The key question in vaccine development would be, under the selective pressure of the polyclonal immune response of vaccinated people, if the virus evolves to escape from the immunity? and if it is effective against virus mutations or not?
A group from Fondazione Toscana Life Sciences, Siena, Italy etc. has reported the results of co-culture of cells and virus with using neutralize antibodies (polyclonal) obtained from the plasma of convalescent patients from the new coronavirus (COVID-19).
https://pubmed.ncbi.nlm.nih.gov/33398278/
In this experiment, VERO E6 cells and SARS-CoV-2 were co-cultured for 100 days (14 passages over) using neutralizing antibodies with the highest neutralizing titer among 20 convalescent patients, to investigate the relationship between changes in the titer of neutralize antibodies and genetic mutations that occurred in viruses. In this experiment, the following mutations have occurred in the NTD and RBD of the S protein, and it is shown that the titer of the neutralize antibody decreases with it.
- deletion of the phenylalanine in position 140 (F140) on the S-protein NTD N3 loop.
- glutamic acid in position 484 of the RBD was substituted with a lysine (E484K).
- 11-amino-acid insertion between Y248 and L249 in the NTD N5 loop (248aKTRNKSTSRRE248k).
The results of this experiment show that virus can evolve to escape from the selective pressure of even the highest titer neutralize antibodies. So, it is recommended to use cocktail antibodies for treatment. In addition, it suggests the need to develop a second-generation vaccine that can accommodate mutations.
