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A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection

Yansheng Li, View ORCID ProfileMingkai Xu, Yongqiang Li, Wu Gu, Gulinare Halimu, Yuqi Li, Zhichun Zhang, Libao Zhou, Hui Liao, Songyuan Yao, Huiwen Zhang, Chenggang Zhang
doi: https://doi.org/10.1101/2021.07.08.451596
Yansheng Li
aInstitute of Applied Ecology, Chinese Academy of Sciences, 72 WenHua Road, Shenyang 110016, PR China
bUniversity of Chinese Academy of Sciences, 19 YuQuan Road, Beijing 100049, PR China
cKey Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, 72 WenHua Road, Shenyang 110016, PR China
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Mingkai Xu
aInstitute of Applied Ecology, Chinese Academy of Sciences, 72 WenHua Road, Shenyang 110016, PR China
cKey Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, 72 WenHua Road, Shenyang 110016, PR China
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  • ORCID record for Mingkai Xu
  • For correspondence: mkxu@iae.ac.cn
Yongqiang Li
aInstitute of Applied Ecology, Chinese Academy of Sciences, 72 WenHua Road, Shenyang 110016, PR China
bUniversity of Chinese Academy of Sciences, 19 YuQuan Road, Beijing 100049, PR China
cKey Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, 72 WenHua Road, Shenyang 110016, PR China
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Wu Gu
aInstitute of Applied Ecology, Chinese Academy of Sciences, 72 WenHua Road, Shenyang 110016, PR China
cKey Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, 72 WenHua Road, Shenyang 110016, PR China
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Gulinare Halimu
aInstitute of Applied Ecology, Chinese Academy of Sciences, 72 WenHua Road, Shenyang 110016, PR China
bUniversity of Chinese Academy of Sciences, 19 YuQuan Road, Beijing 100049, PR China
cKey Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, 72 WenHua Road, Shenyang 110016, PR China
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Yuqi Li
aInstitute of Applied Ecology, Chinese Academy of Sciences, 72 WenHua Road, Shenyang 110016, PR China
bUniversity of Chinese Academy of Sciences, 19 YuQuan Road, Beijing 100049, PR China
cKey Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, 72 WenHua Road, Shenyang 110016, PR China
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Zhichun Zhang
aInstitute of Applied Ecology, Chinese Academy of Sciences, 72 WenHua Road, Shenyang 110016, PR China
bUniversity of Chinese Academy of Sciences, 19 YuQuan Road, Beijing 100049, PR China
cKey Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, 72 WenHua Road, Shenyang 110016, PR China
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Libao Zhou
dChengda Biotechnology Co.Ltd., Liaoning, China
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Hui Liao
dChengda Biotechnology Co.Ltd., Liaoning, China
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Songyuan Yao
dChengda Biotechnology Co.Ltd., Liaoning, China
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Huiwen Zhang
aInstitute of Applied Ecology, Chinese Academy of Sciences, 72 WenHua Road, Shenyang 110016, PR China
cKey Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, 72 WenHua Road, Shenyang 110016, PR China
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Chenggang Zhang
aInstitute of Applied Ecology, Chinese Academy of Sciences, 72 WenHua Road, Shenyang 110016, PR China
cKey Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, 72 WenHua Road, Shenyang 110016, PR China
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Abstract

Influenza pandemic poses public health threats annually for lacking vaccine which provides cross-protection against novel and emerging influenza viruses. Combining conserved antigens inducing cross-protective antibody response with epitopes activating cross-protective cytotoxic T-cells would offer an attractive strategy for developing universal vaccine. In this study, we constructed a recombinant protein NMHC consisting of influenza viral conserved epitopes and superantigen fragment. NMHC promoted the mature of bone marrow-derived dendritic cells and induced CD4+ T cells to differentiate into Th1, Th2 and Th17 subtypes. Mice vaccinated with NMHC produced high level of immunoglobulins which cross-bound to HA fragments from six influenza virus subtypes with high antibody titers. Anti-NMHC serum showed potent hemagglutinin inhibition effects to highly divergent group 1 (H1 subtypes) and group 2 (H3 subtype) influenza virus strains. And purified anti-NMHC antibodies could bind to multiple HAs with high affinities. NMHC vaccination effectively protected the mice from infection and lung damage challenged by two subtypes of H1N1 influenza virus. Moreover, NMHC vaccination elicited CD4+ and CD8+ T-cell responses to clear the virus from infected tissue and prevent virus spreading. In conclusion, this study provided proof of concept for triggering both B cells and T cells immune responses against multiple influenza virus infection, and NMHC may be a potential candidate of universal broad-spectrum vaccine for various influenza virus prevention and therapy.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Competing Interest Statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 08, 2021.
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A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection
Yansheng Li, Mingkai Xu, Yongqiang Li, Wu Gu, Gulinare Halimu, Yuqi Li, Zhichun Zhang, Libao Zhou, Hui Liao, Songyuan Yao, Huiwen Zhang, Chenggang Zhang
bioRxiv 2021.07.08.451596; doi: https://doi.org/10.1101/2021.07.08.451596
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A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection
Yansheng Li, Mingkai Xu, Yongqiang Li, Wu Gu, Gulinare Halimu, Yuqi Li, Zhichun Zhang, Libao Zhou, Hui Liao, Songyuan Yao, Huiwen Zhang, Chenggang Zhang
bioRxiv 2021.07.08.451596; doi: https://doi.org/10.1101/2021.07.08.451596

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