Characterization of Humoral and Cellular Immune Responses Elicited by a Recombinant Adenovirus Serotype 26 HIV-1 Env Vaccine in Healthy Adults (IPCAVD 001)

(See the major article by Baden et al, on pages 240–7.) The development of a safe and effective human immunodeficiency virus type (HIV-1) vaccine is an urgent biomedical priority. Only 3 HIV-1 vaccine concepts have completed clinical efficacy testing to date [1–4], suggesting that additional HIV-1 vaccine candidates need to be explored in clinical trials [5–7]. It is important to understand the humoral and cellular immunogenicity profiles of HIV-1 vaccine candidates in humans to inform clinical development of novel vaccine vectors and vaccine strategies. The failure of the Merck Ad5-gag/pol/nef vaccine in the phase 2b Step Study [3, 8] was a disappointment to the HIV-1 vaccine field but led to the development of alternative serotype adenovirus (Ad) vectors that may offer benefits over Ad5 vectors [9, 10]. Ad serotype 26 (Ad26) is a novel vector that shows substantial differences from Ad5 in several biologic characteristics, including seroepidemiology, cellular receptor use, in vivo tropism, innate immune profiles, adaptive immune phenotypes, and protective efficacy in rhesus monkeys [11–19]. In particular, Ad26 vectors combined with other Ad or poxvirus vectors have afforded partial protective efficacy against both acquisition of infection and virologic control following heterologous SIVmac251 challenges in rhesus monkeys [19]. In an accompanying manuscript [20], we describe the primary safety and immunogenicity results of the Integrated Preclinical/Clinical AIDS Vaccine Development Program (IPCAVD) 001 trial, a randomized, double-blinded, placebo-controlled, first-in-human phase 1 clinical trial of a prototype Ad26 vector–based vaccine expressing clade A HIV-1 Env (Ad26.ENVA.01). Ad26.ENVA.01 proved safe and immunogenic in healthy, Ad26-seronegative, HIV-1–uninfected subjects, and Env-specific humoral and cellular immune responses were assessed by enzyme-linked immunosorbent assays (ELISAs) and interferon γ (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assays [20]. Here, we report a detailed characterization of humoral and cellular immune responses elicited by Ad26.ENVA.01 in humans in the IPCAVD 001 trial. Humoral immune responses were assessed by linear peptide arrays to evaluate magnitude, breadth, and epitopic diversity of Env-specific binding antibody responses and by functional nonneutralizing antibody assays. Cellular immune responses were assessed by epitope mapping, multiparameter intracellular cytokine staining (ICS) assays, and cytokine multiplex bead arrays. These data demonstrate the broad diversity of immune responses and the unique immunologic profile induced by this vaccine.