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Peer reviewedOpen accessInfluenza

Intranasal delivery of a COBRA-based protein vaccine adjuvanted with c-di-AMP enhances breadth of protective immune responses against seasonal influenza viruses

Frontiers in Immunology·

Camila C. S. Caetano, David A. Prots, Matthew H. Thomas, Dylan R. Micallef, Robert A. Richardson, Ted M. Ross

DOI
10.3389/fimmu.2026.1876199
PMID
PMCID
OpenAlex
Study type
Journal article
Publisher
Frontiers Media SA
Article type
journal-article
Integrity
current

Why this research matters now

The findings provide preclinical evidence that a mucosally delivered vaccine strategy targeting multiple influenza antigens may be relevant to research on protection against antigenically drifted seasonal influenza strains. The evidence is limited to mouse immunogenicity and challenge outcomes and does not establish effectiveness in humans.

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Structured evidence summary

Research question

The study examined whether an intranasal multivalent vaccine using computationally optimized influenza HA and NA antigens, with c-di-AMP adjuvant, could generate broad immune responses and protection against influenza A and B strains in mice.

Study design

This was a controlled preclinical vaccination and viral-challenge study in mice. Immunologically naive and pre-immune animals received pentavalent formulations with different antigen doses and adjuvant conditions, followed by assessment of immune responses and outcomes after influenza challenge.

Population and setting

The study used naive and pre-immune DBA/2J mice. Animals were immunized intranasally and challenged with influenza A H1N1, influenza A H3N2, or influenza B viruses.

Main findings

The adjuvanted COBRA HA/NA formulations produced strong antibody and cellular immune responses in the mouse models, including dose-related IgG and HAI responses. After lethal viral challenge, vaccinated mice had less weight loss, lower lung viral titres, and better survival, with the clearest protection in groups receiving c-di-AMP.

Public-health relevance

The findings provide preclinical evidence that a mucosally delivered vaccine strategy targeting multiple influenza antigens may be relevant to research on protection against antigenically drifted seasonal influenza strains. The evidence is limited to mouse immunogenicity and challenge outcomes and does not establish effectiveness in humans.

Important limitations

The evidence comes from DBA/2J mouse experiments with controlled viral challenge, so its applicability beyond this model is not established by the supplied material. The summary also relies on the supplied single-article abstract and metadata; the original paper is required for decision-grade assessment of methods, analyses, and limitations.

GIDS interpretation

The article is discoverable as influenza vaccination research and provides context on a preclinical mucosal vaccine approach involving broadly reactive antigens and an adjuvant. The supplied evidence does not connect these experimental findings to any live surveillance signal.

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Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

03

Evidence relationships

This article has 6 auditable classifier relationships to diseases, places, topics, and study design.

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