SARS-Cov-2 infected patients appear to be protected for a minimum of eight months against new infection. However, both Brazil and South Africa have reported inferior protection. This is probably linked to the appearance of viral variants with a high prevalence in these countries (P1 and B.1.351, respectively).
The two variants mentioned are part of the so-called VOCs, variants of concern, with mutations in regions of the viral envelope protein known as “spicule”. It interacts with the ACE2 receptor, the entry gate of the virus to cells. Therefore, these variants may no longer be recognized by neutralizing antibodies generated after the administration of vaccines or during a previous infection.
The vaccines that are being used contain only the viral surface protein (spicule) and their sequence is that described in January 2020 (Wuhan strain). In some of these vaccines, the three-dimensional structure of the protein has been stabilized in a conformation that facilitates the generation of neutralizing antibodies that prevent cell infection.
There are several strategies that allow evaluating the importance of these variants in the evasion of immunological memory achieved with vaccination or infection.
Studies carried out in the laboratory have shown that the antibodies present in the sera of convalescent or vaccinated patients are capable of hindering the infection of susceptible cell lines by these viral variants. This protection against cell infection is called neutralization, and only some antibodies that bind to the spike have this property.
The size of the area of interaction with the ACE2 receptor causes that some viral variants are better neutralized by sera from some patients and worse by those of others. Unfortunately, the neutralization of some of these variants requires a higher concentration of antibodies, so this neutralization capacity can be lost over time.
It has not yet been possible to define an antibody concentration threshold that allows predicting whether or not there is protection. This partial resistance to neutralization is more pronounced in the variants in which amino acid 484 of the spike has mutated, as occurs in the P1 and B.1.351 variants.
The greater resistance to neutralization of B.1.351 demonstrates the participation of other regions present in the spicule. Fortunately, changes in position 501 do not significantly alter the ability to neutralize the virus by antibodies present in the serum of vaccinated patients. This mutation is present in variant B.1.1.7, first identified in the United Kingdom and currently the majority in Spain and Europe.
Clinical trials conducted in populations where variants partially resistant to neutralization in vitro
The South African clinical trial of the AstraZeneca vaccine showed that the vaccine did not protect against mild or moderate infection. However, other licensed vaccines, such as the Janssen adenovirus vaccine, mRNA vaccines and a vaccine in which the spicule is administered in nanoparticle form, do protect against infection by this variant, although a decrease in the effectiveness.
Vaccination-generated memory T lymphocytes, which recognize spike peptides preserved in the different variants, may also play an important role in this protection.
The results obtained in real life in countries that have achieved high vaccination coverage have shown that the approved vaccines have enormous efficacy against the B.1.1.7 variant, the majority in Israel and the United Kingdom. Furthermore, there is less transmission due to asymptomatic patients.
Some vaccines could protect from infection by variants partially resistant to neutralization in vitro (B.1.351) even better than infection by previously circulating viruses. It has been suggested that the changes in the three-dimensional structure of the spike present in some of these vaccines may generate a broader and more diverse response, thereby reducing the resistance to neutralization of viruses that have mutated amino acid 484.
This is coupled with the high concentration of neutralizing antibodies achieved after vaccination, which is even higher in patients who had previously been ill with covid-19. Furthermore, the sera of these patients, convalescent and vaccinated, are capable of neutralizing viral variants that were partially resistant before vaccination.
Currently, clinical trials are being developed in which vaccines (adenovirus and mRNA) are alternated or a new dose of the spike is provided with the mutations present in the B.1.351 variant.
It is essential to establish surveillance and evaluation strategies that allow the precise analysis of the efficacy of the different vaccine strategies in the prevention of symptomatic disease or the capacity to transmit variants of concern or interest that have already been identified or that may appear in the future.
The experimental and observational results are encouraging, given that the vaccines in use appear to provide protection even in the context of the emergence of new variants.