Intranasal adenoviral neuraminidase vaccine induces local and systemic immunity and homosubtypic protection against influenza A viruses
- 1Department of Comparative Pathobiology, and Purdue Institute of Inflammation, Immunology and Infectious Disease, College of Veterinary Medicine, Purdue University
- 2Influenza Division, Centers for Disease Control and Prevention
Abstract
Introduction: The rapid antigenic drift of influenza A hemagglutinin (HA) limits the effectiveness of current HA-focused vaccines. To address this challenge, we evaluated recombinant human (HAd) and bovine (BAd) adenoviral vectors expressing neuraminidase (NA) as an alternative strategy to elicit broad and protective mucosal immunity.
Methods: BALB/c mice were immunized intranasally with HAd- or BAd-based vectors expressing N9 NA. Antigen-specific cellular and humoral immune responses were quantified locally and systemically. Immunized mice were subsequently monitored for survival and protective efficacy following lethal homosubtypic or heterosubtypic (Group 1 [H1N1] and Group 2 [H3N2]) influenza A viral challenges.
Results: Intranasal immunization with both vectors induced strong systemic IgG and mucosal IgA responses, as well as robust systemic and local T-cell activation, providing complete protection against lethal homosubtypic challenge. Notably, the BAd-N9NA vector elicited stronger mucosal and cellular responses than the HAd-based counterpart. Regarding cross-protection, N9-based vaccination conferred partial protection against the Group 2 (H3N2) virus but failed against the Group 1 (H1N1) virus.
Discussion: These findings demonstrate that NA-expressing adenoviral vectors induce potent mucosal and cellular immunity that mediates strong homosubtypic protection. While conserved structural epitopes exist across N1, N2, and N9 subtypes, heterosubtypic protection is limited and remains constrained by phylogenetic group lineages and sequence conservation. Furthermore, these results highlight the BAd platform as a highly potent delivery system for maximizing NA-specific immunogenicity, offering valuable insights for the design of broadly protective NA-based vaccines.
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BibTeX
@article{wang2026intranasal,
title = {{Intranasal adenoviral neuraminidase vaccine induces local and systemic immunity and homosubtypic protection against influenza A viruses}},
author = {Wen-Chien Wang and Weiping Cao and Amrita Kumar and Wadzanai P. Mboko and Ram Kamal and Ekramy E. Sayedahmed and Suresh K. Mittal},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1911139},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1911139/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Intranasal adenoviral neuraminidase vaccine induces local and systemic immunity and homosubtypic protection against influenza A viruses
AU - Wen-Chien Wang
AU - Weiping Cao
AU - Amrita Kumar
AU - Wadzanai P. Mboko
AU - Ram Kamal
AU - Ekramy E. Sayedahmed
AU - Suresh K. Mittal
PY - 2026
DA - 2026/10/22
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1911139
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1911139/full
AB - Introduction: The rapid antigenic drift of influenza A hemagglutinin (HA) limits the effectiveness of current HA-focused vaccines. To address this challenge, we evaluated recombinant human (HAd) and bovine (BAd) adenoviral vectors expressing neuraminidase (NA) as an alternative strategy to elicit broad and protective mucosal immunity. Methods: BALB/c mice were immunized intranasally with HAd- or BAd-based vectors expressing N9 NA. Antigen-specific cellular and humoral immune responses were quantified locally and systemically. Immunized mice were subsequently monitored for survival and protective efficacy following lethal homosubtypic or heterosubtypic (Group 1 [H1N1] and Group 2 [H3N2]) influenza A viral challenges. Results: Intranasal immunization with both vectors induced strong systemic IgG and mucosal IgA responses, as well as robust systemic and local T-cell activation, providing complete protection against lethal homosubtypic challenge. Notably, the BAd-N9NA vector elicited stronger mucosal and cellular responses than the HAd-based counterpart. Regarding cross-protection, N9-based vaccination conferred partial protection against the Group 2 (H3N2) virus but failed against the Group 1 (H1N1) virus. Discussion: These findings demonstrate that NA-expressing adenoviral vectors induce potent mucosal and cellular immunity that mediates strong homosubtypic protection. While conserved structural epitopes exist across N1, N2, and N9 subtypes, heterosubtypic protection is limited and remains constrained by phylogenetic group lineages and sequence conservation. Furthermore, these results highlight the BAd platform as a highly potent delivery system for maximizing NA-specific immunogenicity, offering valuable insights for the design of broadly protective NA-based vaccines.
SN - 1664-3224
ER -