We answer questions about COVID-19 vaccination in patients with allergies

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00:00, 07/15/2021 6 Story: All about coronavirus / COVID-19

Is the coronavirus vaccine safe if you have allergies?

Photo: mos.ru

How to get vaccinated against coronavirus and not end up in a hospital bed if you have a history of allergies? Guzel Zakirova, head of the city center of allergy and immunology of the State Clinical Hospital No. 7 of Kazan, told Tatarstan residents about the features of vaccination live on the account of the Republic’s Operational Headquarters to combat the spread of COVID-19. The immunologist also explained why taking antihistamines to protect yourself from a reaction to the vaccine is a bad idea. Realnoe Vremya has collected the doctor’s main recommendations for allergy sufferers.

How does an allergy occur?

An allergen is an antigen that causes an allergic reaction. An antigen (short for antibody-generating) is any molecule that, when introduced into the body, induces the production of antibodies. Most often, antigens are protein in nature.

When entering the body, the allergen molecule is fragmented by antigen-presenting cells (APCs) into short peptide chains (epitopes). After this, the epitopes are exposed on the surface of the APC in complex with molecules of the major histocompatibility complex (MHC, Major Histocompatibility Complex). In this form, they are easily recognized by T-lymphocytes, namely class 2 T-helper cells (Th2), which are then activated and begin to produce various cytokines and stimulate the production of IgE-type antibodies by B-lymphocytes [2].

The resulting IgE antibodies bind to FceRI, high-affinity receptors for the Fc fragment of IgE antibodies located on the surface of mast cells of mucous and connective tissues. As a result, these cells with “weapons” in the form of IgE antibodies are ready to react to the allergen if it re-enters the internal environment of the body (Fig. 1).

Figure 1. A mast cell with IgE antibodies on the surface and histamine-filled granules inside.

[3]

When the allergen binds to the IgE antibody, mast cells degranulate (break) and begin to secrete mediators: histamine, prostaglandin D2, etc., which, when bound to tissue receptors, trigger the development of rapid and delayed phases of the allergic reaction. More details about the mechanisms of the described processes can be found in [3]. I also recommend Royt's excellent immunology textbook [4].

And you will be cured, and you will also be cured, and I will be cured...

The radical and most effective approach to treating allergies in our time is allergen-specific immunotherapy (ASIT). It allows you to influence the manifestations of allergies caused by the formation of antiallergic antibodies - immunoglobulins E (IgE).

ASIT consists of sequentially introducing into the patient’s body increasing doses of an allergen to which the patient has been shown to be hypersensitive. It is this that causes the clinical manifestations of the disease.

According to the principle of action, the therapy is partially similar to vaccination against infectious diseases, forming acquired immunity in a person “vaccinated” with an allergen - a quick, effective and adequate reaction of the immune system upon contact with the allergen. Like vaccination, ASIT must be completed in advance (before the “meeting” with the allergen) or during the period of isolation from it. (For general information about infectious vaccines, see the article “Vaccines in Questions and Answers” ​​[5].)

Video. Interview with allergist L.N. Tislenko, who talks about ASIT in an accessible and entertaining way.

Below is an excerpt from the annotation for one of the traditional drugs for ASIT:

The exact mechanism of action of the allergen during allergen-specific immunotherapy (ASIT) is not completely clear. The following biological changes have been proven: the appearance of specific antibodies (IgG4), which play the role of “blocking antibodies”; decrease in the level of specific IgE in plasma for a long period; decreased reactivity of cells involved in an allergic reaction; increased activity of interaction between T-lymphocytes Th2 and Th1 and even Th0, leading to a positive change in the production of cytokines (decrease in IL-4 and increase in γ-interferon) that regulate the production of IgE. In addition, ASIT causes an immune response, which allows maintaining immunobiological memory for a long period.

ASIT is competent, first of all, in a variety of respiratory allergies, where the allergens are dust, house dust mites, plant pollen, and pet dander.

