An intranasal adjuvanted, recombinant influenza A/H5 vaccine primes against diverse H5N1 clades: a phase I trial
Mucosal influenza vaccines may provide improved protection against infection and transmission, but their development is hindered by absence of immune correlates of protection. Here, we report a randomized, controlled phase I trial of a recombinant influenza A/H5 (A/Indonesia/05/2005, clade 2.1) hemagglutinin vaccine formulated with a nanoemulsion adjuvant (W<sub>80</sub>5EC). The vaccine is administered intranasally in two doses 28 days apart at three antigen levels. Controls receive unadjuvanted H5 or placebo. Six months later, participants receive an intramuscular boost with unadjuvanted inactivated A/H5N1 (A/Vietnam/1203/2004, clade 1) vaccine. Primary outcomes are solicited and unsolicited adverse events (AEs), laboratory safety abnormalities, medically-attended AEs, potential immune-mediated conditions, new-onset chronic conditions, and serious AEs. All vaccines are well tolerated. After the intranasal series, hemagglutination inhibition and microneutralization responses are minimal. However, adjuvanted H5 recipients show significant increases in mucosal and serum IgG/IgA, surface plasmon resonance antibody binding, memory B and CD4 T cell activity, and antibody-dependent cell-mediated cytotoxicity. Following H5N1 boost, participants mount robust responses across measurements and have microneutralization responses against diverse H5N1 clades (including circulating clade 2.3.4.4b). Findings demonstrate successful mucosal priming and broad cross-clade responses. This intranasal vaccine supports further exploration of mucosal immune biomarkers and may accelerate development of intranasal influenza vaccines. ClinicalTrials.gov registration: NCT05397119.
Authors
- James C. Booth (ORCID: https://orcid.org/0000-0002-0256-653X)
- Justin R. Ortiz (ORCID: https://orcid.org/0000-0002-3138-5965)
- Jingping Hu (ORCID: https://orcid.org/0000-0001-5548-1241)
- Tarek Hamouda
- Chad D. Costley
- Marcelo B. Sztein (ORCID: https://orcid.org/0000-0001-8282-860X)
- James Campbell (ORCID: https://orcid.org/0000-0002-2294-2547)
- Hugo Acosta
- Karen L. Kotloff (ORCID: https://orcid.org/0000-0003-1808-6431)
- Olivia Posadas
- Rekha R. Rapaka (ORCID: https://orcid.org/0000-0002-4770-4422)
- Joseph Nkeze
- Kathleen M. Neuzil (ORCID: https://orcid.org/0000-0001-9480-2714)
- Ifayet P. L. Johnson-Mayo
- Jody Manischewitz
- Meagan E. Deming (ORCID: https://orcid.org/0000-0003-2574-0542)
- Surender Khurana (ORCID: https://orcid.org/0000-0002-0593-7965)
- Jennifer Oshinsky (ORCID: https://orcid.org/0000-0002-6919-6780)
- Franklin R. Toapanta (ORCID: https://orcid.org/0000-0001-9439-0828)
- Shrimati Datta
- Paula J. Bernal
- Hana Golding
- Marcela F. Pasetti (ORCID: https://orcid.org/0000-0003-0894-4009)
- Insung Kang
- Vaidehi Agrawal (ORCID: https://orcid.org/0000-0002-1958-630X)
- Lynda Coughlan (ORCID: https://orcid.org/0000-0001-9880-6560)
- Yuanyuan Liang (ORCID: https://orcid.org/0000-0003-0360-286X)
- Ashish Mishra (ORCID: https://orcid.org/0000-0003-0959-5007)
- Cosette G. Schneider (ORCID: https://orcid.org/0000-0001-5825-7640)
- Sharon M. Tennant
- Douglas M. Smith
- Ali Fattom
- Lisa R. King
- Megan F. McGilvray
Institutions
- University of Maryland, Baltimore (US)
- Center for Biologics Evaluation and Research (US)
- Cell Biologics (United States) (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-06
- DOI
- https://doi.org/10.1038/s41467-025-64686-3
- Citations
- 1
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 1.35
Funders
- U.S. Department of Health and Human Services
- Sanofi
- National Institutes of Health
- Biomedical Advanced Research and Development Authority
- National Institute of Allergy and Infectious Diseases