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Cell:a new method for efficient prevention of Omicron

On April 26, Beijing Academy of life sciences, Chinese Academy of SciencesAcademician Gao Fu, director of cryoelectron microscope center of South University of science and technologyProfessor Wang PeiyiInstitute of Microbiology, Chinese Academy of SciencesResearcher Dai LianpanInstitute of medical biology, Chinese Academy of Medical SciencesResearcher Peng Xiaozhong, chief biosafety expert of China Center for Disease Control and prevention and director of BSL-3 Laboratory of Institute for viral disease control and PreventionWu GUIResearcher ZhenAs a co corresponding author, he published in the cell journal entitled:Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2 Research papers.

Research teamThe design method of chimeric receptor binding domain (RBD) dimer protein vaccine rapidly adapted to the epidemic variant of COVID-19 was developed, which is formed by two heterologous RBDS in series. Compared with homologous RBD dimer, chimeric RBD dimer can stimulate a wider spectrum of antibody response and provide better protective effect in animals.

Mice and rhesus monkeys immunized with the prototype beta chimeric RBD dimer protein vaccine designed with this strategy showed protective effects on a variety of mutant strains in the challenge experiment,The designed Delta Omicron chimeric RBD dimer vaccine effectively protected mice from Delta and Omicron infection and pneumonia.

The spike (s) protein on the surface of novel coronavirus is responsible for virus receptor recognition and membrane fusion. RBD on S protein is an important vaccine target. It stimulates the production of neutralizing antibodies and has the advantage of immune focusing.

前期Academician Gao Fu团队提出了β冠状病毒S蛋白的RBD二聚体疫苗设计理念,发现将新冠病毒RBD进行串联重复设计成的二聚体抗原免疫小鼠血清的中和抗体滴度高于单体的免疫效果(Dai et al, 2020, Cell)。

Based on this concept,Institute of Microbiology, CAS AndZhifei biologyJointly developedCOVID-19 recombinant protein vaccine zf2001 showed good safety and immunogenicity in phase i/ii clinical trials(Yang et al, 2021, Lancet Infectious Diseases), the results of phase III clinical trial showed that after three doses of zf2001, the protective efficacy of the vaccine against COVID-19 of any severity in people aged 18 and above was 81.43%, including 92.87%for severe and above diseases.

The vaccine was approved for emergency use by China and Uzbekistan in March 2021. It is the first new coronal recombinant protein vaccine approved for use in the worldAfter that, it was also approved for emergency use in Indonesia and Colombia. In addition, zf2001 was approved for conditional listing in China this year and as a sequential booster of the new crown inactivated vaccine. Recombinant subunit protein vaccine has the advantages of high yield, high safety, easy storage and transportation. It is one of the important choices to prevent COVID-19.

At present, the epidemic situation of COVID-19 is still very serious in the world. Novel coronavirus variants continue to appear and prevail. Some of them will escape the antibody immune response of existing vaccines and cause breakthrough infection. In particular, Delta and Omicron mutants have swept the world in turn and become dominant epidemic strains, which has brought severe challenges to epidemic prevention and control. Therefore, it is crucial to develop a vaccine with broad-spectrum preventive effect on mutant strains including Omicron.

Based on the design of the prototype strain homologous RBD dimer protein vaccine (zf2001), the researchers developed a heterologous RBD dimer protein vaccine design method for rapid adaptation to the new coronavirus variant strain. Based on this, the prototype beta chimeric protein vaccine was first designed, and its antibody response and protective effect were verified in mice, And the protection of rhesus monkeys against a variety of new coronavirus strains can be provided by immunizing rhesus monkeys with prototype beta chimeric protein vaccine.

之后,研究者们设计了Delta-Omicron嵌合蛋白疫苗,Andprototype同源RBD二聚体疫苗相比,其免疫小鼠刺激产生更加广谱的抗体反应,对Delta和Omicron变异株的攻毒均表现出更好的保护效果,这些研究数据支持开发适应变异株的多价疫苗以预防流行变异株,该研究在当前Omicron变异株流行的背景下给疫情防控提供极大的支持。

Paper link:

https://www.cell.com/cell/fulltext/S0092-8674 (22)00527-X