Phase 1 Safety and Immunogenicity Evaluation of ADMVA, a Multigenic, Modified Vaccinia Ankara-HIV-1 B'/C Candidate Vaccine

• DOI: 10.1371/journal.pone.0008816
• Publication Date: 2010-01-22T23:05:21Z
• Authors: Sandhya Vasan; Sarah J. Schlesinger; Zhiwei Chen; Arlene Hurley; Angela Lombardo; Soe Than; Phumla Adesanya; Catherine Bunce; Mark Boaz; Rosanne Boyle; Eddy Sayeed; Lorna Clark; Daniel Dugin; Mar Boente-Carrera; Claudia Schmidt; Qing Fang; Lei; Yaoxing Huang; Gerasimos J. Zaha...; David F. Gardiner; Marina Caskey; Laura Seamons; Martin Ho; Len Dally; Carol Smith; Josephine Cox; Dilbinder Gill; Jill Gilmour; Michael C. Keefer; Patricia Fast; David D. Ho
• Keywords: Modified vaccinia Ankara; AIDS Vaccines

Background We conducted a Phase I dose-escalation trial of ADMVA, Clade-B'/C-based HIV-1 candidate vaccine expressing env, gag, pol, nef, and tat in modified vaccinia Ankara viral vector. Sequences were derived from prevalent circulating recombinant form Yunnan, China, an area high HIV incidence. The objective was to evaluate the safety immunogenicity ADMVA human volunteers. Methodology/Principal Findings or placebo administered intramuscularly at months 0, 1 6 50 healthy adult volunteers not risk for HIV-1. In each dosage group [1×107 (low), 5×107 (mid), 2.5×108 pfu (high)] randomized 3∶1 ratio receive double-blinded design. Subjects followed local systemic reactogenicity, adverse events including cardiac events, clinical laboratory parameters. Study follow up 18 months. Humoral evaluated by anti-gp120 binding ELISA, immunoflourescent staining, neutralization. Cellular assessed validated IFNγ ELISpot assay intracellular cytokine staining. Anti-vaccinia titers measured ELISA. generally well-tolerated, with no vaccine-related serious events. Local reactogenicity reported 77% 78% volunteers, respectively. majority mild intensity. response rate any antigen 0/12 (0%) group, 3/12 (25%) low 6/12 (50%) mid 8/13 (62%) group. Responses often multigenic occasionally persisted one year post vaccination. Antibodies gp120 detected (0%), (62%), 10/13 (77%) placebo, low, mid, groups, 12 after vaccination, trend toward agreement ability neutralize SF162 vitro. Two mounted antibodies that able clade-matched viruses. Conclusions/Significance well-tolerated elicited durable humoral cellular immune responses. Trial Registration Clinicaltrials.gov NCT00252148