An intranasal adjuvanted, recombinant influenza A/H5 vaccine primes against diverse H5N1 clades: a phase I trial

Meagan E. Deming, Franklin R. Toapanta, Marcela Pasetti, Hana Golding, Surender Khurana, Tarek Hamouda, Ali Fattom, Yuanyuan Liang, Sharon M. Tennant, Megan F. McGilvray, Paula J. Bernal, Jennifer J. Oshinsky, Shrimati Datta, Jasnehta Permala Booth, Lynda Coughlan, Kathleen M. Neuzil, Chad D. Costley, Karen L. Kotloff, Marcelo B. Sztein and Justin R. Ortiz ()
Additional contact information
Meagan E. Deming: University of Maryland School of Medicine
Franklin R. Toapanta: University of Maryland School of Medicine
Marcela Pasetti: University of Maryland School of Medicine
Hana Golding: US Food and Drug Administration
Surender Khurana: US Food and Drug Administration
Tarek Hamouda: BlueWillow Biologics, Inc.
Ali Fattom: BlueWillow Biologics, Inc.
Yuanyuan Liang: University of Maryland School of Medicine
Sharon M. Tennant: University of Maryland School of Medicine
Megan F. McGilvray: University of Maryland School of Medicine
Paula J. Bernal: University of Maryland School of Medicine
Jennifer J. Oshinsky: University of Maryland School of Medicine
Shrimati Datta: University of Maryland School of Medicine
Jasnehta Permala Booth: University of Maryland School of Medicine
Lynda Coughlan: University of Maryland School of Medicine
Kathleen M. Neuzil: University of Maryland School of Medicine
Chad D. Costley: BlueWillow Biologics, Inc.
Karen L. Kotloff: University of Maryland School of Medicine
Marcelo B. Sztein: University of Maryland School of Medicine
Justin R. Ortiz: University of Maryland School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract 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 (W805EC). 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

Date: 2025
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-64686-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64686-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-64686-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().