npj Vaccines (Sep 2024)
Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine
- Joseph P. Casazza,
- Amelia R. Hofstetter,
- Pamela J. M. 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 C. Burgos Florez,
- Ana M. Ortega-Villa,
- Preeti J. Apte,
- Larisa Strom,
- Lu Wang,
- Marjaan Imam,
- Manjula Basappa,
- Mursal Naisan,
- Mike Castro,
- Jessica F. Trost,
- Sandeep R. Narpala,
- Hillary A. Vanderven,
- Galina V. Yamshchikov,
- Nina M. Berkowitz,
- Ingelise J. Gordon,
- Sarah H. Plummer,
- Diane L. Wycuff,
- Sandra Vazquez,
- Rebecca A. Gillespie,
- Adrian Creanga,
- William C. Adams,
- Kevin Carlton,
- Jason G. Gall,
- Adrian B. McDermott,
- Leonid A. 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 K. Dropulic,
- The VRC 323 study team
Affiliations
- Joseph P. Casazza
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Amelia R. Hofstetter
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Pamela J. M. Costner
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- LaSonji A. Holman
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Cynthia S. Hendel
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Alicia T. Widge
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Richard L. Wu
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- William R. Whalen
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Jennifer Cunningham
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Anita Arthur
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Xiaolin Wang
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Abidemi Ola
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Jamie Saunders
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Floreliz Mendoza
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Laura Novik
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Maria C. Burgos Florez
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Ana M. Ortega-Villa
- Biostatistics Research Branch, Division of Clinical Research, National Institutes of Health
- Preeti J. Apte
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Larisa Strom
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Lu Wang
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Marjaan Imam
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Manjula Basappa
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Mursal Naisan
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Mike Castro
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Jessica F. Trost
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Sandeep R. Narpala
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Hillary A. Vanderven
- Australian Institute of Tropical Health and Medicine, James Cook University
- Galina V. Yamshchikov
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Nina M. Berkowitz
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Ingelise J. Gordon
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Sarah H. Plummer
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Diane L. Wycuff
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Sandra Vazquez
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Rebecca A. Gillespie
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Adrian Creanga
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- William C. Adams
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Kevin Carlton
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Jason G. Gall
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Adrian B. McDermott
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Leonid A. Serebryannyy
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Katherine V. Houser
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Richard A. Koup
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Barney S. Graham
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Julie E. Ledgerwood
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- John R. Mascola
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Theodore C. Pierson
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Sarah F. Andrews
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Masaru Kanekiyo
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Lesia K. Dropulic
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health
- The VRC 323 study team
- DOI
- https://doi.org/10.1038/s41541-024-00959-0
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 10
Abstract
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.
