Immunomodulation of TH2 biased immunity with mucosal administration of nanoemulsion adjuvant.
TH2-biased immune responses are associated with inadequate protection against some pathogens and with cancer, colitis, asthma and allergy. Since most currently used vaccine adjuvants induce a TH2-biased response, this has led to interest in developing adjuvants capable of activating TH1 immunity and modulating existing TH2 responses. Immunotherapies to shift immune responses from TH2 to TH1 have generally required prolonged immunization protocols and have not induced effective TH1 responses. We have demonstrated that nanoscale emulsions (NE), a novel mucosal adjuvant, induce robust IgA and IgG antibody responses and TH1/TH17 cellular immunity resulting in protection against a variety of respiratory and mucosal infections. Because intranasal (i.n.) delivery of NE adjuvant consistently induces TH1/TH17 biased responses, we hypothesized that NE could be used as a therapeutic vaccine to redirect existing TH2 polarized immunity towards a more balanced TH1/TH2 profile. To test this, a TH2 immune response was established by intramuscular immunization of mice with alum-adjuvanted hepatitis B surface antigen (HBs), followed by a single subsequent i.n. immunization with NE-HBs. These animals exhibited increased TH1 associated immune responses and IL-17, and decreased TH2 cytokines (IL-4 and IL-5) and IgG1. NE immunization induced regulatory T cells and IL-10, and IL-10 was required for the suppression of TH2 immunity. These data demonstrate that NE-based vaccines can modulate existing TH2 immune responses to promote TH1/TH17 immunity and suggest the potential therapeutic use of NE vaccines for diseases associated with TH2 immunity.
Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI 48109, United States.
Anna U
AU
Bielinska
Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI 48109, United States; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, MI 48109, United States. Electronic address: jjoz@umich.edu.
Jessica J
JJ
O'Konek
Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI 48109, United States.
Katarzyna W
KW
Janczak
Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI 48109, United States; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, MI 48109, United States. Electronic address: jbakerjr@umich.edu.
James R
JR
Baker
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D016207:Cytokines / Q000276:immunology; D004655:Emulsions / Q000008:administration & dosage; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D049329:Nanostructures / Q000008:administration & dosage*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004655:Emulsions; D006514:Hepatitis B Surface Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G
Adjuvant; Immunogenicity; Intranasal vaccination; Nanoemulsion; Vaccine