biostudies-literatureUnknownGe CNational Natural Science Foundation of ChinaVaccination is considered one of the most effective methods for preventing avian influenza. The influenza neuraminidase (NA) enzyme is a promising candidate for a conserved influenza vaccine, offering long-term and effective cross-protection against the disease. The aim of this study is to develop a <i>Salmonella</i>-vectored vaccine with strong protective efficacy against H9N2 avian influenza virus. We utilized the antibiotic-free balanced-lethal system of regulated delayed-lysis <i>Salmonella</i> (χ11218) as the starting strain to construct a <i>focA</i> gene-deleted <i>Salmonella</i> (χYL57) strain. To optimize the vaccine design, we fused a tetravalent NA protein (tetramer-NA) with a chicken dendritic cell-targeting peptide (chDCpep) and delivered it via χ11218 or χYL57, yielding the cMicrobiology spectrume0142125https://www.ebi.ac.uk/biostudies/studies/S-EPMC12671097biostudies-literatureProtection against H9N2 challenge in chickens via &lt;i&gt;Salmonella&lt;/i&gt; with a &lt;i&gt;focA&lt;/i&gt; mutation delivered by a dendritic cell-targeted avian influenza virus NA protein tetramer.PMC1267109732072897Ge CZhang GWang CHuang HJia FSun YGuo QWang MJiang YZhang THe YZhang YTian YGao YWang WYang TGong JWang ZfalseProtection against H9N2 challenge in chickens via &lt;i&gt;Salmonella&lt;/i&gt; with a &lt;i&gt;focA&lt;/i&gt; mutation delivered by a dendritic cell-targeted avian influenza virus NA protein tetramer.Vaccination is considered one of the most effective methods for preventing avian influenza. The influenza neuraminidase (NA) enzyme is a promising candidate for a conserved influenza vaccine, offering long-term and effective cross-protection against the disease. The aim of this study is to develop a <i>Salmonella</i>-vectored vaccine with strong protective efficacy against H9N2 avian influenza virus. We utilized the antibiotic-free balanced-lethal system of regulated delayed-lysis <i>Salmonella</i> (χ11218) as the starting strain to construct a <i>focA</i> gene-deleted <i>Salmonella</i> (χYL57) strain. To optimize the vaccine design, we fused a tetravalent NA protein (tetramer-NA) with a chicken dendritic cell-targeting peptide (chDCpep) and delivered it via χ11218 or χYL57, yielding the c2025-01-01T00:00:00Z2025 Oct2026-06-05T22:05:55.998Z2026-05-22T03:15:41.99ZS-EPMC126710974114340510.1128/spectrum.01421-25