Immunomodulation of TH2 biased immunity with mucosal administration of nanoemulsion adjuvant

Autor: Anna U. Bielinska, Jessica J. O’Konek, James R. Baker, Katarzyna W. Janczak
Jazyk: angličtina
Předmět:
0301 basic medicine
Immunoglobulin A
Cellular immunity
medicine.medical_treatment
animal diseases
Immunoglobulin G
Mice
0302 clinical medicine
Nanoemulsion
Adjuvant
Immunity
Cellular
biology
Immunogenicity
ELISA
enzyme-linked immunosorbent assay
i.p.
intraperitoneal
Infectious Diseases
cLN
cervical lymph node
Molecular Medicine
Cytokines
Emulsions
Female
ova
ovalbumin
Intranasal vaccination
Treg
regulatory T cell
chemical and pharmacologic phenomena
Article
03 medical and health sciences
Immune system
Th2 Cells
Adjuvants
Immunologic
NE
nanoemulsion
Immunity
Immunology and Microbiology(all)
medicine
Animals
Immunity
Mucosal
Administration
Intranasal
Hepatitis B Surface Antigens
General Veterinary
General Immunology and Microbiology
business.industry
Public Health
Environmental and Occupational Health
i.n.
intranasal
Th1 Cells
biochemical phenomena
metabolism
and nutrition
veterinary(all)
Immunity
Humoral
Nanostructures
HBs
hepatitis B surface antigen
030104 developmental biology
Immunization
i.m.
intramuscular
Immunology
biology.protein
alum
aluminum hydroxide
Th17 Cells
bacteria
business
Vaccine
030215 immunology
Zdroj: Vaccine
ISSN: 0264-410X
DOI: 10.1016/j.vaccine.2016.06.043
Popis: Highlights • Nanoemulsion vaccine adjuvant induces robust antigen specific TH1-biased immunity. • Nanoemulsion vaccine adjuvant suppresses established TH2 immunity. • Efficacy of nanoemulsion vaccine in mice with pre-existing immunity to same antigen. • Nanoemulsion vaccines induce IL-10 and regulatory T cells.
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.
Databáze: OpenAIRE
Externí odkaz: