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HIV-1 subtype C Pr55^gag virus-like particle vaccine efficiently boosts baboons primed with a matched DNA vaccine

¹ Medical Virology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch, Cape Town, South Africa
² Institute of Primate Research, PO Box 24481, Karen 00502, Nairobi, Kenya
³ Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Rondebosch, Cape Town, South Africa
⁴ MRC/UCT Liver Research Centre, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Rondebosch, Cape Town, South Africa
⁵ Department of Molecular and Cell Biology, Faculty of Science, University of Cape Town, Rondebosch, Cape Town, South Africa
⁶ National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, Johannesburg, South Africa
⁷ National Health Laboratory Service, Groote Schuur Hospital, Observatory, Cape Town, South Africa

Correspondence
Anna-Lise Williamson
Anna-Lise.Williamson{at}uct.ac.za

A DNA vaccine expressing human immunodeficiency virus type 1 (HIV-1) southern African subtype C Gag (pTHGag) and a recombinant baculovirus Pr55^gag virus-like particle prepared using a subtype C Pr55^gag protein (Gag VLP) was tested in a prime–boost inoculation regimen in Chacma baboons. The response of five baboons to Gag peptides in a gamma interferon (IFN-) enzyme-linked immunospot (ELISPOT) assay after three pTHGag immunizations ranged from 100 to 515 spot-forming units (s.f.u.) per 10⁶ peripheral blood mononuclear cells (PBMCs), whilst the response of two baboons to the Gag VLP vaccine ranged from 415 to 465 s.f.u. per 10⁶ PBMCs. An increase in the Gag-specific response to a range of 775–3583 s.f.u. per 10⁶ PBMCs was achieved by boosting with Gag VLPs the five baboons that were primed with pTHGag. No improvement in Gag responses was achieved in this prime–boost inoculation regimen by increasing the number of pTHGag inoculations to six. IFN- responses were mapped to several peptides, some of which have been reported to be targeted by PBMCs from HIV-1 subtype C-infected individuals. Gag VLPs, given as a single-modality regimen, induced a predominantly CD8⁺ T-cell IFN- response and interleukin-2 was a major cytokine within a mix of predominantly Th1 cytokines produced by a DNA–VLP prime–boost modality. The prime–boost inoculation regimen induced high serum p24 antibody titres in all baboons, which were several fold above that induced by the individual vaccines. Overall, this study demonstrated that these DNA prime/VLP boost vaccine regimens are highly immunogenic in baboons, inducing high-magnitude and broad multifunctional responses, providing support for the development of these products for clinical trials.