Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

Abstract

Nasal administration of an oil-in-water nanoemulsion (NE) adjuvant W805EC produces potent systemic and mucosal, Th-1– and Th-17–balanced cellular responses. However, its molecular mechanism of action has not been fully characterized and is of particular interest because NE does not contain specific ligands for innate immune receptors. In these studies, we demonstrate that W805EC NE adjuvant activates innate immunity, induces specific gene transcription, and modulates NF-κB activity via TLR2 and TLR4 by a mechanism that appears to be distinct from typical TLR agonists. Nasal immunization with NE-based vaccine showed that the TLR2, TLR4, and MyD88 pathways and IL-12 and IL-12Rβ1 expression are not required for an Ab response, but they are essential for the induction of balanced Th-1 polarization and Th-17 cellular immunity. NE adjuvant induces MHC class II, CD80, and CD86 costimulatory molecule expression and dendritic cell maturation. Further, upon immunization with NE, adjuvant mice deficient in the CD86 receptor had normal Ab responses but significantly reduced Th-1 cellular responses, whereas animals deficient in both CD80 and CD86 or lacking CD40 failed to produce either humoral or cellular immunity. Overall, our data show that intranasal administration of Ag with NE induces TLR2 and TLR4 activation along with a MyD88-independent Ab response and a MyD88-dependent Th-1 and Th-17 cell–mediated immune response. These findings suggest that the unique properties of NE adjuvant may offer novel opportunities for understanding previously unrecognized mechanisms of immune activation important for generating effective mucosal and systemic immune responses.

Surfactin inducing mitochondria-dependent ROS to activate MAPKs, NF-κB and inflammasomes in macrophages for adjuvant activity

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Mucosal adjuvants: Opportunities and challenges

“…It has been demonstrated that MyD88 and Toll/IL-1 receptor domain-containing adaptor inducing IFN-b (TRIF), the critical signaling components for TLR, are not necessary for antibody responses. 25,26 These new findings provide new insights into development of mucosal adjuvants.…”

Dendritic cells as critical players in allergic rhinitis

“…Due to the use of adjuvants like toll-like receptor agonist and vectors like liposomes and microspheres in clinical trials, advantages were seen in Phase II and Phase III trials (52). Nasal mucosa administration of antigens in the presence of adjuvants like nano-emulsion induced distinct pathways of humoral and cellular immunity (53). CD40, CD80, and CD86 are molecules expressed by DCs that are important for a well-established immune response.…”