ASIT can significantly alleviate or completely cure allergy manifestations such as rhinitis, conjunctivitis, and prevents the development of bronchial asthma. The main advantage of therapy is its focus on changing the reactivity of the body’s immune system. As a rule, the effect of undergoing ASIT lasts throughout life.

TO THE POINT

A mask: when it can help an allergy sufferer and when there is a risk of an attack

Our country now has an anti-epidemic rule on the mandatory wearing of masks in public indoor spaces. During the dusting season, people with allergies are often advised to wear a protective bandage outside.

“Of course, this will help reduce the number of allergens that reach the mucous membranes through a mechanical barrier route,” confirms Valery Smirnov, head of the laboratory of the Institute of Immunology of the FMBA. “However, if a person does not follow the rule of regularly replacing the mask and remains in the same one on the street throughout the day, then the protective bandage will accumulate all kinds of pollen and allergens. And it will become a source of increased danger - the patient will interact even more with his allergen.

During the active dusting season, people with allergies are advised to change their masks at least every one and a half to two hours while outdoors.

You are wrong to call him adorable! *

* — quote from the movie “Heart of a Dog.”

The main disadvantage of ASIT is currently related to the origin of the drugs used. All of them are extracts from natural allergens. Despite the overall positive outcome of therapy, the side effects of such drugs remain significant. This is due to the fact that the target of the “whole” allergen, not processed by APC, is the immunoglobulin “antennas” of mast cells, and the entire cascade of allergic reactions starts anew, provoking an immune response similar in nature to the disease itself, but in a lighter form, which corresponds to the dose of the administered allergen .

In addition, there are some doubts regarding the quality and origin of allergy vaccines offered by medical institutions. It is not surprising, because even for the allergens underlying “manufactured” drugs, there are no generally accepted standards and criteria that determine the effect of the drug. The measure of effectiveness is the titer of IgE antibodies produced by the body. It turns out that the parameters of the immune system of a given organism are measured, and not the active substance (see pharmacokinetics, pharmacodynamics). Of course, there are statistics, but still such drugs remain empirically effective.

Also significant imperfections of ASIT are its duration and inconvenience - as a rule, treatment is a course of injections with different frequencies (from three times a week to once a month) or a tablet daily, and all this for three to five years.

It is impossible not to mention the high cost of therapy, which makes its implementation impossible for many people.

The simplest rules to easily transfer vaccination

Any vaccine is stressful for the body, the doctor recalled.

In this regard, Guzel Zakirova gave simple recommendations, following which you can minimize the possible unpleasant consequences of vaccination:

— The person should be well-fed, drink enough liquid, especially in the heat, before vaccination you should not be in the sun for a long time, the room should not be stuffy or hot. After vaccination, you need to stay in a medical facility for half an hour and not expose yourself to physical exertion or sun exposure.

An incredible success story

Not more than six months ago, Circassia, a company created at the University of Oxford, presented stunning results from the second phase of clinical trials of a synthetic polypeptide vaccine for cat allergies. (The model, methods and results of the clinical study can be found in detail in the original article [6].) The ability of the developed Tolero Mune vaccine to eliminate the factors that shape the disease as a whole is three times higher than that of all currently known drugs, including antihistamines and steroid drugs . The first significant results were observed in a year-long study of the effect of just four injections administered over 12 weeks (one injection every three weeks) [1].

The vaccine received even more attention when the results of a two-year study became known - a 50% relief of nasal and ocular allergy symptoms on the total index of rhinoconjunctival symptoms (TRSS) (the result of placebo was only 14.9%).

Even in the “extreme” four-day study, Tolero Mune did not disappoint: the improvement was 38.3% (13.4% for placebo). According to Steve Harris, head of Circassia, these are unprecedented results not only for allergology, but also for immunology in general.

Should people with autoimmune diseases be vaccinated or not?

In the case of a severe uncompensated disease, when the patient is under the supervision of rheumatologists, endocrinologists, neurologists, and other doctors, and is taking medications, there is a risk of developing an exacerbation of the underlying disease due to vaccination, the doctor believes.

