We are vaccinated from the variant of coronavirus, which we have not been sick for more than two years

When will vaccines finally update?

After a few months in countries where American drugs are available, updated anti -icing produced Pfizer and Moderna production vaccines should appear. Their new versions are directed against those variants of coronavirus that dominate the world right now, that is, against Omicron and its varieties. Until now, all the vaccines used in the world have been made against the original, Ulyan version of SARS-COV-2, which was once allocated in China and has long disappeared from circulation. At the same time, the significant differences between the old and diverse new coronavirus options (especially Omicron) were the main reason for reducing the effectiveness of vaccines in the last year of the pandemic. About why the renewal of drugs had to wait as long as the additional protection that new vaccines can be given on the eve of the possible increase in incidence, and whether it was worth waiting for the Russian “satellite”, “Medusa” asked to tell Ilya Yasny, the head of the scientific examination inbio Ventures .

Clinical studies of the effectiveness of updated vaccines took place on the initiative of manufacturers over the past last months, and a discussion of the need for such a step is even longer. The very decision to update the vaccines stretched for three days:

• On June 28, the Independent Committee on vaccines and biological products (VRBPAC), in American control over food control and medicine control (FDA), issued a recommendation to include components that protect against Omicron's options (a previous decision was made by the WHO Commission).
• On June 29, the US Department of Health, together with the Department of Defense, announced the allocation of $ 3.2 billion for new vaccines.
• On June 30, the commission’s decision was approved by FDA: to develop a modified option against Omicron Ba.4/5 strains and add it to the original vaccine version in order to get a bivalent booster vaccine for the beginning and in the autumn of 2022. For vaccinating, the agency for the first time recommends using the initial version of the vaccine.

Now more. During a whole day of reports and discussions within the framework of the VRBPAC commission (materials and entry can be viewed here , at the same time assessing the degree of publicity and transparency of the decision -making procedure in the United States), the following issues were discussed:

1. Is it necessary to recommend a booster vaccination in anticipation of a possible new wave in the fall?
2. If so, whether vaccination should be carried out by the initial vaccines (the prototype of which appeared at the beginning of 2020) or their changed options?
3. If changed, then should the vaccines be directed to the Omicron Ba.½ or Ba.4/5 option?
4. Do I need to combine the changed option with the original or is it better to use only the changed option?

These are difficult questions, and they require quick solutions in conditions of incomplete information: epidemiological modeling shows that in the fall of the United States can cover with a new wave of coronavirus and, depending on the script and if the country continues to use existing vaccines, this can result in 90–210 thousand deaths per year. Meanwhile, modified vaccines against the Omicron BA.1 option have been tested for several months in public, and so far there is data only on the production of neutralizing antibodies, but there is no data on protection against infection, hospitalization or death.

During the meeting of the Committee, clinical data on new vaccines against wa 1 were presented, and they showed good efficiency against VA. 1 (albeit decreasing over time), but noticeably smaller - against the new options BA.4 and VA.5, which are already up to 50% of the new cases of Covid in the United States. Manufacturers also presented the results of animal testing new vaccines, directed precisely against VA.4 and VA.5. Such drugs turned out to be expected to be more effective in terms of generating neutralizing antibodies. However, it should be borne in mind that it is impossible to reliably establish on animals whether the growth of neutralizing efficiency is enough to increase protection in people and how long it turns out to be.

The concern of all experts is due to the fact that coronavirus, as it turned out , evolves faster than humanity makes (and puts into circulation) vaccines, and Omcron's options very well avoid an immune response formed by already outdated drugs.

What did you decide in the USA? What are the new vaccines?

To the first question, the answer is unambiguously positive: the centers for the control and prevention of diseases (CDC) of the United States showed data on booster vaccination, according to which the second booster (that is, the third vaccination ) reduces the likelihood of death in people over 50 years old compared to one booster (and 42 times compared to unuscinated).

Moreover, we are talking about an unmodified vaccine. All experts agree that even the original version of the vaccine continues to protect well from severe currents and death, but the protection against infection falls quite quickly and is ineffective against Omicron options.

Regarding the second question, a formal vote was held, and 19 votes against two spoke out in order to include a changed version of the vaccine (against Omicron) in the booster. Among the two specialists who opposed, Paul Offit turned out to be a very respected specialist and one of the developers of the measles vaccine. After voting, he substantiated his point of view in detail. If briefly, the offite believes that the data for preferred modified vaccines is not enough, the growth of neutralizing antibodies may not result in an increase in efficiency, and the decision to unfold new vaccines will cost tens of billions of dollars. He calls not to rush and continue to collect data, but in addition to think about the selective use of new vaccines - for example, only in the elderly.

