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

作者：Lindsey R. Baden, Stephen R. Walsh, Michael S. Seaman, Yehuda Z. Cohen, Jennifer Johnson, J. Humberto Licona, Rachel D Filter, Jane A. Kleinjan, Jon A Gothing, Julia Jennings, Lauren Peter, Joseph P. Nkolola, Peter Abbink, Erica N. Borducchi, Marinela Kirilova, Kathryn E. Stephenson, Poonam Pegu, Michael A. Eller, Hung V. Trinh, Mangala Rao, Julie A. Ake, Michal Sarnecki, Steven Nijs, Katleen Callewaert, Hanneke Schuitemaker, Jenny Hendriks, Maria Grazia Pau, Frank Tomaka, Bette Korber, Galit Alter, Raphael Dolin, Patricia L. Earl, Bernard Moss, Nelson L. Michael, Merlin L. Robb, Dan H. Barouch, IPCAVD006/RV380/HIV-V-A002 Study Group, Alka Patel, Kevin Zinchuk, Alexis Liakos, Brian A. Engelson, Sarah Ganley, Chun Mei, M. Justin Iampietro, Ann Cheung, Kara Brandariz, Annalena LaPorte, Anna G. McNally, Jennifer L. Shields, Kelly Stanley, Rebecca Dilan, Faye Stephens, Robyn Hamel, Madeline Bayne, Katherine E. Yanosick, Alexander Robles, Marshall Zingg, David J. Dominguez, Christy L. Lavine, Garrity Jetta, Michael Rist, Fadi Ghantous, Nicholas Fredette, Karen Buleza, Raphaele Roten, Olive Yuan, Gitta Huskens, Heidi Muller, Zelda Euler, Caroline Hodin, Lorenz Scheppler, Makoto Wajima, Soniya Gadre, James D. Nichols, Amy Kinney, Mo Weijtens · 发表于：The Journal of Infectious Diseases · 年份：2018 · DOI：10.1093/infdis/jiy212 · 被引用次数：45 · 研究领域：HIV Research and Treatment、vaccines and immunoinformatics approaches、Biological Research and Disease Studies

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.