The South African variant B.1.351 / 501Y.V2 of Covid-19: characteristics

The South African variant B.1.351 / 501Y.V2 of Covid-19: characteristics

The characteristics of the South African variant B.1.351 / 501Y.V2 of Covid-19

 

History and discovery of the South African variant B 1.351 / 501Y.V2 of Covid-19

The South African variant B1.351 / 501Y.V2 probably emerged during the first wave of the Covid-19 outbreak in South Africa in the Nelson Mandela Bay metropolitan area in October 2020 and subsequently spread widely to become the predominant variant in the East and West Cape Town provinces in November 2020 (1).

The variant subsequently developed first in Botswana and then in many other countries including England, Scotland, France, Sweden, Switzerland, South Korea last December 2020. (6). It seems that the arrival of the South African strain in England even took place with 8-9 different single introductions (i.e. single different travelers).

The transmission rate of the South African variant is still unknown. However, there was a significant increase in cases and mortality in correspondence with the emergence of the South African variant (1).

The reasons behind the mutations of the South African variant B1.351 / 501Y.V2 of Covid-19

How did the South African variant of Covid-19 come about? And how are the variants of Covid-19 created in general? One of the hypotheses that has recently been formulated is that an evolution of the virus takes place within the host in association with a prolonged infection (7).

In this regard, the case of a 45-year-old man who was infected with the classic variant of Coronavirus was reported. Since he was immunocompromised (9), the infection lasted a very long time and on the 75th and 128th day of infection, two mutations appeared, E484K and N501Y, respectively (7).

This is only one of the possible mechanisms, since many other less relevant mutations have also been found in the South African variant. It has also been proposed that mutations that do not concern the attachment sites of the Spike protein are necessary, from an evolutionary point of view, almost to compensate for the most important mutations, to maintain better structural stability of the entire Spike protein. (8)

 

The structure of the South African variant B 1.351 / 501Y.V2.

The modified regions of the South African variant of Covid-19

The South African variant of Covid-19 contains some mutations, (8), including three peculiar mutations on the Spike protein (see notes):

  • K417N (3)
  • E484K (4)
  • N501Y (5) This mutation is also present in the English variant B.1.1.7

 

The resistance of the South African variant B.1.351 / 501Y.V2 of Covid-19 to antibody neutralization

Variant B.1.351 has an increased resistance to neutralization by most monoclonal antibodies to the terminal domain of the Spike protein (NTD) and a high resistance to a fair number of monoclonal antibodies to the receptor-binding domain (RBD) (2).

Efficacy of monoclonal antibodies on the South African variant B.1.351 / 501Y.V2 of Covid-19

The South African variant is able to completely eliminate the effectiveness of the following monoclonal antibodies:

  • 910-30, mediated by the K417N mutation
  • 2-15, mediated by the E484K mutation
  • LY-CoV555 (bamlanivimab), mediated by the E484K mutation
  • C121, mediated by the E484K mutation
  • REGN10933 (casirivimab), mediated by the E484K and K417N mutations
  • 5-24
  • 4-8
  • 2-17
  • 4-19
  • 4A8

However, the effectiveness of:

  • 2-7
  • REGN10987 (imdevimab)
  • C135
  • S309
  • 5-17

Efficacy of hyperimmune plasma on the South African variant B.1.351 / 501Y.V2 of Covid-19

The South African variant B.1.351 has a very high resistance, on average between 11 and 33 times, to polyclonal antibodies present in the hyperimmune plasma of subjects previously immunized by Covid-19 in its traditional variants. The study was conducted on plasma from 20 subjects with documented infection during the spring of 2020. (2)

Efficacy of vaccines on the South African variant B.1.351 / 501Y.V2 of Covid-19

Studies disagree on this. The resistance of the specific type of vaccine to the South African variant may also depend on the vaccine itself.

 

Efficacy of Pfizer vaccine on the South African variant B.1.351 / 501Y.V2 of Covid-19

In the first study (2) that we report, serum from patients vaccinated with Pfizer’s vaccine was tested. In this study, 10 sera were collected from people who had received Pfizer’s vaccine, during the first trials carried out. This study shows that the South African variant has a very high resistance, on average between 6 times, to the polyclonal antibodies present in the vaccine serum of subjects vaccinated for Covid-19 for Pfizer’s vaccine (2).

Another study, on the other hand, collected sera from 20 patients who had previously been vaccinated with Pfizer’s vaccine and tested them against the South African variant of the Coronavirus, highlighting an equivalent neutralizing efficacy against the mutated virus (10).

Efficacy of the Moderna vaccine on the South African variant B.1.351 / 501Y.V2 of Covid-19

In the study we report, the serum of patients vaccinated with Moderna’s vaccine was tested. In this study, 12 sera were collected from people who had received Moderna’s vaccine, during the first trials carried out. This study shows that the South African variant has a very high resistance, on average 8 times, to polyclonal antibodies present in the vaccine serum of subjects vaccinated for Covid-19 for the Moderna vaccine (2).

In another study, the reduction in the effectiveness of the antibodies produced by Moderna’s vaccine was confirmed by as much as 6 times (12)

 

Efficacy of the Indian Covaxin vaccine on the South African variant B.1.351 / 501Y.V2 of Covid-19

No data are yet available for Covaxin vaccine.

 

How to identify the presence of the South African variant in the population?

A group of scientists declared, in a study not yet reviewed, that they were able to develop a set of different primers, one for each variant of Covid-19, in this case, in addition to the South African one, also for the English variant and the Brazilian one (11).

This will allow you to perform a second level diagnostic test after the positivity evaluation test. In the second test, to be performed only on positive patients, it will be possible to identify the type of variant in place, whether the traditional one or the emerging ones.

The possibility of identifying the South African variant in the subject will also allow choosing the most appropriate treatment, for example opting for monoclonal antibodies rather than hyperimmune plasma, which is ineffective on the South African variant and could instead be destined with greater benefit to subjects carrying other variants.

 

Med4Care Marco De Nardin

Dr. Marco De Nardin

 

Sources and notes:
  1. Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa
  2. Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization
  3. This mutation consists of exactly a lysine instead of an asparagine in position 417
  4. Glutamic acid instead of a lysine in position 484
  5. This mutation consists of exactly one asparagine instead of tyrosine at position 501
  6. Introduction of the South African SARS-CoV-2 variant 501Y.V2 into the UK
  7. Choi B., Choudhary M.C., Regan J. Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host. 
  8. Tegally H., Wilkinson E., Giovanetti M., et al. Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa
  9. For the presence of an anti-phospholipid antibody syndrome

 

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