Characterization of a Lactococcus lactis strain that secretes a major epitope of bovine beta-lactoglobulin and evaluation of its immunogenicity in mice

Appl Environ Microbiol. 2003 Nov;69(11):6620-7. doi: 10.1128/AEM.69.11.6620-6627.2003.

Abstract

Bovine beta-lactoglobulin (Blg) is one of the major cow's milk allergens. Peptide 41-60 of Blg (Blg41-60) was described as a murine T-cell determinant and a murine, rat, and human immunoglobulin E (IgE) epitope. The aim of this study was the expression of Blg41-60 as a fusion protein in the food-grade bacterium Lactococcus lactis and the characterization of its immunogenicity in mice. We constructed a recombinant strain of L. lactis capable of inducible production and secretion of Blg41-60::Nuc, a fusion protein between Blg41-60 and the mature part of the staphylococcal nuclease (Nuc). The highest production yield of Blg41-60::Nuc (32.5 mg/liter) was reached 4 h after induction. At this time, up to 75% of Blg41-60::Nuc was secreted. When monoclonal antibodies specific for Blg41-60 were used, purified Blg41-60::Nuc and synthetic Blg41-60 exhibited very similar immunoreactivities. Subcutaneous coadministration of purified Blg41-60::Nuc and killed nonrecombinant L. lactis resulted in the induction of specific anti-Blg41-60 IgG2a and IgG1. The IgG1/IgG2a ratio and the lack of specific IgE suggest a Th1-type immune response, i.e., a nonallergic response. Similar administrations of the killed Blg41-60::Nuc-producing L. lactis strain did not elicit a specific immune response, whereas a transitory mucosal IgA-specific immune response was induced in mice after oral administration of the live Blg41-60::Nuc-producing L. lactis strain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / immunology
  • Cattle
  • Epitopes / immunology
  • Epitopes / metabolism*
  • Immunity, Mucosal
  • Immunoglobulin A, Secretory / biosynthesis
  • Injections, Subcutaneous
  • Lactococcus lactis / genetics
  • Lactococcus lactis / immunology*
  • Lactoglobulins / genetics
  • Lactoglobulins / immunology
  • Lactoglobulins / metabolism*
  • Mice
  • Micrococcal Nuclease / genetics
  • Micrococcal Nuclease / immunology
  • Micrococcal Nuclease / metabolism*
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism*

Substances

  • Antibodies, Monoclonal
  • Epitopes
  • Immunoglobulin A, Secretory
  • Lactoglobulins
  • Recombinant Fusion Proteins
  • Micrococcal Nuclease