Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine

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.

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Publication Details

Journal
npj Vaccines
Published
2024-09-17
DOI
https://doi.org/10.1038/s41541-024-00959-0
Citations
17
Primary Topic
Monoclonal and Polyclonal Antibodies Research
Type
article
Field-Weighted Citation Impact
6.87

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article

Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine

Adrian B. McDermott, Anita Arthur, Nina M. Berkowitz, Abidemi Ola et al.
17 citations
npj Vaccines
Monoclonal and Polyclonal Antibodies Research
6.87
article

Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine

Adrian B. McDermott, Anita Arthur, Nina M. Berkowitz, Abidemi Ola, Pamela Costner, William R Whalen, Jennifer Cunningham, Richard A. Koup, Barney S. Graham, Alicia T. Widge, Lesia Dropulic, Preeti Apte, Manjula Basappa, Laura Novik, Diane Wycuff, Sandra Vazquez, Galina V. Yamshchikov, Sarah F. Andrews, Theodore C. Pierson, Adrian Creanga, Joseph P. Casazza, Masaru Kanekiyo, Hillary A. Vanderven, Mike Castro, Jamie Saunders, Ingelise J. Gordon, Sandeep Narpala, Marjaan Imam, Leonid Serebryannyy, John R. Mascola, Katherine V. Houser, Rebecca A. Gillespie, Amelia R. Hofstetter, Jason G. Gall, Maria Claudia Burgos Florez, Cynthia S. Hendel, Ana Maria Ortega‐Villa, Mursal Naisan, Lu Wang, Xiaolin Wang, William C. Adams, Richard L Wu, Larisa Strom, Jessica F Trost, Kevin Carlton, Julie E Ledgerwood, LaSonji A Holman, Floreliz Mendoza, Sarah H. Plummer
article en
17 citations

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.

npj VaccinesVol. 9(1)
Australian Institute of Tropical Health and Medicine (AU), United States Public Health Service (US), United States Public Health Service Commissioned Officers Association (US), National Institute of Allergy and Infectious Diseases (US), National Institutes of Health Clinical Center (US), James Cook University (AU)
Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Burnet Institute, James Cook University, National Institutes of Health, National Institute of Allergy and Infectious Diseases
Life in Land
Openalex Percentile: Top 2%
Monoclonal and Polyclonal Antibodies Research
6.87
DOIOpen Access PDFOpenAlex
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