Co-Administration of HIV Env Protein with DNA and/or NYVAC Vaccines in Humans Results in Earlier and Potent Generation of Anti-Env Antibody Responses

Background: The immunization regimens evaluated to date in the development of HIV vaccines have included purified Env protein vaccines as a part of the boosting components of the vaccination regimen. In the present study, we tested the hypothesis that the co-administration of Env protein with either DNA or NYVAC vector vaccines during the priming results in early generation of antibody responses to the Env V1/V2 region that are important markers for effective protection against infection. This study evaluated a multicomponent HIV vaccine including as immunogens either DNA or NYVAC vectors alone or in combination with Env protein, followed by a co-delivered NYVAC/protein boost.   Methods: Ninety-six HIV-1 uninfected subjects were randomized in this double-blind placebo-controlled phase 1b human clinical trial to receive 2x NYVAC followed by 2x NYVAC+AIDSVAX® B/E (n = 20); 4x NYVAC+AIDSVAX® B/E (n = 20); 2x DNA followed by 2x NYVAC+AIDSVAX® B/E (n = 20); 2x DNA+AIDSVAX® B/E followed by 2x NYVAC+AIDSVAX® B/E (n = 20); or placebo (n = 16). Immune response measures included cross-clade and epitopespecific binding antibodies, neutralizing antibodies (nAb), and antibody dependent cell-mediated cytotoxicity (ADCC). Findings: IgG response rates were 74-95% at 2 weeks post 4th vaccination across study groups. Early administration of the gp120 protein was associated with a markedly earlier and higher AUC for gp120 binding, anti-V1V2, neutralizing antibody, and with better antibody response coverage over a period of 18 months than the regimens delaying the gp120 protein until the 6 month vaccination   Interpretation: Co-administration of AIDSVAX® B/E gp120 protein components with DNA and/or NYVAC vectors during priming results in early and potent induction of Env V1/V2 IgG binding antibody responses, markers associated with reduced risk of infection in a previous efficacy trial. This immunization approach should be considered for induction of preventative antibodies in future HIV vaccine efficacy trials. Trial Registration: ClinicalTrials.gov: NCT01799954. Funding Statement: UM1 AI068614, UM1 AI068635, UM1 AI068618 and UM1 AI069481. Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: The study protocol was approved by the institutional ethics committee of the Centre Hospitalier Universitaire Vaudois (CHUV) (Lausanne, Switzerland) and by Swissmedic, the Swiss Agency for Therapeutic Products (Bern, Switzerland). All study participants provided written informed consent prior to participation.