title: On the possibility of lipid-induced regulation of conformation and immunogenicity of influenza a virus H1/N1 hemagglutinin as antigen of TI-complexes.
abstract: The tubular immunostimulating complex (TI-complex) consisting of cucumarioside A2-2, cholesterol and monogalactosyldiacylglycerol (MGDG) from marine macrophytes is the perspective antigen delivery system for subunit vaccines. MGDG is a lipid matrix for the protein antigen incorporated in the TI-complex. The aim of the present work was to study the influence of MGDGs from different macrophytes on conformation and immunogenicity of the secreted recombinant uncleaved hemagglutinin monomer (HA0S) of influenza A virus H1/N1. Differential scanning calorimetry, fluorescence spectroscopy and circular dichroism showed a dependence of the conformational changes of HA0S on the microviscosity of MGDG. The most viscous MGDG from Zostera marina induced the strongest rearrangements in protein conformation. Immunization of mice with HA0S within TI-complexes comprising different MGDGs resulted in an approximately 2-fold increase of the levels of anti-HA0S antibodies and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared with those induced by HA0S alone. TI-complexes based on MGDG from Z. marina stimulated the maximal production of GM-CSF. However, humoral immune response (anti-HA0S antibodies), unlike cell-mediated immune response (GM-CSF), did not depend on the physicochemical properties of MGDGs. It is assumed that this is due to the different localization and conformational lipid sensitivity of the HA0S regions, which are responsible for these types of immune responses.
authors: Department of Biochemistry, Microbiology and Biotechnology, Far Eastern Federal University, Vladivostok, Russia.
authors: Natalia
authors: N
authors: Vorobieva
authors: Nina
authors: N
authors: Sanina
authors: Vladimir
authors: V
authors: Vorontsov
authors: Eduard
authors: E
authors: Kostetsky
authors: Andrey
authors: A
authors: Mazeika
authors: Alexander
authors: A
authors: Tsybulsky
authors: Natalia
authors: N
authors: Kim
authors: Valery
authors: V
authors: Shnyrov
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D002151:Calorimetry; D002942:Circular Dichroism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology*; D008081:Liposomes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology; D035962:Zosteraceae / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D008081:Liposomes; D022223:Vaccines, Subunit; D016178:Granulocyte-Macrophage Colony-Stimulating Factor