Title Phase I safety and immunogenicity evaluation of ADVAX , aMultigenic , DNA-based Clade C / B ' HIV-1 candidate vaccine

Background: We conducted a Phase I dose escalation trial of ADVAX, a DNA-based candidate HIV-1 vaccine expressing Clade C/B’ env, gag, pol, nef, and tat genes. Sequences were derived from a prevalent circulating recombinant form in Yunnan, China, an area of high HIV-1 incidence. The objective was to evaluate the safety and immunogenicity of ADVAX in human volunteers. Methodology/Principal Findings: ADVAX or placebo was administered intramuscularly at months 0, 1 and 3 to 45 healthy volunteers not at high risk for HIV-1. Three dosage levels [0.2 mg (low), 1.0 mg (mid), and 4.0 mg (high)] were tested. Twelve volunteers in each dosage group were assigned to receive ADVAX and three to receive placebo in a double-blind design. Subjects were followed for local and systemic reactogenicity, adverse events, and clinical laboratory parameters. Study follow up was 18 months. Humoral immunogenicity was evaluated by anti-gp120 binding ELISA. Cellular immunogenicity was assessed by a validated IFNc ELISpot assay and intracellular cytokine staining. ADVAX was safe and well-tolerated, with no vaccine-related serious adverse events. Local and systemic reactogenicity events were reported by 64% and 42% of vaccine recipients, respectively. The majority of events were mild. The IFNc ELISpot response rates to any HIV antigen were 0/9 (0%) in the placebo group, 3/12 (25%) in the low-dosage group, 4/12 (33%) in the mid-dosage group, and 2/12 (17%) in the high-dosage group. Overall, responses were generally transient and occurred to each gene product, although volunteers responded to single antigens only. Binding antibodies to gp120 were not detected in any volunteers, and HIV seroconversion did not occur. Conclusions/Significance: ADVAX delivered intramuscularly is safe, well-tolerated, and elicits modest but transient cellular immune responses. Trial Registration: Clinicaltrials.gov NCT00249106 Citation: Vasan S, Schlesinger SJ, Huang Y, Hurley A, Lombardo A, et al. (2010) Phase 1 Safety and Immunogenicity Evaluation of ADVAX, a Multigenic, DNABased Clade C/B’ HIV-1 Candidate Vaccine. PLoS ONE 5(1): e8617. doi:10.1371/journal.pone. 0008617 Editor: Sean Emery, University of New South Wales, Australia Received June 22, 2009; Accepted November 11, 2009; Published January 25, 2010 Copyright: 2010 Vasan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Funding for this study was provided by the International AIDS Vaccine Initiative (IAVI) and its donors, including the generous support of the American people through the United States for International Development (USAID). IAVI played a direct role in study design, data collection and analysis, decision to publish, and preparation of this manuscript. Support was also provided by the Rockefeller University and University of Rochester Clinical and Translational Science Awards. Competing Interests: The authors have declared that no competing interests exist. * E-mail: svasan@adarc.org ¤a Current address: AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People’s Republic of China ¤b Current address: Pfizer Inc, New York, New York, United States of America ¤c Current address: Novartis Pharmaceuticals, Basel, Switzerland ¤d Current address: Sanofi Pasteur, Swiftwater, Pennsylvania, United States of America