Safety and immunogenicity of a BPL-inactivated, whole-virus, universal influenza vaccine: a randomized, double-blinded, double-dummy, placebo-controlled, phase 1 clinical trial
12 affiliations
- 1Clinical Studies Unit, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD USA
- 2Translational Immunobiology Unit, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD USA
- 3Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD USA
- 4Viral Pathogenesis and Evolutions Section, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD USA
- 5Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD USA
- 6Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD USA
- 7Department of Veterinary Medicine, University of Maryland, College Park, MD USA
- 8Virginia-Maryland College of Veterinary Medicine, College Park, MD USA
- 9Biostatistics Research Branch, Office of Biostatistics Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD USA
- 10Laboratory of Translational Immunobiology, Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy
- 11Office of the Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD USA
- 12Office of the Director, National Institutes of Health, Bethesda, MD USA
Abstract
Influenza inflicts substantial burden of disease, but current vaccines have limited breadth of protection against strains and subtypes not in the vaccine. BPL-1357, a whole-virus, inactivated vaccine containing four wild-type, low-pathogenicity avian influenza viruses has demonstrated remarkable protection in animal models against a wide range of influenza viruses. In this phase I trial, forty-five healthy participants were randomized to receive BPL-1357 intramuscularly (IM), intranasally (IN), or placebo, in a prime and boost strategy, 28-days apart. The primary endpoints consisted of adverse events (AEs) and serious adverse events (SAEs) from enrollment through 28 days after the boost. The secondary endpoints were AEs and SAEs through 182 days after the boost and measurement of serum IgG and nasal IgA titers against hemagglutinin and neuraminidase vaccine antigens. Adverse effects were mostly mild and, other than mild injection-site pain more frequently observed in the IM group, occurred in a minority of patients. IM BPL-1357 induced higher serum IgG titers against H3, H5, and H7 relative to placebo, with 71.4%, 71.4%, and 85.7% of participants demonstrating a response. IM BPL-1357 vaccinated participants also experienced serum neutralizing and NA-specific responses, but no mucosal IgA responses against HA or NA. Subtle mucosal and serum responses were observed after IN vaccination, similar to preclinical experiments. These results suggest that BPL-1357 is well tolerated and immunogenic, particularly when given IM, but more work is needed to assess other dose levels, further characterize induced immunity, and evaluate efficacy against influenza infection and disease (NCT05027932).
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BibTeX
@article{giurgea2026safety,
title = {{Safety and immunogenicity of a BPL-inactivated, whole-virus, universal influenza vaccine: a randomized, double-blinded, double-dummy, placebo-controlled, phase 1 clinical trial}},
author = {Luca T. Giurgea and Alison Han and Lindsay M. Czajkowski and Holly Ann Baus and Gregory Mak and Matthias Lingemann and Ian Bellayr and Adriana Cervantes-Medina and Monica Gouzoulis and Kimberly Adao and Jenna Sherry and Rani Athota and Jackqueline Ardo and Robert Daniels and Viviane Callier and Jaekeun Park and Sally Hunsberger and Mattia Bonsignori and John H. Powers and John C. Kash and Jeffery K. Taubenberger and Matthew J. Memoli},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78583-w},
url = {https://doi.org/10.1038/s41467-026-78583-w},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Safety and immunogenicity of a BPL-inactivated, whole-virus, universal influenza vaccine: a randomized, double-blinded, double-dummy, placebo-controlled, phase 1 clinical trial
AU - Luca T. Giurgea
AU - Alison Han
AU - Lindsay M. Czajkowski
AU - Holly Ann Baus
AU - Gregory Mak
AU - Matthias Lingemann
AU - Ian Bellayr
AU - Adriana Cervantes-Medina
AU - Monica Gouzoulis
AU - Kimberly Adao
AU - Jenna Sherry
AU - Rani Athota
AU - Jackqueline Ardo
AU - Robert Daniels
AU - Viviane Callier
AU - Jaekeun Park
AU - Sally Hunsberger
AU - Mattia Bonsignori
AU - John H. Powers
AU - John C. Kash
AU - Jeffery K. Taubenberger
AU - Matthew J. Memoli
PY - 2026
DA - 2026/10/12
JO - Nature Communications
DO - 10.1038/s41467-026-78583-w
UR - https://doi.org/10.1038/s41467-026-78583-w
AB - Influenza inflicts substantial burden of disease, but current vaccines have limited breadth of protection against strains and subtypes not in the vaccine. BPL-1357, a whole-virus, inactivated vaccine containing four wild-type, low-pathogenicity avian influenza viruses has demonstrated remarkable protection in animal models against a wide range of influenza viruses. In this phase I trial, forty-five healthy participants were randomized to receive BPL-1357 intramuscularly (IM), intranasally (IN), or placebo, in a prime and boost strategy, 28-days apart. The primary endpoints consisted of adverse events (AEs) and serious adverse events (SAEs) from enrollment through 28 days after the boost. The secondary endpoints were AEs and SAEs through 182 days after the boost and measurement of serum IgG and nasal IgA titers against hemagglutinin and neuraminidase vaccine antigens. Adverse effects were mostly mild and, other than mild injection-site pain more frequently observed in the IM group, occurred in a minority of patients. IM BPL-1357 induced higher serum IgG titers against H3, H5, and H7 relative to placebo, with 71.4%, 71.4%, and 85.7% of participants demonstrating a response. IM BPL-1357 vaccinated participants also experienced serum neutralizing and NA-specific responses, but no mucosal IgA responses against HA or NA. Subtle mucosal and serum responses were observed after IN vaccination, similar to preclinical experiments. These results suggest that BPL-1357 is well tolerated and immunogenic, particularly when given IM, but more work is needed to assess other dose levels, further characterize induced immunity, and evaluate efficacy against influenza infection and disease (NCT05027932).
SN - 2041-1723
ER -