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J Gen Virol 88 (2007), 1-12; DOI 10.1099/vir.0.82493-0

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© 2007 Society for General Microbiology

Review

Clinical experience with plasmid DNA- and modified vaccinia virus Ankara-vectored human immunodeficiency virus type 1 clade A vaccine focusing on T-cell induction

Tomás Hanke, Andrew J. McMichael and Lucy Dorrell

Weatherall Institute of Molecular Medicine, MRC Human Immunology Unit, University of Oxford, The John Radcliffe, Oxford OX3 9DS, UK

Correspondence
Tomás Hanke
tomas.hanke{at}imm.ox.ac.uk

Candidate human immunodeficiency virus type 1 (HIV-1) vaccines focusing on T-cell induction, constructed as pTHr.HIVA DNA and modified vaccinia virus Ankara (MVA).HIVA, were delivered in a heterologous prime–boost regimen. The vaccines were tested in several hundred healthy or HIV-1-infected volunteers in Europe and Africa. Whilst larger trials of hundreds of volunteers suggested induction of HIV-1-specific T-cell responses in <15 % of healthy vaccinees, a series of small, rapid trials in 12–24 volunteers at a time with a more in-depth analysis of vaccine-elicited T-cell responses proved to be highly informative and provided more encouraging results. These trials demonstrated that the pTHr.HIVA vaccine alone primed consistently weak and mainly CD4+, but also CD8+ T-cell responses, and the MVA.HIVA vaccine delivered a consistent boost to both CD4+ and CD8+ T cells, which was particularly strong in HIV-1-infected patients. Thus, whilst the search is on for ways to enhance T-cell priming, MVA is a useful boosting vector for human subunit genetic vaccines.

Published online ahead of print on 5 October 2006 as DOI 10.1099/vir.0.82493-0.




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