A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection
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
Affiliations
Dian Zeng
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
Jiabao Xin
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, China
Kunyu Yang
Xiamen International Travel Healthcare Center, Xiamen 361012, China
Shuxin Guo
Faculty of Health Sciences, University of Macau, Macau SAR 999078, China
Qian Wang
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
Ying Gao
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
Huiqing Chen
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
Jiaqi Ge
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
Zhen Lu
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, China
Limin Zhang
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
Junyu Chen
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, China
Yixin Chen
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
Ningshao Xia
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
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.
