Abstract
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 Ulva lactuca, brown algae Sargassum pallidum, and seagrass Zostera marina. 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 S. pallidum, which provided the relaxation of the spatial structure and, likely, the proper presentation of the antigen to immunocompetent cells.
Highlights
Viruses of Influenzavirus A genus, which belongs to the Orthomyxoviridae family, are the cause of all flu pandemics
MGDGs isolated from green a3logfa1e1 U. lactuca, brown algae S. pallidum, and seagrass Z. marina differ in their fatty acid composition [13] aUn.dla, ctthuecrae,fborroe,wmnicarlogvaiescSo. spiatylli[d1u0m].,AasndshsoewagnrianssFZig.umrear1i,nHa dAi1ffaelroinnethweaisr ifmatmtyuancoidgecnoimc.pItoisnitdiounce[d13a] 1a.n7d-f,otlhderheifgohreer, mlevicerloovfisacnotsii-tHy A[110]a. nAtisbsohdoiewsncoinmFpiagruerde 1w, iHthAt1healcoonnetrwoal.sIinmtmurunn,oagllenoifct.hIet isntduudcieedd TaI1-c.7o-mfopldlehxeigshsetrimleuvlealteodf aant1i-.3H–A1.18 atnimtibeos dhieigshceormimpamreudnwe irtehspthoencsoenttoroHl
Modern genetic engineering allows obtaining HA proteins in bacterial expression systems and more rapidly producing subunit recombinant influenza vaccines, compared to traditional egg-based vaccine production techniques [18], which is especially important in a pandemic
Summary
Viruses of Influenzavirus A genus, which belongs to the Orthomyxoviridae family, are the cause of all flu pandemics. The causative agent of the first and the most aggressive flu pandemic of the 20th century, the Spanish flu, which killed 20–40 million people worldwide in 1918–1919, was the Influenza virus A subtype H1N1. This subtype circulated in different variations among the global population until 1957. In 1977, H1N1, this time with very similar antigenic properties, appeared again, and has been recurring in the human population ever since. In 2009, a new influenza virus, which was a subtype of H1N1 but differed antigenically from previously circulating viruses, spread rapidly around the world [1]. Molecular genetic studies have shown that the A (H1N1) pdm2009 Influenza Strain is a triple reassortant, carrying avian, human, and swine influenza virus A gene segments [2]
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