Viruses change permanently due to the appearance of mutations. Therefore, the appearance of variants in SARS-CoV-2 was expected. More than 4,000 variations have been described in the “S” protein ( spike ) that the virus uses to infect cells after binding to the human ACE2 protein. Mutations can modify human-to-human transmission, the clinical course of infection, and its recognition by antibodies and antiviral T lymphocytes. The D614G variant is an example of this, where the change of the aspartic amino acid (D) for Glycine (G) at amino acid 614 has made this viral lineage (called B.1) have replaced the previous ones.
Viral variants have also been identified that have mutated the amino acids present in the region of the protein “S” that interacts with ACE2 (domain of binding to its receptor known in English as “RBD”). This ability to harbor mutations in this region without decreasing its infectivity is called plasticity and has been linked to the success of the virus in being transmitted between humans, cats or minks. These variants accumulate other mutations / deletions that can increase their transmission capacity.
Approved RNA vaccines contain only the genetic information for the “S” protein and therefore only antibodies and T lymphocytes are generated against it. The sequence of the vaccine protein “S” is, with certain modifications, identical to that which existed at the beginning of the pandemic (Wuhan strain), and therefore different from the sequence of the protein S of currently circulating viruses . This has not prevented vaccines from being very effective: they prevent more than 95% of infections in clinical trials. This appears to be due to the fact that the dominant mutations (D614G) do not fall in the RBD region, which is recognized by neutralizing antibodies that block infection.
The T lymphocytes generated with the RNA vaccines will recognize peptides (fragments) of that vaccine “S” protein. These fragments can come from any region of the “S” protein, so it is reasonable to think that the vaccination will generate many memory T cells that recognize identical peptides of the “S” protein between the vaccine and the circulating viruses to which the patient vaccinated can be exposed. These T lymphocytes can hinder the proliferation of the virus by different mechanisms, among which the destruction of infected cells stands out.
Antibodies secreted by plasma cells useful to prevent virus infection of cells primarily recognize the RBD region. Circulating viral variants have been described in which amino acids in this area are different from those contained in the vaccine, such as those present in variant B.1.1.7 (England) or 501-V2 (South Africa). These viral variants contain a maximum of two mutations in this RBD region. Antibodies interact with a minimum of 10 amino acids of the S protein. Thus, a change in one amino acid may decrease the binding capacity, but not completely prevent it.
In addition, the RBD region has more than 100 amino acids that can be recognized by antibodies, so a change in one amino acid can make it difficult for some, but not all, neutralizing antibodies generated with the vaccine to bind. Therefore, it was expected that variant B.1.1.7 does not have a greater capacity to reinfect patients already cured.
Vaccines, a ‘challenge’ for the virus
The jump to the human species of the SARS-CoV-2 virus has been so recent that practically the entire population can be infected by not having previous immunity. However, vaccination will change the situation and it cannot be ruled out that variants are selected that escape recognition by the antiviral effector mechanisms awakened with the vaccine.
In fact, viral variants have already been described in immunosuppressed patients that have emerged and have been selected after the therapeutic administration of sera from patients who had already cleared the infection.
For this reason, it is essential to continue with all non-pharmacological measures aimed at reducing the number of cases, and thus the probability of selecting resistant viral variants.
Furthermore, epidemiological and genetic monitoring of the viral variants responsible for infections in vaccinated, reinfected or resistant patients to treatment with antibodies against SARS-CoV-2 is essential. In these situations, it will be necessary to take extreme measures of isolation and follow-up of contacts.
Vaccines can be updated
The emergence of viral variants that infect a proportion of vaccinated patients does not have to lead to a pandemic of the dimension we now face if there is access to vaccines worldwide. RNA vaccines will allow, where appropriate, the design and production of new versions that incorporate the “S” protein of the new viral variants that could cause infections in vaccinated individuals in a short space of time.
In addition, vaccines are being developed that contain more viral proteins and, therefore, are less likely to generate variants that escape the immune response generated with these vaccines.
Pedro Aparicio Alonso, Professor of Immunology, University of Murcia
This article was originally published on The Conversation. Read the original.
