Modulation of Immunogenicity and Conformation of HA1 Subunit of Influenza A Virus H1/N1 Hemagglutinin in Tubular Immunostimulating Complexes

• Published in: International journal of molecular sciences 2017-09, Vol.18 (9), p.1895
• Main Authors: Sanina, Nina, Davydova, Ludmila, Chopenko, Natalia, Kostetsky, Eduard, Shnyrov, Valery
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - chemistry; Algae; Animals; Antibodies, Viral - immunology; Antigen presentation; Antigens; Antigens, Viral - chemistry; Antigens, Viral - immunology; Biocompatibility; Calorimetry, Differential Scanning; Conformation; Cytokines; Cytokines - metabolism; Differential scanning calorimetry; Enzyme-linked immunosorbent assay; Fluorescence; Galactolipids - chemistry; Galactolipids - pharmacology; Heat measurement; Hemagglutinin Glycoproteins, Influenza Virus - chemistry; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinins; Hydroxyapatite; Immunization; Immunogenicity; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype - immunology; Influenza Vaccines - immunology; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Macrophytes; Male; Mice; Protective coatings; Protein Conformation - drug effects; Protein Denaturation; Surgical implants; Vaccines
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18091895

The HA1 subunit of the influenza virus hemagglutinin (HA) is a valuable antigen for the development of vaccines against flu due to the availability of most antigenic sites which are conformational. Therefore, a novel adjuvanted antigen delivery system, tubular immunostimulating complexes (TI-complexes) comprising monogalactosyldiacylglycerol (MGDG) from different marine macrophytes as a lipid matrix for an antigen, was applied to enhance the immunogenicity of recombinant HA1 of influenza A H1N1 and to study the relation between its immunogenicity and conformation. The content of anti-HA1 antibodies and cytokines was estimated by ELISA after the immunization of mice with HA1 alone, and HA1 was incorporated in TI-complexes based on different MGDGs isolated from green algae , brown algae , and seagrass . Conformational changes of HA1 were estimated by differential scanning calorimetry and intrinsic fluorescence. It was shown that the adjuvant activity of TI-complexes depends on the microviscosity of MGDGs, which differently influence the conformation of HA1. The highest production of anti-HA1 antibodies (compared with the control) was induced by HA1 incorporated in a TI-complex based on MGDG from , which provided the relaxation of the spatial structure and, likely, the proper presentation of the antigen to immunocompetent cells.