tetano
Editor, Senior Moderator
Antiviral Res
. 2025 Sep 25:106284.
doi: 10.1016/j.antiviral.2025.106284. Online ahead of print. Intranasal Vaccine Induces Broad and Long-Lasting Immunity Against the Hemagglutinin Stem of Group 2 Influenza A Viruses
Wanyue Zhang[SUP] 1 [/SUP], Jérémie Prévost[SUP] 2 [/SUP], Angela Sloan[SUP] 2 [/SUP], Levi Tamming[SUP] 1 [/SUP], Annabelle Pfeifle[SUP] 1 [/SUP], Caroline Gravel[SUP] 3 [/SUP], Sathya N Thulasi Raman[SUP] 3 [/SUP], Gary Van Domselaar[SUP] 2 [/SUP], Michael J W Johnston[SUP] 4 [/SUP], Lisheng Wang[SUP] 5 [/SUP], Simon Sauve[SUP] 3 [/SUP], Michael Rosu-Myles[SUP] 1 [/SUP], Darwyn Kobasa[SUP] 2 [/SUP], Anh Tran[SUP] 6 [/SUP], Wangxue Chen[SUP] 7 [/SUP], Xu Zhang[SUP] 3 [/SUP], David Safronetz[SUP] 8 [/SUP], Xuguang Li[SUP] 9 [/SUP]
Affiliations
Influenza A viruses are categorized into two phylogenetic groups (group 1 and group 2) based on the structure of their hemagglutinin (HA) protein. Within group 2, H3N2 poses a particular challenge due to its rapid evolution, limited vaccine efficacy, and association with more severe influenza seasons. Although T cell responses have been extensively studied in the context of vaccine-induced protection, HA stem (HA2)-specific T cell responses have been relatively understudied, especially those related to nasal immunity. To address this, we engineered an adenoviral vector vaccine (Ad-HA2) expressing a consensus hemagglutinin stem sequence, derived through bioinformatic analysis of all H3 strains. The vaccine conferred heterosubtypic protection against lethal challenges with either H3N2 or H7N9, both belonging to group 2 influenza A viruses, with protection lasting at least six months post-vaccination. Notably, the vaccine induced robust HA2-specific humoral and cell-mediated responses in the nasal-associated lymphoid tissue (NALT) of the upper respiratory tract, the first line of immune defense against inhaled pathogens. The vaccine also elicited significant levels of antibodies and T cell responses in the lower respiratory tract and pulmonary immune sites. Furthermore, circulating antibodies in the serum demonstrated effective antibody-dependent cellular cytotoxicity (ADCC) activity. Finally, using a peptide pool matrix screening approach combined with in silico verification, we identified an immunogenic C-terminus region of the HA2 consensus sequence that activated CD4+ and CD8+ T cells, which warrants further investigation. Collectively, these findings are informative for the design and evaluation of mucosal influenza vaccines targeting the hemagglutinin stem.
Keywords: H3N2; H5N1; T cell; hemagglutinin stem; influenza; mucosal vaccine.
. 2025 Sep 25:106284.
doi: 10.1016/j.antiviral.2025.106284. Online ahead of print. Intranasal Vaccine Induces Broad and Long-Lasting Immunity Against the Hemagglutinin Stem of Group 2 Influenza A Viruses
Wanyue Zhang[SUP] 1 [/SUP], Jérémie Prévost[SUP] 2 [/SUP], Angela Sloan[SUP] 2 [/SUP], Levi Tamming[SUP] 1 [/SUP], Annabelle Pfeifle[SUP] 1 [/SUP], Caroline Gravel[SUP] 3 [/SUP], Sathya N Thulasi Raman[SUP] 3 [/SUP], Gary Van Domselaar[SUP] 2 [/SUP], Michael J W Johnston[SUP] 4 [/SUP], Lisheng Wang[SUP] 5 [/SUP], Simon Sauve[SUP] 3 [/SUP], Michael Rosu-Myles[SUP] 1 [/SUP], Darwyn Kobasa[SUP] 2 [/SUP], Anh Tran[SUP] 6 [/SUP], Wangxue Chen[SUP] 7 [/SUP], Xu Zhang[SUP] 3 [/SUP], David Safronetz[SUP] 8 [/SUP], Xuguang Li[SUP] 9 [/SUP]
Affiliations
- PMID: 41015121
- DOI: 10.1016/j.antiviral.2025.106284
Influenza A viruses are categorized into two phylogenetic groups (group 1 and group 2) based on the structure of their hemagglutinin (HA) protein. Within group 2, H3N2 poses a particular challenge due to its rapid evolution, limited vaccine efficacy, and association with more severe influenza seasons. Although T cell responses have been extensively studied in the context of vaccine-induced protection, HA stem (HA2)-specific T cell responses have been relatively understudied, especially those related to nasal immunity. To address this, we engineered an adenoviral vector vaccine (Ad-HA2) expressing a consensus hemagglutinin stem sequence, derived through bioinformatic analysis of all H3 strains. The vaccine conferred heterosubtypic protection against lethal challenges with either H3N2 or H7N9, both belonging to group 2 influenza A viruses, with protection lasting at least six months post-vaccination. Notably, the vaccine induced robust HA2-specific humoral and cell-mediated responses in the nasal-associated lymphoid tissue (NALT) of the upper respiratory tract, the first line of immune defense against inhaled pathogens. The vaccine also elicited significant levels of antibodies and T cell responses in the lower respiratory tract and pulmonary immune sites. Furthermore, circulating antibodies in the serum demonstrated effective antibody-dependent cellular cytotoxicity (ADCC) activity. Finally, using a peptide pool matrix screening approach combined with in silico verification, we identified an immunogenic C-terminus region of the HA2 consensus sequence that activated CD4+ and CD8+ T cells, which warrants further investigation. Collectively, these findings are informative for the design and evaluation of mucosal influenza vaccines targeting the hemagglutinin stem.
Keywords: H3N2; H5N1; T cell; hemagglutinin stem; influenza; mucosal vaccine.