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

PLoS One. 2013 Jul 5;8(7):e69438. doi: 10.1371/journal.pone.0069438. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic* / administration & dosage
  • Animals
  • Antigens / immunology
  • Antigens / metabolism
  • Bacterial Outer Membrane Proteins / administration & dosage
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / immunology*
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Brucella / immunology*
  • Cattle
  • Central Nervous System / immunology
  • Central Nervous System / pathology
  • Cytokines / biosynthesis
  • Disease Models, Animal
  • Female
  • Immunoglobulin E / immunology
  • Immunoglobulin G / immunology
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Milk Hypersensitivity / immunology*
  • Milk Hypersensitivity / metabolism
  • Milk Proteins / immunology*
  • Nasal Mucosa / immunology
  • Nasal Mucosa / metabolism
  • Spleen / immunology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism

Substances

  • Adjuvants, Immunologic
  • Antigens
  • Bacterial Outer Membrane Proteins
  • Cytokines
  • Immunoglobulin G
  • Milk Proteins
  • Immunoglobulin E

Grants and funding

This work was supported by grants from the Bill and Melinda Gates Foundation through the Grand Challenges Explorations Initiative; from the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT-Argentina): PICT 2010 Nº 1163, PICT 2006 N° 1670, ANPCyT/CNPq PICT 2008 N° 18 and from the Universidad de Buenos Aires: (to JC); and PICT 2004 N° 25417 and PICT 2008 N° 2202 (to GD). This work was also supported by grants from CNPq/Prosul#490485/2007-3, CNPq/ANPCyT# 490528/2008-2, and INCT/Vacinas (to SCO). The funders had no role in experimental design, data collection and analysis, decision to publish, or preparation of the manuscript.