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Figure Immunogen construction strategy of "lineage chimerism-mutation patch" and its broad-spectrum neutralizing antibody effect
With the support of the National Natural Science Foundation of China (Grant No.
: 81991491), Professor Xia Ningshao of Xiamen University, Professor Guan Yi of the University of Hong Kong, Professor Cao Hua of Fujian Maternal and Child Health Hospital and others have made progress in the new strategy of immunogen construction of broad-spectrum new crown vaccines, and the research results are "Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine", in Cell? Published
in the journal Cell Host & Microbe.
Link to paper: _istranslated="1">.
The continuous emergence of SARS-CoV-2 variants poses great challenges to the effectiveness of vaccines, and amino acid mutations in viral spike protein (S) may cause the virus to escape from natural infection or vaccination-induced immunity, so there is an urgent need to develop a new crown vaccine
that can achieve a broad-spectrum protective effect.
The key to the development of broad-spectrum new crown vaccines is to build immunogens
that can induce broad-spectrum protection.
The research team proposed the immunogen construction strategy of "lineage chimerism-mutation patch", that is, the domain chimeric recombination and mutation modification of S protein are carried out through strains with large differences in antigenicity, and the immunogen combination is evaluated and screened to achieve broader antigen coverage
.
The researchers combined the N-terminal domain of the S-protein of the B.
1.
620 variant with the receptor-binding domain (RBD) and S2 subunit of the Gamma variant, and introduced other RBD mutations that affect antigenicity on this basis, successfully constructing a chimeric immunogen
with strong immunogenicity and complementary antigenicity and prototype S protein (STFK).
。 Among them, the bivalent vaccine composed of STFK and chimeric immunogen induced high-titer broad-spectrum neutralizing antibodies in animals, which effectively neutralized various variants, including Omicron BA.
1, BA.
1.
1, BA.
2, BA.
2.
12.
1, BA.
2.
75, BA.
4 and BA.
5 (Fig).
It is worth mentioning that the new chimeric immunogens have been designed and constructed before the emergence of Omicron variants, but can effectively induce broad-spectrum neutralizing antibodies against various Omicron variants, indicating that the new immunogen construction strategy proposed in this study is forward-looking
.
This study clarifies the antigenic and immunogenic characteristics of the new crown variant S protein, which can provide new ideas
for the development of a universal vaccine for COVID-19.