1. Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine.
- Author
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Casazza JP, Hofstetter AR, Costner PJM, Holman LA, Hendel CS, Widge AT, Wu RL, Whalen WR, Cunningham J, Arthur A, Wang X, Ola A, Saunders J, Mendoza F, Novik L, Burgos Florez MC, Ortega-Villa AM, Apte PJ, Strom L, Wang L, Imam M, Basappa M, Naisan M, Castro M, Trost JF, Narpala SR, Vanderven HA, Yamshchikov GV, Berkowitz NM, Gordon IJ, Plummer SH, Wycuff DL, Vazquez S, Gillespie RA, Creanga A, Adams WC, Carlton K, Gall JG, McDermott AB, Serebryannyy LA, Houser KV, Koup RA, Graham BS, Ledgerwood JE, Mascola JR, Pierson TC, Andrews SF, Kanekiyo M, and Dropulic LK
- 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., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
- Published
- 2024
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