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

Tomá Hanke

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

Correspondence
Tomá 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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