Anti-HIV T cell responses stimulated by DNA and recombinant modified vaccinia virus Ankara vaccines in humans.

PMatilu Mwaua, Inese Ceberea, Julian Suttona, Priscilla Chikotia, Nicola Winstonea, Eduard T.-G. Weea, Tara Beattya, Lucy Dorrella, Helen McShaneb, Claudia Schmidtc, Mary Brooksa, Sandip Patela, Joanna Robertsa, Christopher Conlonb, Sarah Rowland-Jonesa, Job Bwayod, Andrew J McMichaela and Tomas Hankea. aWeatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS (UK); bNuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK; cIAVI, New York, NY, USA; dDepartment of Medical Microbiology, University of Nairobi, Nairobi (Kenya).

Background: The objective of this work was to test the safety and immunogenicity in humans of novel candidate HIV-1 vaccines intended for use in central and eastern Africa. Design: THealthy uninfected human volunteers in UK were immunised with DNA- or Modified vaccinia virus Ankara (MVA)-vectored vaccines on their own or sequentially in a prime boost regimen. The vaccines expressed a common immunogen HIVA, which consists of HIV-1 clade A gag p24/p17 fused to a string of cytotoxic T cell epitopes. Methods: The safety and immunogenicity of candidate pTHr.HIVA DNA and MVA.HIVA vaccines were evaluated over a 6-month period with an additional immunogenicity assessment at 1 year. The induction of T cell responses in peripheral blood was monitored using a validated interferon- ELISPOT assay and confirmed by other sensitive and specific T cell assays. Results: Intramuscular pTHr.HIVA DNA induced responses in 13 out of 18 volunteers, there was no difference between two dosing levels of DNA and some T cell responses tended to develop gradually over six to twelve months after vaccination. Intradermal MVA.HIVA vaccine alone induced HIV-specific T-cell immune responses in 7 out of 8 volunteers that were predominantly mediated by CD8+ T cells. The prime-boost regimen was immunogenic in all 9 tested individuals and induced mixed CD8+ and non-CD8 (CD4+) T cell responses. Conclusion: In these small phase I clinical trials, all three vaccine approaches induced T cell-mediated immune responses. The prime-boost regimen stimulated better quality responses compared to those elicited by either vaccine component alone.