tetano
Editor, Senior Moderator
Vaccine
. 2026 Nov 11:96:129318.
doi: 10.1016/j.vaccine.2026.129318. Online ahead of print.
Yawei Wang 1 , Juan Ma 1 , Jingbin Huang 2 , Liye Jin 1 , Yujie Jiang 2 , Wenling Wang 1 , Yao Deng 1 , Baoying Huang 3 , Wenjie Tan 4
Affiliations Expand
The rapid antigenic drift of influenza surface glycoproteins frequently causes "antigenic mismatch," severely compromising seasonal vaccine efficacy. To address this, we evaluated an immunization strategy wherein quadrivalent inactivated vaccine (QIV) pre-immunization is followed by a multi-epitope peptide boost. This peptide mixture comprises highly conserved, HLA-A*11:01-restricted CD8+ T-cell epitopes from internal viral proteins (NP, M1, PB1). In HLA-A*11:01 transgenic (Tg) mice, this QIV/5Pep-Mix regimen selectively amplified measurable, epitope-specific IFN-γ+ CD8+ T-cell responses. Following lethal heterologous challenge with the PR8 strain, the peptide-immunized Tg mice achieved 100% survival, accelerated weight recovery, reduced pulmonary viral titers, and attenuated lung histopathology. Crucially, this cross-protection was primarily driven by CD8+ T-cell-mediated immunity, as humoral cross-reactivity (HAI, IgG, neutralizing antibodies) against PR8 was negligible. Furthermore, protective efficacy was completely abolished in wild-type mice, confirming strict dependence on HLA-A*11:01 presentation. These findings demonstrate that an epitope-based "add-on" strategy effectively bridges the gap left by strain-mismatched antibody responses. This approach offers a promising platform for universal influenza vaccines in high-frequency HLA populations, providing a reliable second line of defense against seasonal drift and pandemics.
Keywords: CD8(+) T-cell epitopes; Cross-protection; HLA-A*11:01; Influenza virus; Pre-existing immunity; Universal vaccine.
. 2026 Nov 11:96:129318.
doi: 10.1016/j.vaccine.2026.129318. Online ahead of print.
HLA-A*11:01-restricted CD8
Yawei Wang 1 , Juan Ma 1 , Jingbin Huang 2 , Liye Jin 1 , Yujie Jiang 2 , Wenling Wang 1 , Yao Deng 1 , Baoying Huang 3 , Wenjie Tan 4
Affiliations Expand
- PMID: 43014058
- DOI: 10.1016/j.vaccine.2026.129318
Abstract
The rapid antigenic drift of influenza surface glycoproteins frequently causes "antigenic mismatch," severely compromising seasonal vaccine efficacy. To address this, we evaluated an immunization strategy wherein quadrivalent inactivated vaccine (QIV) pre-immunization is followed by a multi-epitope peptide boost. This peptide mixture comprises highly conserved, HLA-A*11:01-restricted CD8+ T-cell epitopes from internal viral proteins (NP, M1, PB1). In HLA-A*11:01 transgenic (Tg) mice, this QIV/5Pep-Mix regimen selectively amplified measurable, epitope-specific IFN-γ+ CD8+ T-cell responses. Following lethal heterologous challenge with the PR8 strain, the peptide-immunized Tg mice achieved 100% survival, accelerated weight recovery, reduced pulmonary viral titers, and attenuated lung histopathology. Crucially, this cross-protection was primarily driven by CD8+ T-cell-mediated immunity, as humoral cross-reactivity (HAI, IgG, neutralizing antibodies) against PR8 was negligible. Furthermore, protective efficacy was completely abolished in wild-type mice, confirming strict dependence on HLA-A*11:01 presentation. These findings demonstrate that an epitope-based "add-on" strategy effectively bridges the gap left by strain-mismatched antibody responses. This approach offers a promising platform for universal influenza vaccines in high-frequency HLA populations, providing a reliable second line of defense against seasonal drift and pandemics.
Keywords: CD8(+) T-cell epitopes; Cross-protection; HLA-A*11:01; Influenza virus; Pre-existing immunity; Universal vaccine.