Prophylactic vaccination with adjuvant monophosphoryl lipid a prevents Th2-mediated murine asthmatic responses

Abstract

Objective: Asthma is a chronic respiratory disorder characterized by airway hyperreactivity, eosinophilic infiltration, high titer of allergen-specific IgE, and overproduction of T helper 2 (Th2) cytokines. Antigen combined with an appropriate adjuvant and administrated through the proper route can elicit suitable immunological responses to protect humans and animals from diseases. Antigen formulated with monophosphoryl lipid A (MPLA) can produce priming of Th1-mediated immune responses. The purpose of this study was to examine the utility of MPLA as an adjuvant to prevent asthma.

Methods: BALB/c mice were immunized with ovalbumin (OVA) formulated with or without MPLA by intraperitoneal, footpad, or subcutaneous injection. Vaccinated mice were challenged with OVA aerosol to estimate the protective efficacy of MPLA in comparison to Th2-adjuvant aluminum hydroxide (Alum). Airway hyperresponsiveness to methacholine, eosinophilia in bronchoalveolar lavage fluid (BALF), circulating titers of OVA-specific antibodies, and stimulating levels of IFN-γ and IL-4 cytokines from splenocytes were evaluated.

Results: Mice immunized by all injection routes with OVA formulated with MPLA increased the ratio of Th1/Th2 responses compared to mice receiving antigen alone. For prophylactic vaccination purpose, MPLA reduced airway responsiveness and eosinophilic inflammation in the lung, decreased serum OVA-specific IgE level, and increased the serum ratio of OVA-specific IgG2a/IgG1 and the ratio of IFN-γ/IL4 from OVA-activated splenocytes compared with mice vaccinated with Alum.

Conclusion: MPLA may be clinically useful in the vaccination of individuals predisposed to asthma.