On the third issue, there was no unanimity either. Opponents of the use of the newest vaccines say that the predicted new wave may not be caused by wa.4/5, but some new option against which the Vaccine Va.4/5 will have reduced efficiency (for example, in India, for example, the new version of Ba.2.75 is actively spreading; it has eight mutations on the area 5 in the area against which the antibodies are directed, which, perhaps, gives him the ability to infect him ill and vaccinated even more efficiently than Va.5). In addition, the vaccine will be needed this fall, and judging by the speed of the vaccine against BA.1, large -scale production against new options is developed before six months later.

Regarding the fourth question, a conflict arose in general - Pfizer/Biontech and Moderna resulted in the studies that at first glance contradict each other: Pfizer/Biontech, a monovalent vaccine, turned out to be more effective than a bivalent, but, on the other hand, in Moderna, a bivalent had a longer effect. It was impossible to compare vaccines directly by these parameters, so this last question will require further study.

What is the legal status of this solution: is this a recommendation or requirement? How did the vaccines manufacturers react to it?

Formal voting was carried out only on the issue of inclusion of the Omicron component in booster vaccines against Covid-19 in the United States. The commission voted in 19 votes against two for this recommendation. The FDAs expressed during the discussions were taken into account, and the agency eventually decided to create bivalent vaccines with the component against BA.4/5 - this indication becomes mandatory for manufacturers. It is impossible to leave such an important issue to manufacturers, because state money will be spent on the purchase of vaccines and, if there are different vaccines options, their usefulness will turn into a nightmare.

At the same meeting, manufacturers asked the FDA to allow new vaccines to release new options at all without clinical research, as is done in the case of flu vaccines - then the release will happen much faster. More cautious experts say that the correlation of non -linear data with effectiveness for coronavirus vaccines has not yet been sufficiently studied to go to such a step. FDA writes that now they will not register bivalent vaccines against BA.4/5, but they want to first wait for complete clinical data on vaccines against BA.1. These data may be enough to register a vaccine against BA.4/5, but manufacturers will still have to start clinical studies of these new bivalent vaccines.

When can a new version of vaccines appear?

Representatives of Pfizer announced that the new version of the vaccine will be ready by the beginning of October. True, the company did not comment on in which quantities it will be produced by this moment. Moderna said that by the end of October I was ready to put an updated option on a significant scale. The representative of NOVAVAX said that in the fourth quarter the company will be able to make an updated option - however, even the original version of this vaccine is still not registered in the United States.

And what about Russian vaccines?

In Russia, only two proven vaccines: “Satellite V” and “Light satellite” (representing the first component of “satellite V”).

The latest publication about the “satellites” was released on June 13, 2022 in the Vaccines journal, it studied the effectiveness of vaccination for January - February 2022, when the Omicron Ba.½ option dominated in Moscow. As for other vaccines, the authors noted the fall of the level of neutralizing antibodies over time, but it is difficult to say how much it affects the protective ability of the vaccine - there is no data yet. As in the case of other vaccines, the Boster dose of the “satellite” increases the level of neutralizing antibodies and provides protection against hospitalization with an efficiency of 97% - for those who received more than three injections (that is, they have passed complete vaccination and made one or two boosters).

According to TASS, in Russia the first genomes of variants of VA.4/VA. 5 were detected in late May. At the end of June, the share of the VA.5 variant among decrypted genomes of patients from Russia was about 6%, but it grows rapidly. There is no data on the activity of "satellites" against VA.4/5 yet.

What are the difficulties with the vaccine update, why was it made only now?

Probably, they were in no hurry with the update, because some of the specialists believe that since the booster still protects the original option from hospitalization and death, it is not necessary to change anything - after all, these are extra risks and costs. In their opinion, it is necessary to focus on more universal ( pankoronaviral ) vaccines and nasal form, which will be better protected from infection. The latter is sprayed through the nose and should activate the immunity of the mucous membranes (mucosal) against coronavirus. Thus, the coronavirus will not be neutralized when it has already reached the circulatory system and lungs, but “on the approach”, in the upper respiratory tract. Such vaccines are now undergoing clinical studies, there are no results of their effectiveness yet. In Russia, the nasal version of the "satellite" is already registered , but now it is not available due to the lack of nozzles for spraying).

The discussion about the addition of new vaccines to the booster became possible in essence only when manufacturers have data on the immunological efficiency of vaccines against BA.1. In addition, now more data has accumulated about the dynamics of the development of the COVID-19, the results of modeling have appeared, which indicate a high probability of a new wave in the fall. Against this background, the decision to update anti -icing vaccines no longer seems so belated.

Ilya is clear