Immunomodulation of T(H)2 biased immunity with mucosal administration of nanoemulsion adjuvant

摘要

T(H)2-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 T(H)2-biased response, this has led to interest in developing adjuvants capable of activating T(H)1 immunity and modulating existing T(H)2 responses. Immunotherapies to shift immune responses from T(H)2 to T(H)1 have generally required prolonged immunization protocols and have not induced effective T(H)1 responses. We have demonstrated that nanoscale emulsions (NE), a novel mucosal adjuvant, induce robust IgA and IgG antibody responses and T(H)1/T(H)17 cellular immunity resulting in protection against a variety of respiratory and mucosal infections. Because intranasal (i.n.) delivery of NE adjuvant consistently induces T(H)1/T(H)17 biased responses, we hypothesized that NE could be used as a therapeutic vaccine to redirect existing T(H)2 polarized immunity towards a more balanced T(H)1/T(H)2 profile. To test this, a T(H)2 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 T(H)1 associated immune responses and IL-17, and decreased T(H)2 cytokines (IL-4 and IL-5) and IgGl. NE immunization induced regulatory T cells and IL-10, and IL-10 was required for the suppression of T(H)2 immunity. These data demonstrate that NE-based vaccines can modulate existing T(H)2 immune responses to promote T(H)1/T(H)17 immunity and suggest the potential therapeutic use of NE vaccines for diseases associated with T(H)2 immunity. (C) 2016 The Authors. Published by Elsevier Ltd.