On the tip of the needle

All of the developed vaccines can be divided into several types according to the platforms on which they are developed. Each of them has its pros and cons, development time.

In speed through clinical trials in the global vaccine race is now leading ChAdOx1-S vector-based. It is a joint development of the University of Oxford and company AstraZeneca, which is already gaining volunteers for the third phase of clinical trials in the UK, USA and Brazil. Also nimble enough turned out to be vaccine-based nucleic acid — they make up almost half of the “debiasi” to drugs.

If you look at the geography of the vaccines in the clinic, then the number of expected leads China (7 of 17). Several clinical studies carried out at institutions and companies in the US and the UK, there are Korean, German andn developments.

Despite these rankings and the fact that some developers have already voiced the approximate time of the issue of vaccines, focusing on them is not necessary — too much can go wrong. To register a vaccine must pass three phases of clinical trials. Among the 70% that pass the first level on the second survival of about 30%, still a little caught on the third. As a result, until the market reaches a few.

With each new level increases and the time to overcome it — if the first stage can be completed in months, the second and third last for the year. The average time of vaccine development from scratch about ten years. Since 1967, the world record belongs to the mumps vaccine, it was made and endorsed for four years. Vaccine rVSV‐ZEBOV against Ebola virus, clinical trials of which began in 2014, was approved only at the end of 2019 — and it is the most rapid “sprint” in recent years, largely motivated by Ebola outbreaks in Africa.

While most vaccines do not even the results of preclinical studies, so to speak with certainty about which of them and when it’s ready — too early. However, few details are known about the design of vaccine candidates. Knowing the background to their creation and fate of vaccines of the same type, we can predict their strengths and weaknesses. Below we have collected all that is known at the moment about then vaccine, which — if they end up in industrial production and the need for vaccination will not disappear — we have to deal with.

Still on the list who has 10 candidates. 37 about the other vaccines mentioned in may, Deputy Prime Minister Golikova, but missing in the list who knows very little. We know about the development belonging to the Federal scientific center im. Chumakov, Institute of Bioorganic chemistry of RAS, Institute of experimental medicine and Kazan Federal University.

An ideal vaccine needs to possess several properties. First, it should be safe. In the case of SARS-Cov-2 is a particularly delicate moment: a major percentage of severe patients are people with weakened immune systems, which is easy to hurt. Second, it should cause a steady, but not excessive antiviral response. The third component of success is the accuracy of the immune response: he must find the pathogen in any situation and not to confuse it with anything else. Also important is the convenience and price of the vaccine: how much it costs to manufacture, how easy is it to establish how it is stored.

Part of the success lies in the proper selection of the area of the virus that must remember remember the immune system. In most of the developed synthetic coronavirus vaccines are different parts of the S-protein (which the virus attaches to human cells). What is the difference between these components of then vaccines is still unknown.

But in order for the immune system remember the antigens is not enough simply to “believe” in person. The immune system need to show these antigens in the right place and at the same time to “explain” that this is something dangerous, and hint how to respond at the meeting — because there are different patterns of immune response to viruses, bacteria or intestinal parasites. This can be realized using different approaches, each of which has its advantages and disadvantages.

Break virus

(10 vaccines in the list of the who, 1 in our country)

There are several ways to simulate the attack of this pathogen. The
easiest to feed the immune system real
virus, hopelessly tainted with heating or chemical treatment.
Vaccines of this class — inactivated well — studied and
it has long been used in practice.

It is this drug doing to FNTS them. Chumakov (not on the list who). According to forecasts of Director General of the center, preclinical
tests will not be completed until August, and clinical in January.

The disadvantage of such vaccines is that the viruses broken attract attention
immunity is worse than active, and his memory is shorter. So you have
stimulate it with additional stimuli. In addition, for
development and production required a lot of work with pathogenic strains that
it is not always convenient and generally increases the security requirements.

On the other hand, work with any whole viruses are convenient because
the researcher there is no need to choose details-antigens, which
like the immune system — she gets everything and decide.

To weaken the virus

(2 in the list who 0 — in our country)

Another approach is to “taming” of the virus by a long
cultivation in cell cultures and animals dangerous strain accumulates mutations and
becomes unable to fully infect a person. So arranged classical measles vaccine.

Weakened
(an attenuated) viruses cause vivid and long-lasting immune response, but also not very easy to
designing: need to work with the pathogenic strains to develop each new
a vaccine from scratch, and then long to prove that “domesticated” strain safe. When
such vaccines can not recommend to use for elderly and disabled people
a weakened immune system, their body can not cope with weakened
virus.

In the list who have a couple of organizations that put on this type
vaccines against coronavirus, but in our country such developments do not go.

Fake virus

(36 in the list of the who 5 —)

The third approach is one of the most
used now to construct hybrid virus or vector. While “into battle” regulators allowed only one vaccine this class is a vaccine against Ebola virus, approved in 2019 the us FDA and the European Agency of medical products. Several of these are in the final stages of validation.

This method is good for its versatility, — only changing the filling, you can
relatively quickly to develop a different vaccine.

At the same time, you have to very carefully select the antigens for insertion into
packaging the virus and be confident that the immune system will be able to identify
and to reach them with this infection.

In terms of “coronavirus racing” the most convenient way to reduce the time
production is to work with such versatile pieces that
just need to insert any specific virus antigen. In addition
acceleration, the use of seeds reduces the cost of development and increases the chances
of the drug to reach the market: their security already verified, so the chance
to the harmful modification of the lower than brand new version. Ways to “fake” virus two.

First method: nonreplicating viral
vectors (19 in the list of the who, 1 in our country).

What it is. In nature, adenoviruses cause colds, but to make them safe
carriers, their “castrated” — clean up needed for the reproduction and genes
instead, insert the desired genes viral “stuffing”. But outside such
the design looks like a real adenovirus, she retained the ability
infect cells and cause them to synthesize their proteins. SOS signals from the infected
cells and viral proteins attract the attention of the immune system and provoke
response, and so together with the proteins of the virus shell immune cells
characterized and the proteins of the pathogen.

Who’s doing it. An example of this design can serve as a recombinant adenovirus 5 serotype, on the basis of which make the vaccine in NICAM them. Gamalei. This is the only vaccine that is nearing clinical trials in the country. It’s not their first adenoviral development: earlier there made a vaccine against Ebola was in our country and passing the last — fourth — phase clinical trials. In 2019, the center began clinical trials of similar vaccines against MERS and its modification formed the basis of a new vaccine against SARS-CoV-2.

Adenovirus vaccines prepared foreign teams, among them CanSino Biologics, Johnson & Johnson and Oxford University. At the heart of their work are studies of this type of vaccines for other diseases — Ebola virus, Zeke and human immunodeficiency.

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