The specialized proresolving mediator 17-HDHA enhances the antibody-mediated immune response against influenza virus: a new class of adjuvant?

J Immunol. 2014 Dec 15;193(12):6031-40. doi: 10.4049/jimmunol.1302795. Epub 2014 Nov 12.

Abstract

Influenza viruses remain a critical global health concern. More efficacious vaccines are needed to protect against influenza virus, yet few adjuvants are approved for routine use. Specialized proresolving mediators (SPMs) are powerful endogenous bioactive regulators of inflammation, with great clinical translational properties. In this study, we investigated the ability of the SPM 17-HDHA to enhance the adaptive immune response using an OVA immunization model and a preclinical influenza vaccination mouse model. Our findings revealed that mice immunized with OVA plus 17-HDHA or with H1N1-derived HA protein plus 17-HDHA increased Ag-specific Ab titers. 17-HDHA increased the number of Ab-secreting cells in vitro and the number of HA-specific Ab-secreting cells present in the bone marrow. Importantly, the 17-HDHA-mediated increased Ab production was more protective against live pH1N1 influenza infection in mice. To our knowledge, this is the first report on the biological effects of ω-3-derived SPMs on the humoral immune response. These findings illustrate a previously unknown biological link between proresolution signals and the adaptive immune system. Furthermore, this work has important implications for the understanding of B cell biology, as well as the development of new potential vaccine adjuvants.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibodies, Viral / immunology
  • Antibody Formation / drug effects
  • Antibody Formation / immunology
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / drug effects
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Docosahexaenoic Acids / pharmacology*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Immunity, Humoral / drug effects*
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Male
  • Mice
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / virology
  • Plasma Cells / cytology
  • Plasma Cells / drug effects
  • Plasma Cells / immunology
  • Plasma Cells / metabolism

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin G
  • Immunoglobulin M
  • Docosahexaenoic Acids
  • 17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid