First-in-Human Randomized, Controlled Trial of Mosaic HIV-1 Immunogens Delivered via a Modified Vaccinia Ankara Vector
Lindsey R Baden, Stephen R Walsh, Michael S Seaman, Yehuda Z Cohen, Jennifer A Johnson, J Humberto Licona, Rachel D Filter, Jane A Kleinjan, Jon A Gothing, Julia Jennings, Lauren Peter, Joseph 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 G Pau, Frank Tomaka, Bette T 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 Engelson, Sarah Ganley, Chun Su Mei, Mark J Iampietro, Ann Cheung, Kara Brandariz, Annalena LaPorte, Anna G McNally, Jennifer Shields, Kelly A Stanley, Rebecca Dilan, Faye Stephens, Robyn Hamel, Madeline Bayne, Katherine E Yanosick, Alexander Robles, Marshall Zingg, David J Dominguez, Christy L Lavine, Jetta Garrity, 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 Nichols, Amy Kinney, Mo Weijtens, Lindsey R Baden, Stephen R Walsh, Michael S Seaman, Yehuda Z Cohen, Jennifer A Johnson, J Humberto Licona, Rachel D Filter, Jane A Kleinjan, Jon A Gothing, Julia Jennings, Lauren Peter, Joseph 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 G Pau, Frank Tomaka, Bette T 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 Engelson, Sarah Ganley, Chun Su Mei, Mark J Iampietro, Ann Cheung, Kara Brandariz, Annalena LaPorte, Anna G McNally, Jennifer Shields, Kelly A Stanley, Rebecca Dilan, Faye Stephens, Robyn Hamel, Madeline Bayne, Katherine E Yanosick, Alexander Robles, Marshall Zingg, David J Dominguez, Christy L Lavine, Jetta Garrity, 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 Nichols, Amy Kinney, Mo Weijtens
Abstract
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.
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Source: PubMed