Oral immunization of mice with Lactococcus lactis expressing the rotavirus VP8* protein

Biotechnol Lett. 2011 Jun;33(6):1169-75. doi: 10.1007/s10529-011-0551-6. Epub 2011 Feb 8.

Abstract

The efficacy of recombinant Lactococcus lactis as a delivery vehicle for a rotavirus antigen was evaluated in a mouse model. The rotavirus VP8* protein was expressed intracellularly and extracellularly in L. lactis wild type and in an alr mutant deficient in alanine racemase activity, necessary for the synthesis of the cell-wall component D: -alanine. When the mucosal immune response was evaluated by measuring VP8*-specific IgA antibody in faeces, wild-type L. lactis triggered a low IgA synthesis only when the secreting strain was used. In contrast, VP8*-specific IgA was detected in faeces of both groups of mice orally given the alr mutant expressing extracellular VP8* and intracellular VP8*, which reached levels similar to that obtained with the wild type secreting strain. However, oral administration of the recombinant strains did not induce serum IgG or IgA responses. L. lactis cell-wall mutants may therefore provide certain advantages when low-antigenic proteins are expressed intracellularly. However, the low immune response obtained by using this antigen-bacterial host combination prompts to the use of new strains and vaccination protocols in order to develop acceptable rotavirus immunization levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Alanine Racemase / genetics
  • Alanine Racemase / metabolism
  • Animals
  • Antibodies, Viral / biosynthesis
  • Antigens, Viral / administration & dosage
  • Antigens, Viral / genetics
  • Base Sequence
  • Biotechnology
  • Female
  • Genetic Vectors
  • Immunity, Mucosal
  • Immunoglobulin A / biosynthesis
  • Lactococcus lactis / genetics*
  • Lactococcus lactis / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • Plasmids / genetics
  • RNA-Binding Proteins / administration & dosage
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / immunology*
  • Rotavirus / genetics*
  • Rotavirus / immunology*
  • Rotavirus Infections / immunology
  • Rotavirus Infections / prevention & control
  • Rotavirus Vaccines / administration & dosage*
  • Rotavirus Vaccines / genetics
  • Rotavirus Vaccines / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Nonstructural Proteins / administration & dosage
  • Viral Nonstructural Proteins / genetics*
  • Viral Nonstructural Proteins / immunology*

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Immunoglobulin A
  • RNA-Binding Proteins
  • Rotavirus Vaccines
  • Vaccines, Synthetic
  • Viral Nonstructural Proteins
  • NS35 protein, rotavirus
  • Alanine Racemase