Article
Author: Cohen, Yehuda Z ; Nkolola, Joseph ; Pegu, Poonam ; Hendriks, Jenny ; Borducchi, Erica N ; Kleinjan, Jane A ; Yanosick, Katherine E ; Gadre, Soniya ; Johnson, Jennifer A ; Moss, Bernard ; Hodin, Caroline ; Nichols, James ; Buleza, Karen ; Kirilova, Marinela ; Rist, Michael ; Zinchuk, Kevin ; Walsh, Stephen R ; Alter, Galit ; Lavine, Christy L ; Robb, Merlin L ; Patel, Alka ; Brandariz, Kara ; Pau, Maria G ; Sarnecki, Michal ; Filter, Rachel D ; Dominguez, David J ; Robles, Alexander ; Seaman, Michael S ; Dolin, Raphael ; Euler, Zelda ; Roten, Raphaele ; Mei, Chun Su ; Tomaka, Frank ; Fredette, Nicholas ; Rao, Mangala ; Baden, Lindsey R ; Weijtens, Mo ; Gothing, Jon A ; Engelson, Brian ; Yuan, Olive ; Ghantous, Fadi ; Liakos, Alexis ; Nijs, Steven ; Kinney, Amy ; Huskens, Gitta ; Ganley, Sarah ; Trinh, Hung V ; Bayne, Madeline ; Abbink, Peter ; Muller, Heidi ; Callewaert, Katleen ; Schuitemaker, Hanneke ; Licona, J Humberto ; Dilan, Rebecca ; LaPorte, Annalena ; Stephens, Faye ; Iampietro, Mark J ; Korber, Bette T ; Michael, Nelson L ; Scheppler, Lorenz ; Peter, Lauren ; Hamel, Robyn ; Cheung, Ann ; Ake, Julie A ; Shields, Jennifer ; Eller, Michael A ; Earl, Patricia L ; Stanley, Kelly A ; Stephenson, Kathryn E ; Garrity, Jetta ; McNally, Anna G ; Barouch, Dan H ; Jennings, Julia ; Zingg, Marshall ; Wajima, Makoto
Background:Mosaic immunogens are bioinformatically engineered human immunodeficiency virus type 1 (HIV-1) sequences designed to elicit clade-independent coverage against globally circulating HIV-1 strains.
Methods:This phase 1, double-blinded, randomized, placebo-controlled trial enrolled healthy HIV-uninfected adults who received 2 doses of a modified vaccinia Ankara (MVA)-vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naive (n = 15) and those who had received an HIV-1 vaccine (Ad26.ENVA.01) 4-6 years earlier (n = 10). We performed prespecified blinded cellular and humoral immunogenicity analyses at days 0, 14, 28, 84, 98, 112, 168, 270, and 365.
Results:All 50 planned vaccinations were administered. Vaccination was safe and generally well tolerated. No vaccine-related serious adverse events occurred. Both cellular and humoral cross-clade immune responses were elicited after 1 or 2 vaccinations in all participants in the HIV-1 vaccine-naive group. Env-specific responses were induced after a single immunization in nearly all subjects who had previously received the prototype Ad26.ENVA.01 vaccine.
Conclusions:No safety concerns were identified, and multiclade HIV-1-specific immune responses were elicited.
Clinical Trials Registration:NCT02218125.