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.

Details

Title
Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine
Author
Casazza, Joseph P. 1   VIAFID ORCID Logo  ; Hofstetter, Amelia R. 1   VIAFID ORCID Logo  ; Costner, Pamela J. M. 1 ; Holman, LaSonji A. 1 ; Hendel, Cynthia S. 1 ; Widge, Alicia T. 1 ; Wu, Richard L. 2   VIAFID ORCID Logo  ; Whalen, William R. 1 ; Cunningham, Jennifer 1 ; Arthur, Anita 1 ; Wang, Xiaolin 1 ; Ola, Abidemi 1 ; Saunders, Jamie 1 ; Mendoza, Floreliz 1 ; Novik, Laura 1 ; Burgos Florez, Maria C. 1 ; Ortega-Villa, Ana M. 3 ; Apte, Preeti J. 1 ; Strom, Larisa 1 ; Wang, Lu 1 ; Imam, Marjaan 1 ; Basappa, Manjula 1 ; Naisan, Mursal 1 ; Castro, Mike 1   VIAFID ORCID Logo  ; Trost, Jessica F. 1   VIAFID ORCID Logo  ; Narpala, Sandeep R. 1 ; Vanderven, Hillary A. 4 ; Yamshchikov, Galina V. 1 ; Berkowitz, Nina M. 1 ; Gordon, Ingelise J. 1 ; Plummer, Sarah H. 1 ; Wycuff, Diane L. 1 ; Vazquez, Sandra 1 ; Gillespie, Rebecca A. 1 ; Creanga, Adrian 1 ; Adams, William C. 1 ; Carlton, Kevin 1 ; Gall, Jason G. 1   VIAFID ORCID Logo  ; McDermott, Adrian B. 1   VIAFID ORCID Logo  ; Serebryannyy, Leonid A. 1 ; Houser, Katherine V. 1   VIAFID ORCID Logo  ; Koup, Richard A. 1 ; Graham, Barney S. 1 ; Ledgerwood, Julie E. 1 ; Mascola, John R. 1 ; Pierson, Theodore C. 1 ; Andrews, Sarah F. 1   VIAFID ORCID Logo  ; Kanekiyo, Masaru 1   VIAFID ORCID Logo  ; Dropulic, Lesia K. 1   VIAFID ORCID Logo  ; Abrah, Akuah 1 ; Awan, Seemal F. 1 ; Amoa-Awua, Obrimpong 1 ; Apgar, Martin 1 ; Beck, Allison 1 ; Brooks, Katherine 1 ; Bruington, Tommy 1 ; Burch, Eugenia 1 ; Case, Chris 1 ; Coates, Emily E. 1 ; Coe, Erykah 1 ; Eshun, Aba M. 1 ; Gaudinski, Martin R. 1 ; Dyer, Renunda 1 ; Le, Lam 1 ; Larkin, Brenda 1 ; Misasi, John 1 ; Morgan, Patricia 1 ; Mueller, Allen 1 ; Nguyen, Thuy 1 ; O’Callahan, Mark 1 ; Ourahmane, Amine 1 ; Parker, Karen M. 1 ; Pittman, Iris 1 ; Reiber, Matthew 1 ; Requilman, LaShawn 1 ; Shimberg, Geoffrey 1 ; Silva, Rosa 1 ; Stein, Judy 1 ; Telscher, Shinyi 1 ; Thillainathan, Jagada 1 ; Vasilenko, Olga 1 ; Chen, Mingzhong 1 ; Chalamalasetty, Naga 1 ; Chen, Peifeng 1 ; Boonyaratanakornkit, Bobby 1 ; Luedtke, Robin 1 ; Leach, Kristin 1 ; Arias, Gabriel 1 ; Pratt, Michael 1 ; Gulla, Krishana 1 ; Gowetski, Daniel B. 1 ; Holland-Linn, Janel 1 ; Stephens, Leigh Anne 1 ; Lei, Paula 1 ; Bahorich, Jessica 1 ; Cooper, Jonathan 1 ; Yang, Yanhong 1 ; Wang, Eric 1 ; Shadrick, William 1 ; Kueltzo, Lisa 1 ; Banappagari, Sashikanth 1 ; Albright, Gabriela 1 ; Dobrescu, Gelu 1 ; Nugent, Sean 1 ; Moxey, Gabriel 1 ; Chaudhuri, Rajoshi 1 

1  National Institutes of Health, Vaccine Research Center, National Institute of Allergy and Infectious Disease, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
2  National Institutes of Health, Vaccine Research Center, National Institute of Allergy and Infectious Disease, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); U.S. Public Health Service Commissioned Corps, Rockville, USA (GRID:grid.417684.8) (ISNI:0000 0001 1554 5300) 
3  National Institutes of Health, Biostatistics Research Branch, Division of Clinical Research, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
4  James Cook University, Australian Institute of Tropical Health and Medicine, Douglas, Australia (GRID:grid.1011.1) (ISNI:0000 0004 0474 1797) 
Pages
171
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20590105
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41541-024-00959-0
ProQuest document ID
3106223626
Copyright
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.