Immune response elicited by DNA vaccination using Lactococcus lactis is modified by the production of surface exposed pathogenic protein

PLoS One. 2014 Jan 21;9(1):e84509. doi: 10.1371/journal.pone.0084509. eCollection 2014.

Abstract

In this study, we compared immune responses elicited by DNA immunization using Lactococcus lactis or L. lactis expressing the Staphylococcus aureus invasin Fibronectin Binding Protein A (FnBPA) at its surface. Both strains carried pValac:BLG, a plasmid containing the cDNA of Beta-Lactoglobulin (BLG), and were designated LL-BLG and LL-FnBPA+ BLG respectively. A TH2 immune response characterized by the secretion of IL-4 and IL-5 in medium of BLG reactivated splenocytes was detected after either oral or intranasal administration of LL-FnBPA+ BLG. In contrast, intranasal administration of LL-BLG elicited a TH1 immune response. After BLG sensitization, mice previously intranasally administered with LL-BLG showed a significantly lower concentration of BLG-specific IgE than the mice non-administered. Altenatively administration of LL-FnBPA+ BLG didn't modify the BLG-specific IgE concentration obtained after sensitization, thus confirming the TH2 orientation of the immune response. To determine if the TH2-skewed immune response obtained with LL-FnBpA+ BLG was FnBPA-specific or not, mice received another L. lactis strain producing a mutated form of the Listeria monocytogenes invasin Internalin A intranasally, allowing thus the binding to murine E-cadherin, and containing pValac:BLG (LL-mInlA+ BLG). As with LL-FnBPA+ BLG, LL-mInlA+ BLG was not able to elicit a TH1 immune response. Furthermore, we observed that these difference were not due to the peptidoglycan composition of the cell wall as LL-FnBPA+ BLG, LL-mInlA+ BLG and LL-BLG strains shared a similar composition. DNA vaccination using LL-BLG elicited a pro-inflammatory TH1 immune response while using LL-FnBPA+ BLG or LL-mInlA+ BLG elicited an anti-inflammatory TH2 immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / immunology
  • Administration, Intranasal
  • Administration, Oral
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology
  • Cell Engineering
  • Drug Delivery Systems / methods
  • Female
  • Immunity, Active
  • Immunity, Cellular*
  • Lactococcus lactis / genetics*
  • Lactococcus lactis / immunology
  • Lactoglobulins / genetics
  • Lactoglobulins / immunology
  • Listeriosis / immunology
  • Listeriosis / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Plasmids
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / prevention & control*
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th2 Cells / cytology
  • Th2 Cells / immunology
  • Vaccination
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / biosynthesis
  • Vaccines, DNA / genetics
  • Vaccines, Synthetic

Substances

  • Adhesins, Bacterial
  • Bacterial Proteins
  • Lactoglobulins
  • Vaccines, DNA
  • Vaccines, Synthetic
  • fibronectin-binding proteins, bacterial
  • internalin protein, Bacteria

Grants and funding

Silvia Innocentin was a recipient of a European Marie Curie Ph.D grant from the LABHEALTH program (MEST-CT-2004-514428). Daniela Pontes was a recipient of grants from the French-Brazilian CAPES COFECUB project n°539/06 and from Region Ile de France DIM ASTREA. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n°215553-2. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.