Do the variants call into question the efficacy of the vaccines?
Text updated on 2021-08-31
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 is reassuring is that the vaccines elicit a fairly broad antibody response, directed against different regions of the Spike protein. It is therefore unlikely that small local changes will render all the antibodies in a vaccine ineffective. Since January 2021, several variants have been described (see question Which variants of the coronavirus SARS-CoV-2 have attracted attention?). Several studies have been carried out to determine whether the most common variants of SARS-CoV-2 decrease the effectiveness of vaccines. Immunity induced by RNA vaccines (Pfizer and Moderna) (see question What are the different types of vaccines against COVID-19 ?) appears to be effective in protecting against the variants described to date. Immunity induced by the AstraZeneca vaccine appears to be more or less effective depending on the variants.
It should be noted that RNA vaccines can be updated quickly to work on new variants: it takes a few weeks to create a new RNA vaccine against SARS-CoV-2.
For a summary table of vaccine efficacy according to variants, see Table 1 of http://www.healthdata.org/covid/covid-19-vaccine-efficacy-summary.
The Pfizer and Moderna RNA vaccines protect people who have not been previously infected with the coronavirus SARS-CoV-2 from the Delta B. 1.617. 2 variant. The study did not analyse previously infected individuals who were vaccinated with a single dose.Bernal, J. L., Andrews, N., Gower, C., Gallagher, E., Simmons, R., Thelwall, S., ... & Ramsay, M. (2021). Effectiveness of COVID-19 vaccines against the B. 1.617. 2 variant. medRxiv.
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.
Study showing that the effectiveness of the AstraZeneca vaccine against the B.1.351 Beta variant detected in South Africa is 10.4%.Madhi, S. A., Baillie, V., Cutland, C. L., Voysey, M., Koen, A. L., Fairlie, L., ... & Izu, A. (2021). Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B. 1.351 variant. New England Journal of Medicine, 384(20), 1885-1898.
The efficacy of the Pfizer vaccine (14 days after the second dose) is 89.5% against the B.1.1.7 Alpha variant and 75.0% for the B.1.351 Beta variant. The efficacy of the RNA vaccine against severe forms of COVID-19 is very high for both variants: 97.4%.Abu-Raddad, L. J., Chemaitelly, H., & Butt, A. A. (2021). Effectiveness of the BNT162b2 Covid-19 Vaccine against the B. 1.1. 7 and B. 1.351 Variants. New England Journal of Medicine.
Study carried out on 12,675 people who were vaccinated with the Pfizer RNA vaccine or the AstraZeneca vaccine. The results show that after one dose of vaccine, the efficacy is 51.1% for the B.1.1.7 Alpha variant, detected in Great Britain, and 33.5% for the B.1.617.2 Delta variant, detected in India, with similar results for both vaccines. After 2 doses of Pfizer vaccine, the efficacy against the B.1.1.7 variant is 93.4% and against the B.1.617.2 variant 87.9%. After 2 doses of the Astrazeneca vaccine, the efficacy against the B.1.1.7 variant was 66.1% and against the B.1.617.2 variant, 59.8%.Bernal, J. L., Andrews, N., Gower, C., Gallagher, E., Simmons, R., Thelwall, S., ... & Ramsay, M. (2021). Effectiveness of COVID-19 vaccines against the B. 1.617. 2 variant. medRxiv.
Study of 324,033 people vaccinated with an RNA vaccine (Pfizer-BioNTech and Moderna) which shows that the vaccine is 60% effective against symptomatic forms of COVID-1920 days after the first injection. Seven days after the second injection, the efficacy is 91%. The efficacy against severe forms of COVID-19 is 62%, 20 days after the first injection and 98%, 7 days after the second injection. The efficacy of RNA vaccines is also high against the B.1.351 so-called Beta (detected in South Africa) and P.1 so-called Gamma (detected in Brazil) variants, which contain the E484 mutation.Chung, H., He, S., Nasreen, S., Sundaram, M., Buchan, S., Wilson, S., ... & Kwong, J. C. (2021). Effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes in Ontario, Canada.