ArticleJournal of virology2025
Live-attenuated influenza virus vaccine strain with an engineered temperature-sensitive and genetically stable viral polymerase variant.
Article in Journal of virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- PB1 mutations as key drivers of influenza A virus evolution.Frontiers in microbiology · 2026Review
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Authors and funding
8 authors.
Funding
Abstract
Vaccination against seasonal influenza is considered an effective means of reducing morbidity and mortality. Live-attenuated vaccines offer more protection against influenza than inactivated vaccines as they efficiently induce cellular immunity and provide cross-immunogenicity against various antigenic subtypes. For the production of safer live-attenuated vaccines, it is important to develop a common master donor vaccine strain in which pathogenic revertants are much less likely to appear. In this study, we introduced a single amino acid substitution of Lys471 into the PB1 polymerase subunit of influenza A virus and succeeded in isolating an attenuated mutant virus that exhibits a temperature-sensitive phenotype. The Lys471 residue is located in the polymerase motif D on PB1 and is positioned near the entrance tunnel domain for incoming nucleotide triphosphate. Although 10 viable PB1-Lys471 mutants did not proliferate at 37°C, their variants could replicate at 31°C and 34°C. Moreover, we found that PB1-Lys471Pro variant induces a genetically stable influenza virus phenotype; this mutant virus did not revert to wild-type phenotype from the temperature-sensitive phenotype by serial virus passages. Animal experiments have demonstrated that these PB1 mutant strains work effectively as live-attenuated vaccines. Application of the PB1-Lys471 substitution to a master donor strain is expected to lead to the development of a safer, high-performance, and widely used live-attenuated vaccine with the antigen of circulating influenza viruses. IMPORTANCE: Influenza virus elicits respiratory tract disease and is a threat to global human health. Vaccination is considered an effective tool for reducing the morbidity and mortality caused by influenza disease. The only licensed live-attenuated influenza vaccine that has been proven safe and effective is FluMist. In this study, we isolated an attenuated influenza mutant virus with a Lys471 single amino acid substitution in PB1, which displayed a temperature-sensitive and a low-pathogenicity phenotype. By applying the PB1-Lys471 substitution to the vaccine mother strain or the circulating influenza virus using reverse genetic technology, a high-performance and safe live-attenuated vaccine carrying the viral antigens of the vaccine-targeted strain can be developed.
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