AI Article Synopsis

  • Live attenuated influenza vaccines provide broader and longer-lasting protection than inactivated vaccines, making them a valuable option for combating the virus.
  • Researchers synthesized a modified neuraminidase (NA) gene to explore its potential for creating an attenuated virus but found that it needed some wild-type sequences to be successfully packaged.
  • The resulting vaccine candidate, called 20/13repNA, showed a significantly lower toxicity in mice and effectively induced a strong immune response, demonstrating the promise of this approach for developing more effective flu vaccines.

Article Abstract

Live attenuated influenza vaccines offer broader and longer-lasting protection in comparison to inactivated influenza vaccines. The neuraminidase (NA) surface glycoprotein of influenza A virus is essential for the release and spread of progeny viral particles from infected cells. In this study, we de novo synthesized the NA gene, in which 62% of codons were synonymously changed based on mammalian codon bias usage. The codon-reprogrammed NA (repNA) gene failed to be packaged into the viral genome, which was achievable with partial restoration of wild-type NA sequence nucleotides at the 3' and 5' termini. Among a series of rescued recombinant viruses, we selected 20/13repNA, which contained 20 and 13 nucleotides of wild-type NA at the 3' and 5' termini of repNA, respectively, and evaluated its potential as a live attenuated influenza vaccine. The 20/13repNA is highly attenuated in mice, and the calculated LD was about 10,000-fold higher than that of the wild-type (WT) virus. Intranasal inoculation of the 20/13repNA virus in mice induced viral-specific humoral, cell-mediated, and mucosal immune responses. Mice vaccinated with the 20/13repNA virus were protected from the lethal challenge of both homologous and heterologous viruses. This strategy may provide a new method for the development of live, attenuated influenza vaccines for a better and more rapid response to influenza threats.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9959331PMC
http://dx.doi.org/10.3390/vaccines11020391DOI Listing

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