Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine
Joseph P. Casazza, Amelia R. Hofstetter, Pamela Costner, LaSonji A Holman, Cynthia S. Hendel, Alicia T. Widge, Richard L Wu, William R Whalen, Jennifer Cunningham, Anita Arthur, Xiaolin Wang, Abidemi Ola, Jamie Saunders, Floreliz Mendoza, Laura Novik, Maria Claudia Burgos Florez, Ana M. Ortega‐Villa, Preeti Apte, Larisa Strom, Lu Wang, Marjaan Imam, Manjula Basappa, Mursal Naisan, Mike Castro, Jessica F. Trost, Sandeep Narpala, Hillary A. Vanderven, Galina V. Yamshchikov, Nina M. Berkowitz, Ingelise J. Gordon, Sarah H. Plummer, Diane Wycuff, Sandra Vazquez, Rebecca A. Gillespie, Adrian Creanga, William C. Adams, Kevin Carlton, Jason G. Gall, Adrian B. McDermott, Leonid Serebryannyy, Katherine V. Houser, Richard A. Koup, Barney S. Graham, Julie E. Ledgerwood, John R. Mascola, Theodore C. Pierson, Sarah F. Andrews, Masaru Kanekiyo, Lesia Dropulic, The VRC 323 study team, Akuah Abrah, Seemal F. Awan, Obrimpong Amoa-Awua, Martin Apgar, Allison Beck, Katherine Brooks, Tommy Bruington, Eugenia Burch, Chris Case, Emily E. Coates, Erykah Coe, Aba M. Eshun, Martin R. Gaudinski, Renunda Dyer, Lam Le, Brenda Larkin, John Misasi, Patricia Morgan, Allen Mueller, Thuy Nguyen, Mark O’Callahan, Amine Ourahmane, Karen M. Parker, Iris Pittman, Matthew Reiber, LaShawn Requilman, Geoffrey Shimberg, Rosa Silva, Judy Stein, Shinyi Telscher, Jagada Thillainathan, Olga Vasilenko, Mingzhong Chen, Naga Chalamalasetty, Peifeng Chen, Bobby Boonyaratanakornkit, Robin Luedtke, Kristin Leach, Gabriel Arias, Michael Pratt, Krishana Gulla, Daniel B. Gowetski, Janel Holland-Linn, Leigh Anne Stephens, Paula Lei, Jessica Bahorich, Jonathan Cooper, Yanhong Yang, Eric Wang, William Shadrick
Abstract
The relative conservation of the influenza hemagglutinin (HA) stem compared to that of the immunodominant HA head makes the HA stem an attractive target for broadly protective influenza vaccines. Here we report the first-in-human, dose-escalation, open-label trial (NCT04579250) evaluating an unadjuvanted group 2 stabilized stem ferritin nanoparticle vaccine based on the H10 A/Jiangxi-Donghu/346/2013 influenza HA, H10ssF, in healthy adults. Participants received a single 20 mcg dose (n = 3) or two 60 mcg doses 16 weeks apart (n = 22). Vaccination with H10ssF was safe and well tolerated with only mild systemic and local reactogenicity reported. No serious adverse events occurred. Vaccination significantly increased homologous H10 HA stem binding and neutralizing antibodies at 2 weeks after both first and second vaccinations, and these responses remained above baseline at 40 weeks. Heterologous H3 and H7 binding antibodies also significantly increased after each vaccination and remained elevated throughout the study. These data indicate that the group 2 HA stem nanoparticle vaccine is safe and induces stem-directed binding and neutralizing antibodies.