In 1960 Thomas Francis in his article “On the doctrine of ‘ancestral’ antigenic sin” described the blockage of the immune system and its inability to cope with an infection due to an older infection with a similar germ. How can this happen? The Professors of the Medical School of the National and Kapodistrian University of Athens, Gikas Majorkinis and Thanos Dimopoulos (Rector of EKPA), report that after an infection the immune system creates memory against the germ that it encountered in the memory cells so that in the next “meeting” it is ready to deal with the germ faster and more effectively. We take advantage of this property with vaccines, we create a memory in the immune system so that when the body is infected it can fight the germ faster and more effectively.
Francis, however, described what can happen when another, related but not identical germ infects the body. In this case it is possible due to the relative similarity of the new microbe not to activate the mechanism of initial recognition of microbes (virgin cells) but to activate the memory mechanism (memory cells) that will produce antibodies against the microbe that initially infected the organism. If the antibodies produced have a good neutralizing effect against the new germ then it will lead to faster and more effective treatment of the infection. However, if the antibodies produced are not as effective against the new bacterium, then the immune system is blocked, as the primary microbial recognition procedures will not proceed well enough. At the same time, immune memory produces these antibodies that do not effectively kill the new germ, creating a vicious cycle.
The phenomenon of antigenic “ancestral” sin has been studied for several years in influenza. Researchers have shown that previous exposure to specific strains of influenza virus resulted in cross-protection through immune memory against the 2009 pandemic strains (H1N1). However, the negative interaction has also been described in different conditions where an older infection with other types of influenza virus led to a weakened immune response.
The question, then, in relation to SARS-CoV-2 is first of all whether the earlier infections with the widely circulating coronaviruses (common cold) create conditions of antigenic “ancestral” sin. Secondly, if the memory of the common cold viruses is recalled after infection with SARS-CoV-2, then does it work protectively or negatively?
Some related studies show that older common cold virus infections help to improve the outcome of the infection due to the production of antibodies that cross-react with SARS-CoV-2. Another study showed that infection with SARS-CoV-2 led to an increase in antibodies that are specific to other coronaviruses without these antibodies having a significant neutralizing effect on SARS-CoV-2. These could be signs of a negative interaction, however there are studies showing that people who have had recent signs of another coronavirus infection have recovered faster than SARS-CoV-2.
A key question, however, concerns the development of up-to-date vaccines, whether antigenic “ancestral” sin could adversely affect the development of immune memory through vaccination. The data are quite positive as it appears that vaccination with mRNA vaccines leads to a much smaller increase in antibodies produced by memory cells against other coronaviruses. In any case, the immunologists emphasize that the vaccines can be designed in such a way as to avoid blockage through this mechanism, so there is no particular problem if updated vaccines are needed against mutant strains of SARS-CoV-2.
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