Do new coronavirus viruses make the vaccine less effective? Since the gradual discovery of at least three new “worrying” (“concern” or VOC) variants, this question has struck everyone’s heart: one in the South of England – the “English version” – more correctly. It is said to be B.1.1.7 and is now found in 57 countries until 20 January; Second in South Africa (501Y.V2 or B. 1.351); And one last in Brazil, say P1, is found in three countries (live surveillance of viral lines on the SARS-CoV-2 lineage). All three independently acquired a common N501 mutation, indicating that it had a special role in the resurgence of the epidemic in these three countries. So far, three pre-publication studies (not peer reviewed) show that the English version of the virus does not have the ability to avoid the effectiveness of RNA in the modern “and Pfizer lab”. In other words, mutations that alter it, including N501, do not sufficiently modify its structure to evade specific antibodies generated by vaccination. But things are too small for the South African and Brazilian variants.

Two worrying forms

Two studies – still in prepolubation and should therefore be taken with caution – suggest that the effectiveness of the immune response elicited through vaccines is reduced compared with the other two variants. Indeed, the latter are at least two other disturbing mutations not in the English version: E484 and K417. All three mutations are common with N501 – it is that they modify a very specific region of the spike proteins that make up the crown of the virus. Namely the so-called “RBD” receptor binding domain, which acts as a hook to bind the ACE2 receptor located on cells susceptible to infection. Because of this role of the anchoring point of the virus in our cells, RBD of the spike is an essential area for the effectiveness of a vaccine built on the initial spike model. If the protein structure changes too much, specific neutralizing antibodies generated from a vaccine model will be less likely to be effective (see diagram below).

In BiorxivOn January 15, 2021, a team at Rockefeller University in New York studied the immune response to the South African variant in 20 patients who received either the Modern or Pfizer vaccine. Eight weeks after their second dose of vaccine, all had to highly neutralize antibody levels and immune cell activity to cure patients. “However, activity E484K or N501Y or K417N / E484K / N501Y combination against SARS-CoV-2 variants was reduced by a small but significant margin.”.

Zoom to the RBD, receptor binding domain, a small portion of the S protein of the coronavirus (an overview of S at bottom right) that connects it to the ACE2 receptor present on our cells. Red arrows indicate modifications in the structure of the spike protein due to the various mutations of interest described (E484, N501, etc.). Colored coils (C666, C663, etc.) represent fingerprints of various specific antibodies produced. Credit: Xijun Wang et al, Biorexive

The authors of the study performed a comparative analysis of the structures of various antibodies induced by vaccination or natural infection.

Are there less effective vaccines? Since the gradual discovery of at least three new “worrying” (“concern” or VOC) variants, this question has struck everyone’s heart: one in the South of England – the “English version” – more correctly. It is said to be B.1.1.7 and is now found in 57 countries until 20 January; Second in South Africa (501Y.V2 or B. 1.351); And one last in Brazil, say P1, is found in three countries (live surveillance of viral lines on the SARS-CoV-2 lineage). All three independently acquired a common N501 mutation, indicating that it had a special role in the resurgence of the epidemic in these three countries. So far, three pre-publication studies (not peer reviewed) show that the English version of the virus does not have the ability to avoid the effectiveness of RNA in the modern “and Pfizer lab”. In other words, the symptoms that change it, including N501, do not sufficiently modify its structure to avoid specific antibodies generated by vaccination. But things are too small for the South African and Brazilian variants.

Two worrying forms

Two studies – still in prepolubation and should therefore be taken with caution – suggest that the effectiveness of the immune response elicited through vaccines is reduced compared with the other two variants. Indeed, the latter are at least two other disturbing mutations not in the English version: E484 and K417. All three mutations are common with N501 – it is that they modify a very specific region of the spike proteins that make up the crown of the virus. Namely the so-called “RBD” receptor binding domain, which acts as a hook to bind the ACE2 receptor located on cells susceptible to infection. Because of this role of the anchoring point of the virus in our cells, RBD of the spike is an essential area for the effectiveness of a vaccine built on the initial spike model. If the protein structure changes too much, specific neutralizing antibodies generated from a vaccine model will be less likely to be effective (see diagram below).

In BiorxivOn January 15, 2021, a team at Rockefeller University in New York studied the immune response to the South African variant in 20 patients who received either the Modern or Pfizer vaccine. Eight weeks after their second dose of vaccine, all had to highly neutralize antibody levels and immune cell activity to cure patients. “However, activity E484K or N501Y or K417N / E484K / N501Y combination against SARS-CoV-2 variants was reduced by a small but significant margin.”.

