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Development of a broad-spectrum nasal live attenuated influenza vaccine based on mosaic antigen design against influenza B viruses

delete2025-10-29
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OA
AI
X
Xue Han
R
Run Ma
X
Ximeng Ma
H
Hongwei Chen
T
Tianyi Zhao
X
Xuejie Liu
L
Lin Zhu
L
Lifang Yuan
Y
Yuhang Shi *
Y
Yuhang Zhang
Q
Qi Chen
J
Jian Lü
C
Chen Chen
W
Wantong Pang
T
Tian Bai
W
Wenfei Zhu *
Y
Yuelong Shu *
DOI:10.1080/22221751.2025.2576141delete
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Abstract

Abstract

En 中文
Influenza B virus (IBV) causes significant seasonal disease burden, and frequent antigenic drift limits the effectiveness of conventional vaccines. To address this, we designed mosaic haemagglutinin (HA) and neuraminidase (NA) antigens to maximize T-cell epitope coverage and incorporated them into a nasal live attenuated influenza vaccine (LAIV) platform. Using B/Victoria lineage sequences (2009-2021), mosaic HA/NA candidates were generated via an iterative genetic algorithm. BALB/c mice were randomized into PBS, conventional inactivated influenza vaccine (IIV), conventional LAIV, and mosaic-LAIV (MoBV) groups, and immunized intranasally on days 0 and 14. Immune responses were evaluated by haemagglutination inhibition (HAI), microneutralization (MN), neuraminidase inhibition (NAI), mucosal IgA by ELISA, and T-cell profiling by flow cytometry. Protective efficacy was assessed by challenge with multiple IBV strains. MoBV-induced higher cross-reactive antibody responses (HAI, MN, NAI) and markedly increased mucosal IgA, which persisted for 100 days, alongside enhanced T-cell responses. Upon challenge, MoBV improved survival to 25-100% compared with controls. These results demonstrate that MoBV elicits broad systemic and mucosal immunity, providing robust cross-lineage protection against diverse IBV strains and supporting the development of a universal influenza B vaccine.
Keywords:
Mosaic
influenza B vaccines
mucosal immune
broad spectrum
LAIV
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Emerging Microbes and Infections cover
Emerging Microbes and Infections
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