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Induction of Broad Cross-Subtype-Specific HIV-1 Immune Responses by a Novel Multivalent HIV-1 Peptide Vaccine in Cynomolgus Macaques

Ali Azizi^*,, David E. Anderson^*,¶, José V. Torres^*,, Andrei Ogrel^*, Masoud Ghorbani^*, Catalina Soare^*,, Paul Sandstrom, Jocelyne Fournier and Francisco Diaz-Mitoma^1,*,

^* Variation Biotechnologies, Ottawa, Ontario, Canada; Division of Virology and Molecular Immunology, Department of Pathology and Laboratory Medicine, University of Ottawa and Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada; Department of Medical Microbiology and Immunology, Davis School of Medicine, University of California, Davis, CA 95616; Division of HIV, Public Health Agency of Canada, Ottawa, Ontario, Canada; and ^¶ Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115

One of the major obstacles in the design of an effective vaccine against HIV-1 is its antigenic variation, which results in viral escape from the immune system. Through a bioinformatics approach, we developed an innovative multivalent HIV-1 vaccine comprised of a pool of 176 lipidated and nonlipidated peptides representing variable regions of Env and Gag proteins. The potency and breadth of the candidate vaccine against a panel of HIV-1 subtypes was evaluated in nonhuman primate (cynomolgus macaques) and humanized mouse (HLA-A2.1) models. The results demonstrate strong immunogenicity with both breadth (humoral and cellular immunity) and depth (immune recognition of widely divergent viral sequences) against heterologous HIV-1 subtypes A–F.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Francisco Diaz-Mitoma, Division of Virology and Molecular Immunology, Research Institute, Children’s Hospital of Eastern Ontario, 401 Smyth, Ottawa, Ontario, K1H 8L1, Canada. E-mail address: diaz{at}cheo.on.ca

² Abbreviations used in this paper: Nab, neutralizing Ab; DP, double positive; TCLA, T cell line adapted; TFA, trifluoroacetic acid; rVV, recombinant vaccinia virus; ICS, intracellular cytokine staining; FCS, forward scatter; SSC, side scatter; SI, stimulation index; SFC, spot-forming cell; EM, effector memory; CM, central memory; SP, single positive; RLU, relative luminescence unit; SHIV, simian HIV; aa, amino acid.