A team of Russian scientists carried out a study on the cell immunity level and found out how an adjuvant called azoximer bromide increases the immunogenicity of the anti-flu vaccine. The results of the study were presented at the Russian-Chinese Symposium on Infectious Diseases in Saint-Petersburg (5-7 November, 2019).

The risk of epidemics increases with the growth of our planet's population and migration levels. To avoid it, scientists all over the world work on creating new vaccines that have to be more efficient and available to the wide audience. One of the ways to do it is to add adjuvants - substances that increase the immune response to the injected antigen, i.e. an 'enemy' molecule for the immune system to fight with antibodies. If a vaccine is produced with an adjuvant, less active substances are required for its manufacture. This effect was discovered by the bacteriologists Alexandre Yersin (the one the plague bacillus, Yersinia pestis, is named after) and Emile Roux. They noticed that the immune response in animals vaccinated with diphterin increased if calcium chloride was added to the vaccine. 

"The use of adjuvants allows to apply so-called antigen-sparing strategy. If more vaccine can be produced from the same amount of antigens, the manufacture can be launched faster, and more people can be vaccinated within shorter periods of time, which is extremely important during epidemics. Moreover, the antigens are foreign proteins for our bodies, and the less of them is injected, the lower is the risk of side effects," commented Alexey Matveichev, the head of Petrovax Center for Preclinical Studies.

Azoximer bromide has been used in Russian anti-flu vaccines by Petrovax for over 20 years. The adjuvant allows for triple reduction of the antigen dosage compared to the vaccines without any additional substances. Several clinical studies were carried out to confirm the efficiency of this dosage and the safety of the vaccine (please see the review of the studies here: https://www.epidemvac.ru/jour/article/view/794). However, the requirements for the evidential base of vaccines keep getting stricter, and the studies need to go on. The company continues to carry out the research of the adjuvant's action mechanism. The new data obtained in the course of this research was presented at the symposium.

"These results were acquired nearly a year ago. In line with international practices, the majority of the experiments were carried out on mice. We studied the effect of azoximer bromide on human dendritic cells (one of the key initiators of the immune response to vaccination) and mice nk-cells. We also found new evidence explaining how this adjuvant helps the development of humoral immune response (antibody response) which is the main goal of vaccination. Moreover, we studied cell-mediated immune response which is extremely important if a person gets infected and the virus starts to reproduce itself in the cells. In this case cell-mediated immune response helps identify and destroy the infected cells", commented Alexey Matveichev.

The animals were divided into four groups, and each group was injected with one of the studied components: vaccine antigens with and without the adjuvant, a vaccine with a standard amount of the antigen, or a vaccine solution used as placebo. After that the researchers analyzed the ability of the animal cells to participate in humoral and cell-mediated immune response, i.e. to divide, synthesize cytokines (important soluble proteins), and kill target cells similar to infected ones. All these actions are parts of the complex process that is immune response, and they determine its efficiency. The work showed that in the presence of the adjuvant (azoximer bromide) the vaccine that contained a lesser amount of antigens worked as efficiently as the one with three times higher antigen content. Vaccination also increases the activity of natural killers: they start to fight infected cells more efficiently, supposedly helping a sick person to recover from flu (or a cold) faster.

"In this study we worked with the so-called immune response effectors, i.e. with the cells that directly fight the infection. But before 'soldier cells' attack, they need to get their orders, otherwise they simply won't notice the enemy. Therefore, the next stage of our study covered the effect of the adjuvant on 'immune response generals', that is, dendritic cells", added Alexey Matveichev.

In this experiment the team used human dendritic cells provided by healthy volunteers. A vaccine with the adjuvant turned out to increase the speed of their maturing and migration. As soon as such a cell reaches a lymph node, the immune response starts to develop, and body defences begin to form. Speed is of the issue here, especially on the later stages of a pre-epidemic period, or at increased risks of a pandemic.

According to the expert, azoximer bromide-based vaccines have been used in Russia and numerous other states since 1996. Moreover, the potential use of this adjuvant is not limited to anti-flu vaccines. Previous research has shown its ability to activate the immune response to a wide range of other socially significant pathogens affecting both humans and animals. Azoximer bromide demonstrates the potential of a universal vaccine adjuvant and meets world efficiency and safety standards.