Emerge in an endless stream of mutation COVID-19, from Alfa, beta, gamma to del and Miao virus strains, constantly challenge the epidemic prevention and control in various countries. Among them, delta strain has become the main variant strain prevalent in most parts of the world, and it is more infectious. Why does mutation COVID-19 increase its infectivity? A study recently published by Chinese researchers in the American journal Cell report reveals the “mystery”.
The cunning new crown virus can evolve new dominant variants. According to the data of the “Global Initiative for influenza data sharing” platform of international shared gene sequence resources, alpha strain has dominated the transmission since January 2021. However, since May, delta strain has gradually replaced alpha strain and become a dominant variant in global transmission.
It is found that compared with alpha strain, the spike protein of delta strain can be cut more efficiently by host cell protease to form functional protein, which greatly improves the efficiency of delta strain invading cells, speeds up its replication speed in the early stage of infection, and helps to establish the advantage of delta variant.
In addition to the increased infection ability, the immune escape ability of mutant COVID-19 increased. Compared with the wild type COVID-19, the neutralizing power of the serum neutralizing antibody to the delta strain decreased significantly. The neutralization effect of vaccine and monoclonal antibody drugs for treatment on delta virus strain decreased accordingly.
The latest research by the Tan Xu Laboratory of Tsinghua University School of pharmacy and the Institute of life sciences, University of Science & Technology China, found that in addition to antibody mediated humoral immune escape, the escape of cellular immune responses mediated by killer T cells may also promote the spread of the dominant variants of the new crown disease.
Cellular immunity is another immune system in the human body in addition to antibody immunity. Its main function is to use leukocytes called killer T cells to specifically identify and remove human cells infected by pathogens, so as to achieve the immune effect of blocking the replication and transmission of pathogens.
Previous studies have shown that cellular immune response is related to the severity and development of Xinguan disease. Blood tests showed that the specific cells of COVID-19 could be detected earlier than neutralizing antibodies, indicating that cellular immune responses began to play a role in the early stages of viral infection. This early immunosuppression is very important for the body to defend COVID-19 and suppress the spread of the virus.
But researchers found that some peculiar mechanisms of mutant COVID-19 can help their escape cells immune, leading to further infection. Through the high-throughput screening platform, researchers screened and identified 4 COVID-19 specific key epitopes related to cellular immunity. It was found that at least one of the key epitopes was mutated by Alfa, beta, gamma and delta strains, which helped the disease escape immune recognition of killer T cells. Escaping human cellular immunity is a common feature of the new crown epidemic variants.
In addition, the researchers also screened invariable epitopes in different coronaviruses. The invariance of these epitopes shows that they have important functions for coronaviruses.
Tan Xu, an associate professor at the school of pharmacy at Tsinghua University, said that the escape of the mutant COVID-19 to the immune system has greatly increased the complexity of the global vaccination program. These invariant epitopes provide a theoretical basis for the design of the universal vaccine for the new generation of coronavirus.
The new universal vaccine will not only activate the human body to produce neutralizing antibodies, but also mediate a wide range of cellular immune responses and reduce the risk of mutant virus breakthrough infection (refers to the infection after vaccination).