Friday, January 22

Pfizer’s vaccine works against one of the most feared mutations of the coronavirus


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Since December, laboratories around the world have been racing to find out if two new variants of coronavirus, one detected in South Africa and called 501Y.V2, and another found in the United Kingdom and called B.1.1.7, can be more elusive for vaccines that are being administered. This possibility is especially worrying because there are indications that the two variants are more contagious, up to 50% in the case of the British.

“Many of us are working hard to understand these variants. AND the million dollar question is how important they will be for the effectiveness of the vaccines that are being administered now, “he said to” Nature.com» Jeremy Luban, a virologist at the University of Massachusetts.

This Friday, scientists from the University of Texas (USA), who work for Pfizer, have published important conclusions about the effectiveness of the new vaccines. In a Article very brief, not yet peer-reviewed, the researchers say that the N501Y mutation, present in both the British and South African variants, does not decrease the activity of antibodies generated by the vaccine from Pfizer and BioNTech. However, these results do not evaluate the possible effect of the other dozens of mutations present in the two variants.

“This is good news, mainly because it is not bad news,” he said. Stephen Evans, Professor of Pharmaco-epidemiology at the London School of Hygiene and Tropical Medicine, for Science Media Center. “If the result had been the opposite (…) it would have been very worrying. So this is a good sign, but does not yet give us complete confidence that the Pfizer vaccine, or others, will definitely be protective. We need to verify this in clinical trials, and the data should be available in the next few weeks. ‘

The importance of N501Y

The study published today focuses on the N501Y mutation, a change that appears in the protein S of the coronavirus. This S protein is a “hook” with which the virus recognizes human cells and forces them to enter, after binding to the human ACE2 receptor. Well, several studies have shown that N501Y increases the transmissibility of SARS-CoV-2 because it increases the degree of affinity of protein S for the ACE2 molecule.

The variant has 23 mutations.  In the image, 8 of those that affect protein S (rod-shaped), and with which the virus recognizes human cells
The variant has 23 mutations. In the image, 8 of those that affect protein S (rod-shaped), and with which the virus recognizes human cells – @ ceronlab / @ raticosdefutbol / Julián Cerón Madrigal

Furthermore, as this mutation introduces changes in protein S, which is the target of the Pfizer or Moderna vaccines, it is feared that this transformation may decrease the efficacy of the antibodies generated by the vaccine, because they are directed to the ‘original protein S’ », Not a carrier of the mutation.

The conclusions published today have been obtained by verifying the degree of protection conferred by antibodies to virus infection in cell cultures. These antibodies were obtained from blood samples from vaccinated people with Pfizer / BioNTech drug.

The results are added to a study carried out by the same team, and published on December 22, in which it was concluded that the N501Y mutation does not drastically affect the neutralization capacity of the antibodies present in the serum of people recovered from a COVID-19 infection.

“Next week we will have much more information,” he commented on “Nature.com” Vineet Menachery, a virologist at the University of Texas and co-author of the study published today. In addition, in a matter of weeks, they hope to be able to study the transmissibility of viruses carrying the N501Y mutation in hamsters, which will be key to determining whether the 501Y.V2 (South African) and B.1.1.7 (British) variants are indeed more contagious.

Other mutations are missing

However, the research published today has an important weak point: that the effect on antibodies of one mutation, N501Y, has only been evaluated when in the two variants there are more mutations that could be important.

In fact, variant B.1.1.7 has 23 mutations, eight of which are in protein S, (the hook with which the virus recognizes human cells to attack them, after recognizing the human ACE2 receptor). On the other hand, variant 501Y.V2 has 21 mutations, nine of them in that molecule.

“A limitation of the study is that the mutation was studied separately,” he explained Deborah Dunn-Walters, Professor of Immunology at the University of Surrey. “And the truth is that the evidence, such as structural modeling, indicates that mutations could interact with each other and affect the structure of antigens (the part of the virus recognized by the immune system). Therefore, they should be analyzed together.

A more worrying change

On the other hand, Trevor Bedford, an epidemiologist at the Fred Hutchinson Research Center and a professor at the University of Washington (USA), has commented that “it is necessary to examine the effect of all mutations” and that there is a much more disturbing mutation: “N501Y is not the mutation we have to worry about in terms of neutralization”, said on Twitter. “The focus is now on the mutation E484K, owned by variant 501Y.V2 (South African) ‘.

From recent studies, ( here and here), in which it is analyzed how antibodies make it difficult for the virus to enter cells, have shown that this E484K mutation helps SARS-CoV-2 to partially evade the defenses acquired by people naturally, after an infection . In fact, British scientists last week were very concerned about the possibility that the South African variant had the ability to partially evade the immune response triggered by vaccines.

Photomicrograph of various SARS-CoV-2 particles (in orange)
Photomicrograph of various SARS-CoV-2 particles (in orange) – NIAID

Tulio Oliveira, Director of the South African Research Innovation & Sequencing Platform (KRISP), has commented that work is being done against the clock to check the antibody response, from serum of naturally immunized people and with the vaccine, against the 501Y.V2 variant , and that your results will be ready in the next few days.

Phil Dormitzer, co-author of the study presented today and one of Pfizer’s experts on vaccines for viruses, has commented that more data on the effect of the other mutations of the British and South African variants will be published in the coming weeks. In addition, he recalled that Pfizer has already verified that 15 other mutations do not have a notable effect on the effectiveness of the antibodies generated by the vaccine.

Trust in vaccines

In addition to these trials with the Pfizer vaccine, the companies AstraZeneca, Moderna and CureVac are also looking at the protection that the antibodies generated by their vaccines confer against the variants. They have advanced that they hope they will be effective, but it is still unknown when they will publish the results of their investigations.

Many scientists have already commented that the current variants are not expected to cause very dramatic changes in how vaccines work. In the first place, because they produce an excess of antibodies and, secondly, because they generate a great variety of them: this allows them to recognize very different points of the protein S and that there are many options for one to work, even if the virus changes.

Finally, these vaccines also activate cellular immunity, which adds its strength to antibodies. Therefore, more mutations are expected so that the variants can markedly decrease the effectiveness of current vaccines.

“From what we know so far – Alfredo Corell, Professor of Immunology at the University of Valladolid, said last week – it does not seem that anything needs to be changed in the vaccination strategy. Only if there were more mutations and new strains appeared (variants with a different behavior), in which the structure of the S protein changes enough, it would be necessary to go to a model of mixing vaccines for different strains, as is done with the influenza virus or the pneumococcus » .

In any case, the companies Pfizer / BioNTech and Moderna, which have based their vaccines on messenger RNA technology, have already commented on several occasions that sYour vaccinations can be modified within six weeks to adapt them to a new variant.

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