Professor Xia Ningshao's team proposed a new strategy for immunogen construction of broad-spectrum new crown vaccines

The ongoing COVID-19 pandemic, caused by the novel coronavirus (SARS-CoV-2), has created a significant public health burden
.
Although multiple coronavirus vaccines have been launched, the continuous emergence of SARS-CoV-2 variants poses a huge challenge
to the effectiveness of vaccines.
Viral genomic mutations may alter the biological phenotype
of SARS-CoV-2 in many aspects such as viral infectivity, pathogenicity, and antigenicity.
But more importantly, amino acid mutations in viral spike protein(S) may cause the virus to escape immunity induced by natural infection or vaccination
.
Compared with previous variants, the Omicron (B.
1.
1.
529) variant, including BA.
1, BA.
2, BA.
2.
12.
1, BA.
2.
75, BA.
4 and BA.
5, etc.
, are significantly more
infectious and immune evasive.
The research and development ideas of traditional vaccines may be difficult to cope with the rapid mutation of the new coronavirus, and there is an urgent need to develop broad-spectrum new crown vaccines
that can achieve broad-spectrum protection.

The most critical challenge in the development of broad-spectrum new crown vaccines is how to construct immunogens
that can induce broad-spectrum protection.
To this end, Professor Xia Ningshao's team proposed an immunogen construction strategy of "lineage chimerism-mutation patch", that is, the domain chimeric recombination and mutation transformation of S protein are carried out through strains with large differences in antigenicity, and immunogen combinations with strong immunogenicity and high degree of antigenicity complementarity are evaluated and screened to achieve broader antigen coverage
。 In this study, the researchers combined the N-terminal domain (NTD) of the S-protein of the B.
1.
620 variant with the receptor-binding domain and S2 subunit (RBD-S2) of the Gamma variant, and introduced other RBD mutations that affect antigenicity on this basis, and successfully constructed chimeric immunogens STFK1628x and STFK1628y
with strong immunogenicity and complementary antigenicity and prototype S protein (STFK).
。 Among them, the bivalent vaccine composed of STFK and STFK1628x induced high-titer broad-spectrum neutralizing antibodies in animals, which can effectively neutralize various VOCs and VOI variants, including Omicron BA.
1, BA.
1.
1, BA.
2, BA.
2.
12.
1, BA.
2.
75, BA.
4 and BA.
5
.
In the hamster challenge model, it has been confirmed that the vaccine can effectively protect against the direct attack
of the new crown prototype strain and the Beta and Omicron variants.
What's more, the study also showed that the bivalent vaccine could block transmission of the virus from vaccinated hamsters to unvaccinated individuals
.
It is worth mentioning that the two new immunogens, STFK1628x and STFK1628y, were designed and constructed before the emergence of Omicron, but they 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
.
These findings clarify 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.

Recently, the research results were published online in the research paper entitled "Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine" in the sub-journal "Cell? Cell Host & Microbe
.
Wu Yangtao, postdoctoral fellow, Shaojuan Wang, postdoctoral fellow, Yali Zhang, postdoctoral Yuan Lunzhi, senior engineer Zheng Qingbing, doctoral student Wei Min, and doctoral student Shi Yang of the National Engineering Center are the co-first authors
of the paper.
Professor Xia Ningshao of the National Engineering Center, Professor Guan Yi of the University of Hong Kong, Professor Yuan Quan of the National Engineering Center, Associate Professor Zhu Huachen of the University of Hong Kong, Professor Cao Hua of Fujian Maternal and Child Health Hospital, Professor Zhang Jun and Assistant Professor Zhang Tianying of the National Engineering Center are the co-corresponding authors
of the paper.
The research was supported
by the National Natural Science Foundation of China, the Natural Science Foundation of Fujian Province, and the Xiamen Science and Technology Program.

Links to papers:

class="vsbcontent_end" style="text-align: right;" _msthash="101743" _msttexthash="6640218">(Photo/Text National Engineering Research Center for Infectious Disease Diagnostic Reagents and Vaccines)