A multi-epitope plant-made chimeric protein (LTBentero) targeting common enteric pathogens is immunogenic in mice

Plant Mol Biol. 2020 Jan;102(1-2):159-169. doi: 10.1007/s11103-019-00938-3. Epub 2019 Dec 10.

Abstract

A plant-based multiepitopic protein (LTBentero) containing epitopes from ETEC, S. typhimurium, and V. parahaemolyticus was produced in plants cells and triggered systemic and intestinal humoral responses in immunized mice. Around 200 million people suffer gastroenteritis daily and more than 2 million people die annually in developing countries due to such pathologies. Vaccination is an alternative to control this global health issue, however new low-cost vaccines are needed to ensure proper vaccine coverage. In this context, plants are attractive hosts for the synthesis and delivery of subunit vaccines. Therefore, in this study a plant-made multiepitopic protein named LTBentero containing epitopes from antigens of enterotoxigenic E. coli, S. typhimurium, and V. parahaemolyticus was produced and found immunogenic in mice. The LTBentero protein was expressed in tobacco plants at up to 5.29 µg g-1 fresh leaf tissue and was deemed immunogenic when administered to BALB/c mice either orally or subcutaneously. The plant-made LTBentero antigen induced specific IgG (systemic) and IgA (mucosal) responses against LTB, ST, and LptD epitopes. In conclusion, multiepitopic LTBentero was functionally produced in plant cells, being capable to trigger systemic and intestinal humoral responses and thus it constitutes a promising oral immunogen candidate in the fight against enteric diseases.

Keywords: Antibody response; Enteric diseases; Multiepitopic; Plant-based vaccine; Recombinant protein.

MeSH terms

  • Animals
  • Antibodies, Bacterial / immunology
  • Bacterial Toxins / genetics
  • Bacterial Toxins / immunology*
  • Bacterial Vaccines / immunology
  • Enterotoxigenic Escherichia coli / genetics
  • Enterotoxigenic Escherichia coli / immunology
  • Epitopes / genetics
  • Epitopes / immunology*
  • Female
  • Gene Expression Regulation, Plant
  • Immunization*
  • Immunoglobulin A
  • Immunoglobulin G
  • Mice
  • Mice, Inbred BALB C
  • Mucous Membrane / immunology
  • Nicotiana / genetics
  • Plant Proteins / genetics
  • Plant Proteins / immunology*
  • Plant Proteins / metabolism
  • Plants, Genetically Modified / genetics
  • Plants, Genetically Modified / immunology
  • Plants, Genetically Modified / metabolism
  • Recombinant Proteins / immunology*
  • Recombinant Proteins / metabolism
  • Vaccination
  • Vaccines, Edible / genetics
  • Vaccines, Edible / immunology*

Substances

  • Antibodies, Bacterial
  • Bacterial Toxins
  • Bacterial Vaccines
  • Epitopes
  • Immunoglobulin A
  • Immunoglobulin G
  • Plant Proteins
  • Recombinant Proteins
  • Vaccines, Edible