Phase 1 Safety and Immunogenicity Evaluation of ADVAX, a Multigenic, DNA-Based Clade C/B' HIV-1 Candidate Vaccine

• DOI: 10.1371/journal.pone.0008617
• Publication Date: 2010-01-22T23:05:16Z
• Authors: Sandhya Vasan; Sarah J. Schlesinger; Yaoxing Huang; Arlene Hurley; Angela Lombardo; Zhiwei Chen; Soe Than; Phumla Adesanya; Catherine Bunce; Mark Boaz; Rosanne Boyle; Eddy Sayeed; Lorna Clark; Daniel Dugin; Claudia Schmidt; Yang Song; Laura Seamons; Len Dally; Martin Ho; Carol Smith; Martin Markowitz; Josephine Cox; Dilbinder K. Gill; Jill Gilmour; Michael C. Keefer; Patricia Fast; David D. Ho
• Keywords: Reactogenicity; ELISPOT; HIV vaccine; AIDS Vaccines

Background We conducted a Phase I dose escalation trial of ADVAX, DNA-based candidate HIV-1 vaccine expressing Clade C/B' env, gag, pol, nef, and tat genes. Sequences were derived from prevalent circulating recombinant form in Yunnan, China, an area high incidence. The objective was to evaluate the safety immunogenicity ADVAX human volunteers. Methodology/Principal Findings or placebo administered intramuscularly at months 0, 1 3 45 healthy volunteers not risk for HIV-1. Three dosage levels [0.2 mg (low), 1.0 (mid), 4.0 (high)] tested. Twelve each group assigned receive three double-blind design. Subjects followed local systemic reactogenicity, adverse events, clinical laboratory parameters. Study follow up 18 months. Humoral evaluated by anti-gp120 binding ELISA. Cellular assessed validated IFNγ ELISpot assay intracellular cytokine staining. safe well-tolerated, with no vaccine-related serious events. Local reactogenicity events reported 64% 42% recipients, respectively. majority mild. response rates any HIV antigen 0/9 (0%) group, 3/12 (25%) low-dosage 4/12 (33%) mid-dosage 2/12 (17%) high-dosage group. Overall, responses generally transient occurred gene product, although responded single antigens only. Binding antibodies gp120 detected volunteers, seroconversion did occur. Conclusions/Significance delivered is safe, elicits modest but cellular immune responses. Trial Registration Clinicaltrials.gov NCT00249106