Journal Article

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

Pleimes, Dirk, Krokhin, Artem, Egorov, Andrej, Romanova, Julia, Ferko, Boris, Vareckova, Eva, Kostolansky, Frantisek

2025

Overview

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

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Administration, Intranasal / Allergy and Immunology / Amino acids / Animals / Antibodies, Viral - blood / Attenuation / Avian flu / Avian influenza / Challenge model / Effectiveness / Epidemics / Fatalities / Female / Ferrets / genes / Genetic Vectors / genomics / humans / Immunization / Immunogenicity / Infections / Influenza / Influenza A / Influenza A virus / Influenza A Virus, H1N1 Subtype - genetics / Influenza A Virus, H1N1 Subtype - immunology / Influenza A Virus, H5N1 Subtype - genetics / Influenza A Virus, H5N1 Subtype - immunology / Influenza A Virus, H5N1 Subtype - pathogenicity / influenza vaccines / Influenza Vaccines - administration & dosage / Influenza Vaccines - genetics / Influenza Vaccines - immunology / interferons / Intranasal administration / Live influenza vaccine / live vaccines / lungs / Mice / Mice, Inbred BALB C / Mustela / Nep gene / NS1 protein / Orthomyxoviridae Infections - immunology / Orthomyxoviridae Infections - prevention & control / Pandemics / phenotype / Phenotypes / Plasmids / Proteins / Replication-deficient virus / UniFluVec vector / vaccination / Vaccine Efficacy / Vaccines / Vaccines, Attenuated - administration & dosage / Vaccines, Attenuated - genetics / Vaccines, Attenuated - immunology / Viral Nonstructural Proteins - genetics / Viral Nonstructural Proteins - immunology / Viruses