Phase 1 Safety and Immunogenicity Evaluation of a Multiclade HIV‐1 DNA Candidate Vaccine

More than 25 million people have died since HIV/AIDS was identified in 1981, and an estimated 14,000 new infections occur daily [1]. Development of a globally relevant HIV-1 vaccine is critical for controlling this pandemic. The combination of a high transcriptional error rate and frequent recombination results in a remarkable amount of genetic diversity among HIV-1 strains and presents a challenge for selecting vaccine antigens. A joint meeting between the Vaccine Research Center (VRC) (National Institute of Allergy and Infectious Diseases [NIAID], National Institutes of Health [NIH], Department of Health and Human Services) and the Joint United Nations Programme on HIV/AIDS concluded that testing of multiclade candidate vaccines is a high international scientific priority [2]. Sequences encoding gene products from 3 high-incident HIV subtypes were used to produce the candidate vaccine evaluated in the present study [3, 4]. Multiple antigens expressed by the vaccine elicit responses against multiple epitopes and may diminish the chances for immune escape. Delivering antigens by DNA plasmids has potential advantages over other vector delivery systems, notably the lack of antivector immunity. Despite examples of vaccine-induced protection in mice and nonhuman primates [5, 6], DNA immunization has shown limited immunogenicity in humans [7–11]. Here, we report the findings from a phase 1 clinical trial of a multigene, multiclade HIV-1 DNA candidate vaccine and demonstrate the induction of HIV-1–specific T cell and antibody responses.