Unlipidated Outer Membrane Protein Omp16 (U-Omp16) from Brucella spp. as Nasal Adjuvant Induces a Th1 Immune Response and Modulates the Th2 Allergic Response to Cow’s Milk Proteins

Andrés E Ibañez,Gabriela S Risso,Lorena M Coria,Sergio C Oliveira,Paola Smaldini,Karina A Pasquevich,Guillermo H Docena,Juliana Cassataro,Carlos Alberto Fossati,Guillermo H Giambartolomei,María V Delpino,Lucila G G Pacífico,Eliane Namie Miyaji

doi:10.1371/journal.pone.0069438

Abstract

The discovery of novel mucosal adjuvants will help to develop new formulations to control infectious and allergic diseases. In this work we demonstrate that U-Omp16 from Brucella spp. delivered by the nasal route (i.n.) induced an inflammatory immune response in bronchoalveolar lavage (BAL) and lung tissues. Nasal co-administration of U-Omp16 with the model antigen (Ag) ovalbumin (OVA) increased the amount of Ag in lung tissues and induced OVA-specific systemic IgG and T helper (Th) 1 immune responses. The usefulness of U-Omp16 was also assessed in a mouse model of food allergy. U-Omp16 i.n. administration during sensitization ameliorated the hypersensitivity responses of sensitized mice upon oral exposure to Cow’s Milk Protein (CMP), decreased clinical signs, reduced anti-CMP IgE serum antibodies and modulated the Th2 response in favor of Th1 immunity. Thus, U-Omp16 could be used as a broad Th1 mucosal adjuvant for different Ag formulations.

Highlights

The main function of the mucosa is to maintain normal physiology while discriminating between dangerous and innocuous proteins or organisms [1]
We studied the recruitment of macrophages, neutrophils and lymphocytes to bronchoalveolar lavage (BAL) after nasal delivery of UOmp16 or PBS as control
In a previous work we discovered that Unlipidated Outer Membrane Protein Omp16 (U-Omp16) from Brucella is a new pathogen associated molecular pattern (PAMP) that signals through TLR4 and has self-adjuvanting properties when delivered either parenterally or orally [16]

Summary

Introduction

The main function of the mucosa is to maintain normal physiology while discriminating between dangerous and innocuous proteins or organisms [1]. The induction of mucosal immune responses is of paramount importance in both health and disease. Vaccination through the mucosal route is an interesting strategy for antigen (Ag) administration because it is not associated with pain or stress, and its administration is very easy and cost-efficient. Induction of immune responses following mucosal immunization -using non-live vaccines-is usually dependent upon the co-administration of appropriate adjuvants that can initiate and support the transition from innate to adaptive immunity [2]. An adjuvant is a vaccine component that, through its capacity to act as an immunomodulator/immunostimulant induces and/or enhances an immune response against codelivered Ags. While there are many types of adjuvants, not all of them are effective at promoting mucosal immune responses

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Conclusion