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

Influenza pandemics pose public health threats annually for lacking vaccine that provides cross-protection against novel and emerging influenza viruses. Combining conserved antigens that induce cross-protective antibody responses with epitopes that activate cross-protective T cell responses might be...

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Main Authors: Yansheng Li, Mingkai Xu, Yongqiang Li, Wu Gu, Gulinare Halimu, Yuqi Li, Zhichun Zhang, Libao Zhou, Hui Liao, Songyuan Yao, Huiwen Zhang, Chenggang Zhang
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-11-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/71725
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author Yansheng Li
Mingkai Xu
Yongqiang Li
Wu Gu
Gulinare Halimu
Yuqi Li
Zhichun Zhang
Libao Zhou
Hui Liao
Songyuan Yao
Huiwen Zhang
Chenggang Zhang
author_facet Yansheng Li
Mingkai Xu
Yongqiang Li
Wu Gu
Gulinare Halimu
Yuqi Li
Zhichun Zhang
Libao Zhou
Hui Liao
Songyuan Yao
Huiwen Zhang
Chenggang Zhang
author_sort Yansheng Li
collection DOAJ
description Influenza pandemics pose public health threats annually for lacking vaccine that provides cross-protection against novel and emerging influenza viruses. Combining conserved antigens that induce cross-protective antibody responses with epitopes that activate cross-protective T cell responses might be an attractive strategy for developing a universal vaccine. In this study, we constructed a recombinant protein named NMHC that consists of influenza viral conserved epitopes and a superantigen fragment. NMHC promoted the maturation 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 levels of immunoglobulins that 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 subtype) and group 2 (H3 subtype) influenza virus strains. Furthermore, purified anti-NMHC antibodies bound to multiple HAs with high affinities. NMHC vaccination effectively protected mice from infection and lung damage when exposed to two subtypes of H1N1 influenza virus. Moreover, NMHC vaccination elicited CD4+ and CD8+ T cell responses that cleared the virus from infected tissues and prevented virus spread. In conclusion, this study provides proof of concept that NMHC vaccination triggers B and T cell immune responses against multiple influenza virus infections. Therefore, NMHC might be a candidate universal broad-spectrum vaccine for the prevention and treatment of multiple influenza viruses.
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spelling doaj.art-72b0fe06823f4dfebd472c389b785b652022-12-22T04:32:46ZengeLife Sciences Publications LtdeLife2050-084X2021-11-011010.7554/eLife.71725A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protectionYansheng Li0Mingkai Xu1https://orcid.org/0000-0001-9889-6287Yongqiang Li2Wu Gu3Gulinare Halimu4Yuqi Li5Zhichun Zhang6Libao Zhou7Hui Liao8Songyuan Yao9Huiwen Zhang10Chenggang Zhang11Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, Shenyang, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China; Key Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, Shenyang, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, Shenyang, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China; Key Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, Shenyang, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, Shenyang, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, Shenyang, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, Shenyang, ChinaChengda Biotechnology Co. Ltd, Liaoning, ChinaChengda Biotechnology Co. Ltd, Liaoning, ChinaChengda Biotechnology Co. Ltd, Liaoning, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China; Key Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, Shenyang, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China; Key Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, Shenyang, ChinaInfluenza pandemics pose public health threats annually for lacking vaccine that provides cross-protection against novel and emerging influenza viruses. Combining conserved antigens that induce cross-protective antibody responses with epitopes that activate cross-protective T cell responses might be an attractive strategy for developing a universal vaccine. In this study, we constructed a recombinant protein named NMHC that consists of influenza viral conserved epitopes and a superantigen fragment. NMHC promoted the maturation 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 levels of immunoglobulins that 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 subtype) and group 2 (H3 subtype) influenza virus strains. Furthermore, purified anti-NMHC antibodies bound to multiple HAs with high affinities. NMHC vaccination effectively protected mice from infection and lung damage when exposed to two subtypes of H1N1 influenza virus. Moreover, NMHC vaccination elicited CD4+ and CD8+ T cell responses that cleared the virus from infected tissues and prevented virus spread. In conclusion, this study provides proof of concept that NMHC vaccination triggers B and T cell immune responses against multiple influenza virus infections. Therefore, NMHC might be a candidate universal broad-spectrum vaccine for the prevention and treatment of multiple influenza viruses.https://elifesciences.org/articles/71725hemagglutinin stalksuperantigencross-protectioncell-mediated immunity
spellingShingle Yansheng Li
Mingkai Xu
Yongqiang Li
Wu Gu
Gulinare Halimu
Yuqi Li
Zhichun Zhang
Libao Zhou
Hui Liao
Songyuan Yao
Huiwen Zhang
Chenggang Zhang
A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection
eLife
hemagglutinin stalk
superantigen
cross-protection
cell-mediated immunity
title A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection
title_full A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection
title_fullStr A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection
title_full_unstemmed A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection
title_short A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection
title_sort recombinant protein containing influenza viral conserved epitopes and superantigen induces broad spectrum protection
topic hemagglutinin stalk
superantigen
cross-protection
cell-mediated immunity
url https://elifesciences.org/articles/71725
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