The specialized proresolving mediator 17-HDHA enhances the antibody-mediated immune response against influenza virus: a new class of adjuvant?
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.
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; and.
Sesquile
S
Ramon
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642;
Steven F
SF
Baker
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642;
Julie M
JM
Sahler
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642;
Nina
N
Kim
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642;
Eric A
EA
Feldsott
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; and.
Charles N
CN
Serhan
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642;
Luis
L
Martínez-Sobrido
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642;
David J
DJ
Topham
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; richard_phipps@urmc.rochester.edu.
Richard P
RP
Phipps
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D056724:Immunity, Humoral / Q000187:drug effects*; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D008297:Male; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D010950:Plasma Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D004281:Docosahexaenoic Acids; C062894:17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid