A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection.

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.
Authors	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
Journal	Viruses (Viruses) Vol. 14 Issue 6 (06 14 2022) ISSN: 1999-4915 [Electronic] Switzerland
PMID	35746776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antibodies, Neutralizing Antibodies, Viral Epitopes Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinins Influenza Vaccines
Topics	Animals Antibodies, Neutralizing Antibodies, Viral Epitopes Escherichia coli (metabolism) Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinins Humans Influenza B virus Influenza Vaccines Influenza, Human Mice Orthomyxoviridae Infections

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!