Do the variants call into question the efficacy of the vaccines?
Text updated on 2021-01-14
Most of the vaccines developed so far involve the production of antibodies to the Spike protein. Spike is a needle-shaped coronavirus protein and plays a very important role in the infection of human cells. It binds to certain receptors in human cells, called ACE2, and then functions as a key that opens a door by allowing the coronavirus to enter the cells.
What's reassuring is that the vaccines elicit a fairly broad antibody response, directed against different regions of the Spike protein. Therefore, small local changes are unlikely to render all the antibodies in a vaccine ineffective. But this needs to be verified experimentally for coronavirus variants with the many mutations that affect the Spike protein. Since January 2021, studies have been underway to determine whether the new common variants of SARS-CoV-2 will decrease vaccine efficacy. Note that RNA vaccines (Pfizer BioNTech and ModeRNA) can be updated quickly to work on new variants: it takes a few weeks to create a new RNA vaccine against SARS-CoV-2.
A study that evaluates the recognition of the Spike protein from SARS-CoV-2 based on mutations in the antibodies contained in the serum of 17 people with COVID-19 recovering in the United States. This analysis involved patients naturally infected with the coronavirus, who did not receive the vaccine, to determine whether the antibodies they developed as a result of the infection (and which would likely be similar if vaccinated) were able to elicit an immune response to other variants of the virus. Patients were followed longitudinally and sera were collected at least twice for each patient between 15 and 121 days after the onset of symptoms. Several Spike protein mutations were tested and the results show that there is enormous variability between the different patient sera and also variability over time for the same patient. Some sera are not affected by any of the mutations, while others are. Among the mutations, some seem to affect antibody recognition more than others. Notably in 11 of the 17 patients for whom the serum was collected approximately 30 days after the onset of symptoms, the authors report that mutations at the E484 site, mutated into the 501Y.V2 variant discovered in South Africa, reduced antibody recognition in 9 of the 11 patients. On the other hand, the mutation at the N501 site, like that observed in the British variant VoC 202012/01, had no significant effect on antibody recognition.Greaney, A. J., Loes, A. N., Crawford, K. H., Starr, T. N., Malone, K. D., Chu, H. Y., & Bloom, J. D. (2021). Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies. bioRxiv, 2020-12.
In this study, the authors tested the immune response on two forms of coronavirus: an initial form taken from a patient and a mutated form obtained after culture for 90 days in the presence of a patient's plasma (part of the blood). The plasma immune response of 20 convalescent patients was tested before and after mutation. In vitro, the results show a high variability in the immune response of different plasmas against the non-mutated form of SARS-CoV-2. At the end of 90 days, the virus had acquired three mutations on the Spike protein, including the E484K mutation present on the South African variant 501v2. The authors showed that mutations in the virus could affect the immune response and that it was at least half as effective against the mutated form as against the non-mutated form, with however a great variability between the different plasmas. The infectivity of the mutated and non-mutated forms appeared to be comparable.Andreano, E., Piccini, G., Licastro, D., Casalino, L., Johnson, N. V., Paciello, I., ... & Rappuoli, R. (2020). SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 Convalescent plasma. bioRxiv.
This study showed that the 501Y.V2 variant, detected for the first time in South Africa and containing 9 mutations in the Spike protein, (L18F, D80A, D215G, Δ242-244, and R246I, K417N, E484K, and N501Y) seems to escape the antibody immune response: they reduce the neutralization of the virus by antibodies. In vitro, these mutations prevent the binding of three types of antibodies. In addition, the antibody binding capacity of the antibodies derived from the plasma of 44 persons previously infected with SARS-CoV-2 and convalescent is 4 times lower for the 501Y.V2 variant than for the non-mutant lineage.Wibmer, C. K., Ayres, F., Hermanus, T., Madzivhandila, M., Kgagudi, P., Lambson, B. E., ... & Moore, P. L. (2021). SARS-CoV-2 501Y. V2 escapes neutralization by South African COVID-19 plasma donor. BioRxiv.
In vitro study which shows that the plasma neutralization activity of 6 convalescent persons previously infected with SARS-CoV-2 (lineage SARS-CoV-2 D614G) and convalescent is reduced for the 501Y.V2 variant compared to the non-mutant form of SARS-CoV-2.Cele, S., Gazy, I., Jackson, L., Hwa, S. H., Tegally, H., Lustig, G., ... & Sigal, A. (2021). Escape of SARS-CoV-2 501Y. V2 variants from neutralization by convalescent plasma. medRxiv.
In this study, serum was collected from 20 people vaccinated with two doses of Pfizer vaccine. The authors then studied the neutralizing activity of these sera against three types of mutations in SARS-CoV-2 : (1) N501Y present on the UK and South African variant, (2) 69/70-deletion + N501Y + D614G present on the UK variant and (3) E484K + N501Y + D614G present on the South African variant. The neutralizing activity of the 20 sera was 0.81 to 1.46 times the neutralizing activity against the non-mutated virus, indicating that after two doses of Pfizer vaccine individuals are well immunized against the variants that were tested.Xie, X., Liu, Y., Liu, J., Zhang, X., Zou, J., Fontes-Garfias, C. R., ... & Shi, P. Y. (2021). Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nature Medicine, 1-2.