Journal Article

First-in-Human Randomized, Controlled Trial of Mosaic HIV-1 Immunogens Delivered via a Modified Vaccinia Ankara Vector

Patel, Alka, Nichols, James, Baden, Lindsey R, Roten, Raphaele, Sarnecki, Michal, Jennings, Julia, Earl, Patricia L, Iampietro, Mark J, Ghantous, Fadi, Kinney, Amy, Zingg, Marshall, Fredette, Nicholas, Euler, Zelda, Yanosick, Katherine E, Lavine, Christy L, Liakos, Alexis, Kleinjan, Jane A, Dolin, Raphael, Filter, Rachel D, Shields, Jennifer, Michael, Nelson L, Bayne, Madeline, Peter, Lauren, Stanley, Kelly A, Weijtens, Mo, Licona, J Humberto, Scheppler, Lorenz, Nijs, Steven, Tomaka, Frank, Gothing, Jon A, Kirilova, Marinela, Pegu, Poonam, Muller, Heidi, Ake, Julie A, Robb, Merlin L, Yuan, Olive, Hodin, Caroline, Rao, Mangala, Zinchuk, Kevin, Dilan, Rebecca, Hendriks, Jenny, LaPorte, Annalena, Ganley, Sarah, Rist, Michael, Walsh, Stephen R, Hamel, Robyn, Gadre, Soniya, Schuitemaker, Hanneke, Korber, Bette T, Barouch, Dan H, Alter, Galit, Dominguez, David J, Cheung, Ann, Stephenson, Kathryn E, Callewaert, Katleen, McNally, Anna G, Brandariz, Kara, Stephens, Faye, Robles, Alexander, Garrity, Jetta, Cohen, Yehuda Z, Buleza, Karen, Pau, Maria G, Abbink, Peter, Trinh, Hung V, Engelson, Brian, Huskens, Gitta, Mei, Chun Su, E

2018

Overview

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. 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. 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. No safety concerns were identified, and multiclade HIV-1-specific immune responses were elicited. NCT02218125.

• Publisher: Oxford University Press
• Subject: Adult / AIDS Vaccines - administration & dosage / AIDS Vaccines - adverse effects / AIDS Vaccines - genetics / AIDS Vaccines - immunology / Double-Blind Method / Drug Carriers / Drug-Related Side Effects and Adverse Reactions - epidemiology / Drug-Related Side Effects and Adverse Reactions - pathology / Female / Genetic Vectors / HIV Infections - prevention & control / HIV-1 - immunology / Humans / Immunity, Cellular / Immunity, Humoral / Longitudinal Studies / Major and Brief Reports / Male / Middle Aged / Placebos - administration & dosage / Treatment Outcome / Vaccines, Subunit - administration & dosage / Vaccines, Subunit - adverse effects / Vaccines, Subunit - genetics / Vaccines, Subunit - immunology / Vaccines, Synthetic - administration & dosage / Vaccines, Synthetic - adverse effects / Vaccines, Synthetic - genetics / Vaccines, Synthetic - immunology / Vaccinia virus - genetics / Young Adult