ArticleVirology journal2025
Intranasally administered whole virion inactivated vaccine against clade 2.3.4.4b H5N1 influenza virus with optimized antigen and increased cross-protection.
Article in Virology journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed.
- Article
- Evolution of H5N1 Cross-Species Transmission: Adaptive Mutations Driving Avian-to-Human Infection.Advanced genetics (Hoboken, N.J.) · 2026Article
- Baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating lethal influenza A(H5N1) HA clade 2.3.4.4b infection in mice.Nature communications · 2026Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
The global spread, frequent antigenic changes, and pandemic potential of clade 2.3.4.4b highly pathogenic avian influenza H5N1 underscore the urgent need for robust cross-protective vaccines. Here, we developed a clade 2.3.4.4b H5N1 whole inactivated virus (WIV) vaccine strain with improved structural stability, productivity, and safety. By analyzing the evolutionary trends of clade 2.3.4.4b H5N1 viruses, we identified a key mutation (R90K) that increases heat stability while preserving antigenicity. Additionally, the PB2 gene of PR8 was replaced with a prototypical avian PB2 gene to increase replication efficiency in embryonated chicken eggs and reduce replication efficiency in mammalian cells, thereby improving productivity and biosafety. We found that our optimized clade 2.3.4.4b H5N1 vaccine strain (22W_KY), inactivated with binary ethylenimine (BEI), had superior antigen internalization into respiratory epithelial cells compared to those inactivated with formaldehyde or beta-propiolactone. Following intranasal administration to mice, the BEI-inactivated 22W_KY also elicited significantly stronger systemic IgG, mucosal IgA, and T-cell responses, especially in the lungs. Protective efficacy studies revealed that the BEI-inactivated 22W_KY vaccine provided complete protection against heterologous viral challenges and significant protection against heterosubtypic viral challenges, with no weight loss and complete suppression of the viral load in the respiratory tract in 2 of 3 mice. These results indicate that the BEI-inactivated 22W_KY vaccine could serve as a promising candidate for a safe, stable, cost-efficient, and broadly protective intranasal influenza vaccine against zoonotic and pandemic threats.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.