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Scientists have explained how an additional component can triple the effect of a vaccine

With an increase in population and an increase in the level of migration of the world’s population, the risk of major epidemics also increases. To prevent them, scientists around the world are working on ways to create highly effective vaccines that will simultaneously be more accessible for immunization. One way to achieve this is by adding an adjuvant to the vaccine. This is the name of a substance that enhances the immune response to an introduced antigen, that is, an “enemy” molecule against which the immune system will produce antibodies. Using this component, you can reduce the amount of the main active substance of the vaccine. Bacteriologists Alexander Yersen (the plague stick was named after him) and Emil Roux discovered this effect at the end of the 19th century. Scientists have noticed that the immune response after vaccination of animals with diphtheria toxin was enhanced when calcium chloride was added to the vaccine.

“The use of adjuvants allows the vaccine manufacturer to implement the so-called“ antigen-saving ”strategy. If we can produce more vaccines from the same amount of antigens, we can quickly deploy production and vaccinate more people in a short time, which is especially important in an epidemic. In addition, if we introduce fewer antigens into the body that are proteins foreign to the body, we will reduce the likelihood of side effects, ”said Alexey Matveichev, head of the Petrovax Center for Preclinical Studies.

For more than 20 years, azoximera bromide has been used in Russian influenza vaccines manufactured by Petrovax. Thanks to the adjuvant, these vaccines contain a 3 times lower dose of virus antigens compared to the adjuvanted vaccines. To substantiate the effectiveness of such a dosage and the safety of drugs, several clinical trials have been conducted (you can read about them in the review). However, modern requirements for the evidence base of vaccines are being tightened, and research does not end there. Further research is ongoing to study the mechanism of action of the adjuvant. New data were presented at the symposium.

“These are the results that were obtained about a year ago,” explained Alexei Matveichev. – In accordance with international practice, the main experiments were carried out on mice. We studied the effect of azoximer bromide on human dendritic cells (one of the key cells that trigger the immune response to vaccination) and natural killer cells in mice. We also found new confirmation of how this adjuvant promotes the development of a humoral immune response (antibody production), and the launch of a humoral immune response is the main goal of vaccination. We also examined the cellular immune response, which is especially important for our defense, if infection did occur and the virus began to multiply in the body’s cells. “A cellular immune response aimed at combating cells infected with the virus will ensure their recognition and destruction.”

The mice in the experiment were divided into four groups, and each group was administered one of the test components: vaccine antigens without adjuvant, vaccine antigens with adjuvant, vaccine with a standard dose of antigen or vaccine solvent, which was used as a placebo. After that, the researchers evaluated the ability of cells of vaccinated mice to participate in the humoral and cellular immune response: the ability to divide, synthesize important soluble proteins – cytokines, the ability to kill target cells similar to cells infected with the virus. All these features are integral parts of the complex process of the immune response, indicating its effectiveness. In the course of the work, it was shown that thanks to the adjuvant of azoximer bromide, a vaccine containing less antigens works just as effectively as one in which there are 3 times more antigens. Thanks to vaccination, the activity of natural killers also increases: they begin to fight more intensively with cells infected with the virus. Thus, if a person is still ill not only with the flu, but also with other acute respiratory viral infections, recovery can come faster.

“In this study, we worked with the so-called immune response effectors, that is, with cells that directly enter the fight against infection. But someone must give the order to start the fight, otherwise the effector cells simply will not see the “enemy”. Thus, our next step was to study the effect of the adjuvant on “generals of the immune response” – dendritic cells, ”added Alexey Matveichev.

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