475
Number of pages12
JournalMolecular Therapy
Volume22
Issue number2
DOIs
StatePublished - Feb 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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    Borthwick, N., Ahmed, T., Ondondo, B., Hayes, P., Rose, A., Ebrahimsa, U., Hayton, E. J., Black, A., Bridgeman, A., Rosario, M., Hill, A. V., Berrie, E., Moyle, S., Frahm, N., Cox, J., Colloca, S., Nicosia, A., Gilmour, J., McMichael, A. J., ... Hanke, T. (2014). Vaccine-elicited human T cells recognizing conserved protein regions inhibit HIV-1. Molecular Therapy, 22(2), 464-475. https://doi.org/10.1038/mt.2013.248