Immune response of T cell is essential for COVID-19 vaccines
Immune response of T cell is essential for COVID-19 vaccines. Throughout history, the invention of vaccines can be described as a milestone in the history of human development. Only then did humans have the initiative to fight infectious diseases. The COVID-19 pandemic caused by the SARS-CoV-2 virus that began at the beginning of this year is the biggest challenge in the public health field in the past century. Only a safe and efficient COVID-19 vaccine is the hope of winning this battle.
At present, the world has not yet fully understood the protective immune response of SARS-CoV-2 virus infection. Therefore, a variety of vaccine platforms and vaccine development strategies worldwide are paralleled to seek rapid breakthroughs. As of November 12 this year, a total of 48 COVID-19 vaccines around the world are in clinical development, and 164 are in pre-clinical development (Figure 1).
At present, the successful antiviral vaccines on the market, such as influenza and measles vaccines, mostly rely on inducing antibody immune response to exert protection. However, there is evidence that in the process of SARS-CoV-2 virus infection, only inducing a neutralizing antibody response does not To fully protect the body, the participation of T cell immune response plays a pivotal role.
Although the neutralizing antibody titers induced by the previous SARS and MERS vaccine candidates are positively correlated with the lung infection index and survival rate of experimental animals, studies believe that serum neutralizing antibodies alone cannot fully protect patients with COVID-19 infection. Studies have shown that although some severely ill patients with COVID-19 disease in ICU contain SARS-CoV-2 specific antibodies, the strength of the antibody response is positively correlated with the severity of the disease, suggesting the role of antibody response in SARS-CoV-2 virus infection More complicated than imagined.
On the one hand, insufficient neutralizing antibody titers can worsen antibody-dependent enhancement (ADE) disease: the virus binds to Fc γ receptors through antibodies and infects more types of cells including macrophages, leading to immune response disorders and inflammation Abnormal secretion of cytokines and chemokines (macrophage activation syndrome); on the other hand, the non-neutralizing antibodies that exist at the same time also have the effect of ADE.
Studies have found that some asymptomatic infected persons have a much smaller body antibody response after several weeks of infection and weaken more rapidly than those with symptomatic infections; even 33% of convalescent patients have little or no specific anti-SARS-CoV-2 Sex antibody.
In contrast, all patients with COVID-19 during the recovery period contain S protein-specific CD4 + T cells, and the proportion of recovered patients with S protein-specific CD8 + T cells is as high as 70%;
Convalescent patients contain a large number of neutralizing antibodies and T cells at the same time, and there are far more memory CD8 + T cells in the respiratory tract of patients with mild infections than those with severe infections. These are consistent with preclinical studies that T cells can protect the body The results of SARS virus infection are consistent.
T cell response activation can not only show a protective effect during the virus infection process, but memory T cells are also indispensable in the long-term protection of the late vaccine. Taking SARS patients as an example, the B cell and neutralizing antibody response of most patients can only be maintained for two years, which may lead to the escape of SARS virus antigen and subsequent reinfection, but T cell memory can maintain >6- For 17 years, and targeting completely different antigenic sites from B cells, especially targeting virus conserved proteins, it greatly reduces the possibility of virus escape.