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Protective efficacy of the UniFluVec #influenza #vaccine vector against the highly pathogenic influenza A/Indonesia/5/2005 #H5N1 strain in #ferrets

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By G.M.

 


Highlights

• UniFluVec, an H1N1pdm vaccine candidate, includes NS1 and NEP modifications to boost attenuation and immunity.

• UniFluVec protects ferrets from H5N1, enhancing clearance, limiting lung damage, and ensuring 100 % survival after one dose.

• Replication-deficient UniFluVec shows cross-protection, supporting its potential as a pre-pandemic intranasal vaccine.


Abstract

Background

The emergence of new influenza strains with unpredictable antigenic properties poses a significant vaccination challenge. The increasing incidence of human H5 infections underscores the urgent need for effective pre-pandemic vaccines.

Methods

The UniFluVec and UniFluVec-wtNS1 viruses were designed as H1N1pdm vaccine candidates. Both viruses contained a heterologous A/Singapore/1/57-like (H2N2) NEP gene, which served as an attenuation factor. UniFluVec additionally carried a truncated to 124 amino acids NS1 gene, and an insertion of conserved influenza sequences. UniFluVec-wtNS1 retained the wild-type NS1 gene. The impact of NS1 and NEP modifications on attenuation and phenotypic markers was assessed in cells and mice. Safety and prophylactic efficacy were assessed in ferrets following a single intranasal immunisation with the maximum feasible dose (8.7 log10 EID50), followed by challenge with the highly pathogenic avian influenza virus (HPAIV) A/Indonesia/5/2005 (H5N1).

Results

Modifications in NS1 and NEP independently and synergistically induced a temperature-sensitive phenotype and enhanced type I/II interferon response, resulting in a highly attenuated vaccine profile. UniFluVec, incorporating both modifications within the NS genomic segment, demonstrated superior viral clearance, reducing lung damage, and ensuring 100 % survival in infected animals.

Conclusion

The replication-deficient UniFluVec vector demonstrates safety, immunogenicity, and protective efficacy against the heterologous HPAIV strain in ferrets following a single intranasal administration.

Source: Vaccine, https://www.sciencedirect.com/science/article/pii/S0264410X25010928?via%3Dihub

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