Development of B-cell response during immunization with inactivated influenza vaccines "Grippol plus", "Sovigripp" and "Ultrix"

Abstract

The worldwide circulating influenza viruses annually lead to serious medical and socio-economic consequences. It is generally recognized that vaccination is the most effective and safe strategy for preventing influenza and its complications. In order to reduce side effects when using live viruses, split and subunit influenza vaccines are widely used. To date, the characteristics of B cell response after immunization with influenza vaccines remain insufficiently studied. The aim of our study was to compare the effects of immunization with different influenza vaccines, i.e., “Sovigripp”, “Grippol plus” and “Ultrix”, on the B cell response. The study was conducted on the base of Clinical Department at the A.Smorodintsev Influenza Research Institute during the epidemic flu season of 2018-2019. For clinical studies, venous blood samples were obtained from 39 volunteers before vaccination, on the 7th and 21st days after vaccination. The subpopulations of B cells were analyzed by flow cytometry using fluorescently labeled antibodies to CD3, CD19, CD20, CD27, CD38, IgD, IgA surface antigens (BioLegend, USA). Cryopreserved mononuclear cells (1 × 106 cells/sample) were used for analysis. The processing of flow cytometry data was carried out with special software (H., Cytexpert, Beckman Coulter, Inc., USA) and Kaluza 2.0 (Beckman Coulter, Inc., USA). The differences with pre-vaccination data were evaluated using the Mann–Whitney U-test and being considered significant at p < 0.05. As a result of the studies, the following subpopulations of B lymphocytes (CD3-CD19+) were specified: naive B cells (CD20+CD27-IgD+), non-switched memory B cells (CD20+CD27+IgD+), switched memory B cells (CD20+CD27+IgD-), effector memory B cells (CD20+CD27-IgD-), plasmablasts (CD20-CD38hiCD27hi). Activation of the B cell immune response was assessed by measuring the relative content of CD38+B cells belonging to subpopulations of naive, effector B lymphocytes, switched and non-switched memory B cells. The analysis of B cell response showed an increase in both the total number of B lymphocytes and their subpopulations including plasmablasts and activated switched memory B cells after immunization. With adjuvant vaccines “Grippol plus” and “Sovigripp”, as compared with the split “Ultrix” vaccine, an early increase in relative counts of plasmablasts was shown on the 7th day of the study. At the same time, all three vaccines equally contributed to an increase in the number of activated memory B cells with a switched antibody isotype. Thus, the assessment of B cell response revealed significant changes in contents of peripheral blood B cell subpopulations in response to vaccination with “Grippol plus”, “Sovigripp”, or “Ultrix”.

Keywords

• influenza vaccines
• b-lymphocytes
• flow cytometry
• plasmablasts
• memory b cells
• influenza virus