![]() ![]() Interestingly, booster vaccination after a prolonged interval to the first vaccine dose resulted in enhanced antibody responses 13. The latter is promoted by the well-known mechanism of antibody avidity maturation which is enhanced by booster vaccination and with time 12. Even protection from the Omicron variant is achieved to a relatively high degree after three vaccinations 11, likely because this induces high titers of antibodies with increased avidity. Indeed, Wuhan strain-based vaccines that induce high avidity antibodies also protect from severe disease caused by prominent VoCs 3. Nevertheless, it is well documented that some VoCs exhibit clearly higher affinities for ACE2 3, 7, 8, 9, supporting the notion that the above-described affinity type escape is a general phenomenon of SARS-CoV-2.Ĭonsequently, vaccine optimization should aim at inducing higher avidity antibodies, rather than altered epitope specificity as would be required for new serotypes 10. ![]() Differences in assay setups (e.g., plate coating of ACE2 7 versus coating of RBD on sensor chips 3) may lead to different affinities measured in specific cases. Thus, increasing receptor affinity may constitute a new pathway for viruses to escape neutralizing antibodies and may be called affinity escape 6. Indeed, neutralizing antibodies after infection and vaccination have difficulties in competing with RBD-ACE2 binding, suggesting that neutralization is reduced despite that the epitopes of the mutated RBD maintained essentially the same specificity for these antibodies (Fig. This not only causes the well-known increased infectivity but also shifts the virus-receptor equilibrium to the right, i.e., the virus binds more strongly to the ACE2 receptor. While RBD of the Wuhan strain binds ACE2 with an affinity of 2–10 −8 M, RBD with the L452R and E484Q mutations (such as in the Delta and Kappa variants) shows a 4–5 fold higher affinity for the receptor 3. In contrast, we have recently demonstrated that viral strains can escape neutralizing antibodies despite essentially preserved recognition specificity: by ways of increased receptor affinity. Generally, the demonstration of mAbs capable of distinguishing distinct variants is not sufficient to declare new serotypes, as serotypes are defined by polyclonal anti-sera. Thus, the current data do not fully demonstrate the existence of different SARS-CoV-2 serotypes. While this observation suggests development of viral serotypes, it has been difficult to make the reverse observation, i.e., to find or induce sera that neutralize variants with the E484K mutation better than the Wuhan strain 3, 4, 5. For the Beta and Gamma variants of SARS-CoV-2, it has recently been shown that the E484K mutation within the receptor binding domain (RBD) of the spike protein strongly reduces recognition by convalescent sera from individuals after infection with the original Wuhan strain 2, 3. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |