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...
Main Authors: | , , , , , , , , , , , |
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Language: | English |
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eLife Sciences Publications Ltd
2021-11-01
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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. |
first_indexed | 2024-04-11T09:01:49Z |
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id | doaj.art-72b0fe06823f4dfebd472c389b785b65 |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-11T09:01:49Z |
publishDate | 2021-11-01 |
publisher | eLife Sciences Publications Ltd |
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series | eLife |
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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