A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection
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 in...
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MDPI AG
2022-06-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/6/1305 |
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| author | Dian Zeng Jiabao Xin Kunyu Yang Shuxin Guo Qian Wang Ying Gao Huiqing Chen Jiaqi Ge Zhen Lu Limin Zhang Junyu Chen Yixin Chen Ningshao Xia |
| author_facet | Dian Zeng Jiabao Xin Kunyu Yang Shuxin Guo Qian Wang Ying Gao Huiqing Chen Jiaqi Ge Zhen Lu Limin Zhang Junyu Chen Yixin Chen Ningshao Xia |
| author_sort | Dian Zeng |
| collection | DOAJ |
| description | 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 <i>E. coli</i> 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 <i>E. coli</i> 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. |
| first_indexed | 2024-03-09T22:13:24Z |
| format | Article |
| id | doaj.art-772285aee0ce4e67a1a698d975f233a1 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T22:13:24Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-772285aee0ce4e67a1a698d975f233a12023-11-23T19:27:09ZengMDPI AGViruses1999-49152022-06-01146130510.3390/v14061305A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B InfectionDian Zeng0Jiabao Xin1Kunyu Yang2Shuxin Guo3Qian Wang4Ying Gao5Huiqing Chen6Jiaqi Ge7Zhen Lu8Limin Zhang9Junyu Chen10Yixin Chen11Ningshao Xia12State 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, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, ChinaXiamen International Travel Healthcare Center, Xiamen 361012, ChinaFaculty of Health Sciences, University of Macau, Macau SAR 999078, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, ChinaState 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, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, ChinaState 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, ChinaState 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, ChinaTwo 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 <i>E. coli</i> 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 <i>E. coli</i> 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.https://www.mdpi.com/1999-4915/14/6/1305influenza B viruses (IBV)stem hemagglutinin (HA)vaccine designstructure predictionAlphaFold2broad protection |
| spellingShingle | Dian Zeng Jiabao Xin Kunyu Yang Shuxin Guo Qian Wang Ying Gao Huiqing Chen Jiaqi Ge Zhen Lu Limin Zhang Junyu Chen Yixin Chen Ningshao Xia A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection Viruses influenza B viruses (IBV) stem hemagglutinin (HA) vaccine design structure prediction AlphaFold2 broad protection |
| title | A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection |
| title_full | A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection |
| title_fullStr | A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection |
| title_full_unstemmed | A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection |
| title_short | A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection |
| title_sort | hemagglutinin stem vaccine designed rationally by alphafold2 confers broad protection against influenza b infection |
| topic | influenza B viruses (IBV) stem hemagglutinin (HA) vaccine design structure prediction AlphaFold2 broad protection |
| url | https://www.mdpi.com/1999-4915/14/6/1305 |
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