— We need to approach vaccination carefully in this case, maybe make a medical withdrawal. But if an autoimmune disease - the same autoimmune therioditis, which is very common - is in the stage of compensation and correction, then there are no contraindications against vaccination.

Guzel Zakirova believes that it is safest for allergy sufferers to get vaccinated with Sputnik V (Gam-COVID-Vac), since, according to the doctor, there are no peptides, no protein inclusions, and the vaccine is low-component. Photo: mos.ru

Is the nature of the vaccine an obvious failure or a brilliant idea?

Synthetic vaccines are produced chemically in vitro. Despite the complete copying of the amino acid sequence of the allergen protein, they are characterized by low efficiency and require the addition of an additional immunogenic component - an adjuvant. It is not surprising - after all, how closely the antigen and antibody become friends largely depends on the spatial structure of the protein, and not just on the chemical composition. Synthetic proteins are linear, which ruins their chances of becoming a good vaccine.

The ToleroMune vaccine does not even contain an adjuvant. The idea seems to be a complete failure from the very beginning, but how did the vaccine creators achieve such significant results?

The idea of ​​using allergen epitopes as a vaccine was risky, but brilliant. They are very small linear peptides and are bound by immature antigen-presenting cells. Due to the presence of a constant “allergenic” background, T-helper 2 cells do not respond to every allergic attack with abundant production of IgE antibodies, and the cascade of reactions involving mast cells (as well as their biosynthesis) gradually loses its former intensity, and allergy symptoms do not develop. It is not the “interception” of already synthesized IgE antibodies that occurs, but the cessation of their synthesis in principle. Bravo!

Briefly, the technology for creating the Tolero Mune cat allergy vaccine looked like this:

1. Initially, those epitopes of the cat allergen (Fel d1) were identified that bound to molecules of the major histocompatibility complex II (the ten most common HLA-DR receptors) on the surface of APC and caused a reaction of T-lymphocytes [6] (Fig. 2).
2. After this, the epitopes were obtained in vitro by solid-phase peptide synthesis using the F-moc protective reaction and an in vivo test was performed to select those epitopes that attract T-helper 2 (Th2) cells responsible for the production of IgE antibodies. In addition, the histamine release factor was assessed for each of the epitopes (Fig. 3).
3. From the “elite” they formed a vaccine - a set of seven peptides, each of which contains one or two Th2-activating epitopes.

Figure 2. Complete epitope map of the Fel d1 allergen. The regions of binding to MHC II are highlighted by shading.

[6]

It turns out that the vaccine from Oxford scientists immediately eliminated the main disadvantages of ASIT:

1. The absence of an adverse reaction similar to the disease itself, as is the case with the use of a whole allergen.
2. Significant reduction in treatment time and easier administration - just four injections over 12 weeks. Alternative treatment regimens and dosage forms are also currently being developed.
3. The synthetic route for obtaining the vaccine makes it possible to reduce its cost and make it available to a larger number of patients.

Figure 3. Plot of histamine release as a function of the nature of the epitope. It shows that for all synthesized epitopes the factor is significantly lower than that of the whole cat allergen extract.

[6]

All of the above is a huge help to people who suffer from allergies constantly: during the flowering of trees and grasses, every time they encounter a cat or dust...

Literature

1. Randy Osborne. (2013). Synthetic peptide allergy vaccine shows efficacy. Nat Biotechnol
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   31 , 371-372;
2. Ilyina N.I. and Kurbacheva O.M. (2004). Vaccine prevention of allergies. Vaccinal prevention of non-communicable diseases. 4;
3. “Type I hypersensitivity reactions—mast cells and basophils.” Immunonfo.ru;
4. Royt A., Brostoff J., Meil ​​D. Immunology. M.: Mir, 2000. - 592 pp.;
5. Vaccines in questions and answers;
6. Margitta Worm, Hae-Hyuk Lee, Jörg Kleine-Tebbe, Roderick P. Hafner, Paul Laidler, et. al.. (2011). Development and preliminary clinical evaluation of a peptide immunotherapy vaccine for cat allergy. Journal of Allergy and Clinical Immunology
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   127 , 89-97.e14.