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Second-generation COVID-19 vaccine: Play the role of T cells!
Second-generation COVID-19 vaccine: Play the role of T cells!. As we seek to prevent the COVID-19 (COVID-19 Pneumonia) pandemic through vaccination, we have been short-sighted and focused on inducing antibodies against spike proteins.
With the emergence of the SARS-CoV-2 (new coronavirus) mutant virus, which reduces the ability of these antibodies to prevent infection, people are beginning to worry that we will not be able to contain the pandemic of this disease. Such concerns seem to ignore another important branch of the adaptive immune response: T cells.
Antiviral antibodies can prevent cell infection, but when the antibody titer is low several years after infection or vaccination, some cells will inevitably be infected. In this case, T cells will come to rescue. Cytotoxic T cells (CTL) can detect that a cell is infected and kill it (as shown in the picture above). T cells perceive virus-infected cells (virus-infected cells) through viral peptides presented by the major histocompatibility complex (MHC) on the plasma membrane. Almost any viral protein can produce this T cell polypeptide. In contrast, only certain viral proteins, such as the SARS-CoV-2 spike protein, can produce antibodies that prevent infection.
In the past year, the response of T cells to SARS-CoV-2 infection has been largely ignored. Of course, some laboratories have already studied the patient’s T cell response, and vaccine manufacturers have also dutifully performed the T cell response test and the neutralizing antibody test at the same time. However, relevant discussions have never touched on the importance of T cells in solving the problem of epidemics, and T cells are important for the control of most viral infections. Because T cells can kill cells infected by viruses, which can help prevent diseases and stop infections.
Recent studies have found that the amino acid changes in the spike protein of the SARS-CoV-2 variant do not affect the reactivity of T cells (see Reference 1), which is very good news. In this study, the author synthesized a number of short peptides covering the whole proteome of various SARS-CoV-2 isolates, including the original Wuhan strain and mutant strains B.1.1.7, B.1.351, P.1 and CAL.20C. They found that there was almost no difference in the ability of T cells to recognize these viral polypeptides, whether it was a convalescent patient or a vaccinated patient. This result means that the amino acid changes in the mutant are unlikely to affect the ability of T cells to clear infection.
This observation explains why some COVID-19 vaccines can effectively prevent hospitalization and death even in areas where the variant is widely spread. In some cases, the sera of vaccinated individuals have a reduced ability to neutralize certain mutant virus infections. However, since T cells can still recognize virus-infected mutant cells and eliminate them, the vaccine can prevent severe COVID-19 infection and death.
In fact, it is very unlikely that vaccination will completely stop SARS-CoV-2 infection. After infection or vaccination, the antibody level will drop rapidly, especially in the local respiratory tract mucosa. When the virus enters the nasopharynx of an immune individual, it encounters only a few antibodies against it, which can cause infection. However, memory B cells and T cells will act immediately and produce virus-specific antibodies and T cells within a few days. Antibodies will limit infection, and T cells will eliminate virus-infected cells. The result is that only mild or asymptomatic infections can occur, and it is very likely that they will not be transmitted to others.
Recent observations have shown that vaccination seems to prevent asymptomatic infections, and this issue requires specific analysis. These studies were conducted shortly after vaccination, when the antibody levels in serum and mucosa were high. If these studies were conducted one year after immunization, the results could be very different.
Now imagine that you have completed the vaccination and are infected with a SARS-CoV-2 variant virus. Even if there is a memory response, the virus may begin to multiply well in the nasopharynx because the antibodies are not enough to prevent infection. T cells begin to play a rescue role: T cell epitopes (epitopes) on the surface of infected cells are easy to identify, because they are still basically the same in the SARS-CoV-2 variant compared with the original strain. You may have a mild infection, but you will not be hospitalized or die. This is exactly what the vaccination hopes to achieve.
Why don’t T cell epitopes change like B cell (antibody producing cell) epitopes? The B cell epitope in every human body is the same, so if a virus with a slightly different epitope appears, it will avoid the original antibody in any person infected with the virus. The epitopes of T cells are different. T cell epitopes are presented by MHC molecules encoded by highly polymorphic genes and are located on the surface of infected cells. This means that your MHC is likely to be different from mine, and the viral peptides displayed in it may also be different. So if the epitope of a T cell changes during your infection, it is not important to other people. Their infected cells will show different T cell peptides.
SARS-CoV-2 may continue to produce altered spike proteins, thereby completely circumventing antibody neutralization. In this case, T cells may not be enough to prevent serious diseases, and they may be overwhelmed by so many infected cells. In view of the urgency of the pandemic situation, we are eager to produce vaccines as soon as possible, which resulted in such a situation, which is understandable to a certain extent. Most vaccines currently approved for use in emergency situations are based on spike proteins only. If we want to change the spike protein to adapt to the virus variants, we may enter a never-ending cycle, and we must constantly replace the COVID-19 vaccine on a regular basis.
A better solution is to produce a second-generation new coronavirus vaccine that includes viral proteins other than the spike protein.
The development direction of the second-generation new coronavirus vaccine: give full play to the role of T cells!
Inactivated vaccines and attenuated vaccines that include viral proteins other than spike proteins fall into this category; another solution is to modify the authorized mRNA vaccine to encode other viral proteins!
(source:internet, reference only)