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A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection
Zeng, Dian1; Xin, Jiabao2; Yang, Kunyu3; Guo, Shuxin4; Wang, Qian1; Gao, Ying1; Chen, Huiqing1; Ge, Jiaqi1; Lu, Zhen2; Zhang, Limin1; Chen, Junyu2; Chen, Yixin1; Xia, Ningshao1
2022-06-01
Source PublicationViruses
Volume14Issue:6
Abstract

Two lineages of influenza B viruses (IBV) co-circulating in human beings have been posing a significant public health burden worldwide. A substantial number of broadly neutralizing antibodies (bnAbs) have been identified targeting conserved epitopes on hemagglutinin (HA) stem domain, posing great interest for universal influenza vaccine development. Various strategies to design immunogens that selectively present these conserved epitopes are being explored. However, it has been a challenge to retain native conformation of the HA stem region, especially for soluble expression in prokaryotic systems. Here, using a structure prediction tool AlphaFold2, we rationally designed a stable stem antigen “B60-Stem-8071”, an HA stem vaccine derived from B/Brisbane/60/2006 grafted with a CR8071 epitope as a linker. The B60-Stem-8071 exhibited better solubility and more stable expression in the E. coli system compared to the naïve HA stem antigen. Immunization with B60-Stem-8071 in mice generated cross-reactive antibodies and protected mice broadly against lethal challenge with Yamagata and Victoria lineages of influenza B virus. Notably, soluble expression of B60-stem-8071 in the E. coli system showed the potential to produce the influenza B vaccine in a low-cost way. This study represents a proof of concept for the rational design of HA stem antigen based on structure prediction and analysis.

KeywordAlphafold2 Broad Protection Influenza b Viruses (Ibv) Stem Hemagglutinin (Ha) Structure Prediction Vaccine Design
DOI10.3390/v14061305
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaVirology
WOS SubjectVirology
WOS IDWOS:000816564000001
Scopus ID2-s2.0-85132587475
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Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorChen, Yixin
Affiliation1.State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, 361102, China
2.State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, 361102, China
3.Xiamen International Travel Healthcare Center, Xiamen, 361012, China
4.Faculty of Health Sciences, University of Macau, 999078, Macao
Recommended Citation
GB/T 7714
Zeng, Dian,Xin, Jiabao,Yang, Kunyu,et al. A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection[J]. Viruses,2022,14(6).
APA Zeng, Dian,Xin, Jiabao,Yang, Kunyu,Guo, Shuxin,Wang, Qian,Gao, Ying,Chen, Huiqing,Ge, Jiaqi,Lu, Zhen,Zhang, Limin,Chen, Junyu,Chen, Yixin,&Xia, Ningshao.(2022).A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection.Viruses,14(6).
MLA Zeng, Dian,et al."A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection".Viruses 14.6(2022).
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