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Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian–human immunodeficiency virus viraemia with protein/DNA combination

¹ Department of Virology, Biomedical Primate Research Center (BPRC), 2288 GH Rijswijk, The Netherlands
² GlaxoSmithKline Biologicals, Rixensart, Belgium
³ GlaxoSmithKline Biopharmaceuticals CEDD Biology, Stevenage, UK
⁴ Swedish Institute for Infectious Disease Control, Karolinska Institutet, Stockholm, Sweden
⁵ Department of Veterinary Medicine, University of Cambridge, UK

Correspondence
Gerrit Koopman
koopman{at}bprc.nl

Current data suggest that prophylactic human immunodeficiency virus type 1 (HIV) vaccines will be most efficacious if they elicit a combination of adaptive humoral and T-cell responses. Here, we explored the use of different vaccine strategies in heterologous prime–boost regimes and evaluated the breadth and nature of immune responses in rhesus monkeys induced by epidermally delivered plasmid DNA or recombinant HIV proteins formulated in the AS02A adjuvant system. These immunogens were administered alone or as either prime or boost in mixed-modality regimes. DNA immunization alone induced cell-mediated immune (CMI) responses, with a strong bias towards Th1-type cytokines, and no detectable antibodies to the vaccine antigens. Whenever adjuvanted protein was used as a vaccine, either alone or in a regime combined with DNA, high-titre antibody responses to all vaccine antigens were detected in addition to strong Th1- and Th2-type CMI responses. As the vaccine antigens included HIV-1 Env, Nef and Tat, as well as simian immunodeficiency virus (SIV)_mac239 Nef, the animals were subsequently exposed to a heterologous, pathogenic simian–human immunodeficiency virus (SHIV)_89.6p challenge. Protection against sustained high virus load was observed to some degree in all vaccinated groups. Suppression of virus replication to levels below detection was observed most frequently in the group immunized with protein followed by DNA immunization, and similarly in the group immunized with DNA alone. Interestingly, control of virus replication was associated with increased SIV Nef- and Gag-specific gamma interferon responses observed immediately following challenge.

A supplementary figure showing antigen-specific T-cell cytokine responses as measured by intracellular cytokine staining is available with the online version of this paper.