Vaccine Treatment for HIV-Infection

Study Design: This is a Phase I open-label study to examine safety, tolerability and immune response of a multiclade HIV adenoviral vector vaccine as a booster vaccination in uninfected adults. The hypothesis is that this vaccine will be safe as a booster vaccine and elicit immune responses to HIV. The primary objective is to evaluate the safety and tolerability of a VRC-HIVADV014-00-VP booster vaccination in uninfected subjects who previously received 3 injections of VRC-HIVDNA016-00-VP. The secondary objectives include immunogenicity evaluations, adenovirus serotype 5 (Ad5) antibody titers, and social impacts. Exploratory evaluations include epitope mapping and other immunogenicity evaluations. Product Description: VRC-HIVADV014-00-VP (rAd) is a recombinant product composed of 4 adenoviral vectors (in a 3:1:1:1 ratio) that encode the HIV-1 Gag/Pol polyprotein from clade B and HIV-1 Env glycoproteins from clades A, B, and C, respectively. Subjects: Healthy adult volunteers who previously received three injections of VRC-HIVDNA016-00-VP at a dosage of 4 mg in the VRC 007 study (04-I-0254). The subjects in these groups were between 20 and 36 years old at time of enrollment in VRC 007; those who participate in VRC 010 will be no more than 36 weeks older at the time of enrollment into VRC 010. Study Plan: Up to fourteen volunteers will receive one 1 mL injection of the study agent at a dosage of 1010 particle units (PU) intramuscularly (IM) in a deltoid muscle. Safety and immunogenicity will be evaluated by follow-up visits over the subsequent 24 weeks. The peripheral blood mononuclear cell (PBMC) sample for immunogenicity studies collected at Week 4 after vaccination will be obtained by apheresis if the subject is willing and eligible for apheresis and an apheresis appointment can be conveniently scheduled in the interval specified; otherwise PBMCs will be obtained from 80 mL blood collected by phlebotomy. Study Duration: Subjects will be evaluated at 6 or more clinical visits for 24 weeks after the study injection. Study Endpoints: The primary endpoint is safety of the vaccine administered at a dose of 10(10) PU by IM injection. Secondary endpoints are immunogenicity as indicated by HIV-specific antibody through Week 4, cellular immune responses through Week 6, Ad5 antibody titer at Week 0 and Week 4 and social impact at Week 24. Exploratory analyses include immunogenicity at Weeks 12 and 24, Ad5 antibody titer at Week 24 and epitope mapping of the CD8+ and CD4+ T cell responses at Week 4.