Oral Administration of Lactococcus lactis Expressing Synthetic Genes of Myelin Antigens in Decreasing Experimental Autoimmune Encephalomyelitis in Rats
Kaja Kasarello, Barbara Kwiatkowska-Patzer, Andrzej W. Lipkowski, Jacek K. Bardowski, Agnieszka K. Szczepankowska
Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland
Med Sci Monit 2015; 21:1587-1597
Multiple sclerosis is a human autoimmunological disease that causes neurodegeneration. One of the potential ways to stop its development is induction of oral tolerance, whose effect lies in decreasing immune response to the fed antigen. It was shown in animal models that administration of specific epitopes of the three main myelin proteins – myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and proteolipid protein (PLP) – results in induction of oral tolerance and suppression of disease symptoms. Use of bacterial cells to produce and deliver antigens to gut mucosa seems to be an attractive method for oral tolerance induction in treatment of diseases with autoimmune background.
Material and Methods: Synthetic genes of MOG35-55, MBP85-97, and PLP139-151 myelin epitopes were generated and cloned in Lactococcus lactis under a CcpA-regulated promoter. The tolerogenic effect of bacterial preparations was tested on experimental autoimmune encephalomyelitis, which is the animal model of MS. EAE was induced in rats by intradermal injection of guinea pig spinal cord homogenate into hind paws.
Results: Rats were administered preparations containing whole-cell lysates of L. lactis producing myelin antigens using different feeding schemes. Our study demonstrates that 20-fold, but not 4-fold, intragastric administration of autoantigen-expressing L. lactis cells under specific conditions reduces the clinical symptoms of EAE in rats.
Conclusions: The present study evaluated the use of myelin antigens produced in L. lactis in inhibiting the onset of experimental autoimmune encephalomyelitis in rats. Obtained results indicate that application of such recombinant cells can be an attractive method of oral tolerance induction.
Keywords: Animals, Administration, Oral, Base Sequence, Cloning, Molecular, Encephalomyelitis, Autoimmune, Experimental - immunology, Immune Tolerance - immunology, Lactococcus lactis - metabolism, Molecular Sequence Data, Myelin Basic Protein - pharmacology, Myelin Proteolipid Protein - pharmacology, Myelin-Oligodendrocyte Glycoprotein - pharmacology, Oligonucleotides - genetics, Peptide Fragments - pharmacology, Rats, Sequence Analysis, DNA