Influenza Virus Carrying a Codon-Reprogrammed Neuraminidase Gene as a Strategy for Live Attenuated Vaccine

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Live attenuated influenza vaccines (LAIVs) provide broader, longer-lasting immunity than inactivated vaccines.
• Neuraminidase (NA) is crucial for influenza A virus replication and spread.

Purpose of the Study:

• To engineer a novel live attenuated influenza vaccine by reprogramming the NA gene.
• To evaluate the immunogenicity and protective efficacy of the engineered vaccine.

Main Methods:

• De novo synthesis of the NA gene with codon bias reprogramming (repNA).
• Rescue of recombinant viruses with partial restoration of wild-type NA termini (20/13repNA).
• Assessment of attenuation, immunogenicity, and protective efficacy in a mouse model.

Main Results:

• The codon-reprogrammed NA gene (repNA) required partial wild-type sequence restoration for viral packaging.
• The 20/13repNA virus exhibited high attenuation in mice (LD50 ~10,000-fold higher than WT).
• Intranasal inoculation induced robust humoral, cell-mediated, and mucosal immune responses, conferring protection against homologous and heterologous viral challenges.

Conclusions:

• Codon reprogramming of the NA gene is a viable strategy for developing live attenuated influenza vaccines.
• The 20/13repNA vaccine candidate shows significant potential for broad influenza A virus protection.
• This approach offers a new avenue for rapid development of influenza vaccines against emerging threats.