tetano
Editor, Senior Moderator
Vaccine
. 2026 Jul 23:88:128962.
doi: 10.1016/j.vaccine.2026.128962. Online ahead of print.
Lung-resident T-cell immunity dominates protection induced by an intranasal adenoviral nucleoprotein influenza vaccine
Wen-Chien Wang[SUP] 1 [/SUP], Marwa Alhashimi[SUP] 2 [/SUP], Vivek Gairola[SUP] 1 [/SUP], Muralimanohara S T Murala[SUP] 1 [/SUP], Shaurya Dumka[SUP] 1 [/SUP], Ekramy E Sayedahmed[SUP] 1 [/SUP], Suryaprakash Sambhara[SUP] 3 [/SUP], Suresh K Mittal[SUP] 4 [/SUP]
Affiliations
Frequent antigenic drift in influenza viruses necessitates broadly protective vaccines. This study evaluated an intranasal adenoviral-vector vaccine expressing influenza A nucleoprotein (NP) fused to the autophagy-inducing peptide C5. A heterologous prime-boost regimen using chimpanzee and bovine adenoviral platforms induced strong NP-specific humoral and cellular immune responses in mice. High serum and lung IgG/IgA level were detected, accompanied by enhanced antibody-dependent cellular cytotoxicity. Cellular analyses revealed potent NP-specific cytokine responses and expansion of effector memory (T[SUB]EM[/SUB]) and tissue-resident memory (T[SUB]RM[/SUB]) T cells, particularly CD8[SUP]+[/SUP] T[SUB]RM[/SUB], in the lungs. Experiments using immune-deficient mice showed that B cells and CD8[SUP]+[/SUP] T cells independently contributed to early viral clearance. Adoptive transfer studies demonstrated that lung-derived T cells conferred the strongest heterosubtypic viral restriction, whereas systemic T cells and antibodies provided partial protection. Together, these findings highlight the critical role of lung-resident T cells in cross-protective viral control, supporting intranasal NP-based adenoviral vaccines as promising universal influenza vaccine candidates.
Keywords: Adoptive transfer; Bovine adenoviral vector; Broadly protective influenza vaccine; Knockout mouse studies; Nucleoprotein; Tissue-resident memory T cell.
. 2026 Jul 23:88:128962.
doi: 10.1016/j.vaccine.2026.128962. Online ahead of print.
Lung-resident T-cell immunity dominates protection induced by an intranasal adenoviral nucleoprotein influenza vaccine
Wen-Chien Wang[SUP] 1 [/SUP], Marwa Alhashimi[SUP] 2 [/SUP], Vivek Gairola[SUP] 1 [/SUP], Muralimanohara S T Murala[SUP] 1 [/SUP], Shaurya Dumka[SUP] 1 [/SUP], Ekramy E Sayedahmed[SUP] 1 [/SUP], Suryaprakash Sambhara[SUP] 3 [/SUP], Suresh K Mittal[SUP] 4 [/SUP]
Affiliations
- PMID: 42492242
- DOI: 10.1016/j.vaccine.2026.128962
Frequent antigenic drift in influenza viruses necessitates broadly protective vaccines. This study evaluated an intranasal adenoviral-vector vaccine expressing influenza A nucleoprotein (NP) fused to the autophagy-inducing peptide C5. A heterologous prime-boost regimen using chimpanzee and bovine adenoviral platforms induced strong NP-specific humoral and cellular immune responses in mice. High serum and lung IgG/IgA level were detected, accompanied by enhanced antibody-dependent cellular cytotoxicity. Cellular analyses revealed potent NP-specific cytokine responses and expansion of effector memory (T[SUB]EM[/SUB]) and tissue-resident memory (T[SUB]RM[/SUB]) T cells, particularly CD8[SUP]+[/SUP] T[SUB]RM[/SUB], in the lungs. Experiments using immune-deficient mice showed that B cells and CD8[SUP]+[/SUP] T cells independently contributed to early viral clearance. Adoptive transfer studies demonstrated that lung-derived T cells conferred the strongest heterosubtypic viral restriction, whereas systemic T cells and antibodies provided partial protection. Together, these findings highlight the critical role of lung-resident T cells in cross-protective viral control, supporting intranasal NP-based adenoviral vaccines as promising universal influenza vaccine candidates.
Keywords: Adoptive transfer; Bovine adenoviral vector; Broadly protective influenza vaccine; Knockout mouse studies; Nucleoprotein; Tissue-resident memory T cell.