A cocktail vaccine with monkeypox virus antigens confers protection without selecting mutations in potential immune evasion genes in the vaccinia WR strain challenge
文献类型: 外文期刊
作者: Sun, Xintong;Zhang, Luhua;Chen, Guohua;Yang, Fan;Ning, Xiaoyu;Qiu, Jinxin;Gao, Yuxuan;Yang, Jianshe;Zhang, Wenhui;Zhang, Zihui;Zhang, Yueyue;Li, Siyuan;Zeng, Mingcong;Fu, Baoquan;Li, Yongfeng;Peng, Chen;Li, Weike
作者机构:
关键词: monkeypox virus;cocktail vaccine;viral evolution;vesicular stomatitis virus vector;cross-protective immunity
期刊名称: MBIO
ISSN:
年卷期: 2025 年
页码:
收录情况: SCIE(2025版)
摘要: Faced with the global monkeypox outbreak, current vaccine development predominantly focuses on the mRNA platform despite its limitations in stability and long-term efficacy. Here, we engineered a recombinant vesicular stomatitis virus (rVSV)-vectored cocktail vaccine encoding four conserved monkeypox virus (MPXV) antigens (A35R, A29L, M1R, and B6R; >94% clade homology), leveraging the thermostable properties of the VSV platform validated for 4 degrees C storage in Ebola vaccines. In BALB/c mice, this multi-antigen vaccine elicited a rapid humoral response with specific IgG detectable by day 7, effectively neutralized the virus, and induced a robust Th1/Th2 balanced cytokine response. Immunization conferred 100% survival against lethal vaccinia virus WR strain challenge, with undetectable viral loads in the lungs and serum, and sustained efficacy against secondary infection at 60 days. Histopathology confirmed minimal lung damage in vaccinated mice. Crucially, upon the successive challenges, mutations in key poxvirus immune evasion genes (E3L and B7R) emerged in the single-component vaccine groups but were absent in the cocktail vaccine group. This finding provides direct evidence that the cocktail strategy suppresses viral escape, underscoring a fundamental advantage over single-antigen approaches. Our findings demonstrate the rVSV-based cocktail vaccines as a potent, scalable, and thermostable candidate for global MPXV control, particularly in regions with limited settings.
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