Zoom to the RBD, receptor binding domain, a small portion of the S protein of the coronavirus (an overview of S at bottom right) that connects it to the ACE2 receptor present on our cells. Red arrows indicate modifications in the structure of the spike protein due to the various mutations of interest described (E484, N501, etc.). Colored coils (C666, C663, etc.) represent fingerprints of various specific antibodies produced. Credit: Xijun Wang et al, Biorexive

The study’s authors performed a comparative analysis of the structures of various antibodies induced by a vaccine or a natural infection, showing that they were very similar and effectively neutralizing SARS-CoV-2. On the other hand, “Neutralization by 14 of the 17 strongest antibodies tested was reduced or suppressed by K417N, E484K or N501Y mutations”, Rewrite the authors.

Towards an update to the vaccine strain

Another pre-publication in Biorxiv The South African team also confirms these first observations published on 18 January. But you have to be careful. Researchers did not conduct their experiments on those vaccinated in this case, but in laboratory-grown monoclonal antibodies or the serum of Convents in which their antibodies are found. They show here that 501Y.V2 presents the viral line “A complete migration to three classes of clinically relevant monoclonal antibodies”, And “A significant or complete leak of neutralizing antibodies into the plasma of antibodies”.

Here, I have replicated the data from the preprint to make the effect size a bit more clear. Each line is a sera tested by an individual with the wildpea virus on the left and the 501Y.V2 variant virus on the right. Note the log y axis (as is normal with this type of data). 2/10 pic.twitter.com/8OwKYErTZQ

– Trevor Bedford (@trvrb) 20 January 2021

The image, taken by American professor Trevor Bedford, an expert in genomics and epidemiology of infectious diseases, represents a decline in the rate of immunity of immunity between the widespread form of the virus (left) and the South African version 501Y. .V2 (right). “Each line represents the serum of a person tested against the virus on the left and the 501Y.V2 variant on the right. If these results are confirmed by other studies, I think, compared to seasonal flu, We need to consider the manufacturing schedule and regulatory steps to update the ‘in-strain’ vaccine used., Trevor Bedford further explains. In other words, laboratories will need to update their vaccines, at one time or another, as with influenza every year. Now it has to be determined how often it will be necessary: ​​every year? every two years ? Every five years?

On December 22, 2020, Director of the Genetics Institute at University College London and expert on virus genomics Prof. Explained to François Ballox. Science and future : “Before we saw the emergence of this line (B.1.1.7), it was clear that regular redefining of sequences in vaccine should be considered. This may be faster than thought.”

“501Y.V2 is still largely confined to South Africa, Judge Trevor Bedford, But it (that or other antigen-derived form) may spread more widely in the coming months. I anticipate this possible update of “stress” for the fall of 2021. That being said, I will get vaccinated as soon as possible. We now have an amazing vaccine that works against the circulating virus. And if this becomes necessary, this emerging situation can be addressed with the upcoming vaccine update. “

In fact, modern and Pfizer vaccines are still very effective against the vast majority of viral lines in circulation. It should be said that they start from high because an efficiency of 94% –95% gives a small margin before a vaccine is less relevant in this efficiency. Two preliminary studies conducted online on 20 January have confirmed their effectiveness against the English version. At first, A British and Dutch team evaluated the effectiveness of the vaccine by comparing the English version of plasma in the laboratory of 36 patients cured after suffering from severe or minor forms of Kovid-19. “Most Samples” Was able to “Neutralization” Even if the variant “Power” Neutrality was reduced in three of the samples. In a second study, the BioNotech / Pfizer team of researchers arrive at a similar conclusion, comparing the effects of plasma from 16 participants in the English version and its clinical trials on the original Wuhan virus. They conclude that both have an “equivalent” neutralization capability and are thus thought to be “unlikely” that the English variant “escapes the defense” of their vaccine. Where appropriate, they state that the “flexibility” of this messenger RNA vaccine technique will allow the vaccine to adapt to a new strain of the virus.

Meanwhile, three other variants have been mentioned in recent weeks, such as Unrecognized: In Japan, Germany, and California where the outbreak of the epidemic may be caused by an L425R variant that appears to be “within a few weeks”. Tax will be levied in 25% of cases.