Colonic Immune Stimulation by Targeted Oral Vaccine

Background Currently, sufficient data exist to support the use of lactobacilli as candidates for the development of new oral targeted vaccines. To this end, we have previously shown that Lactobacillus gasseri expressing the protective antigen (PA) component of anthrax toxin genetically fused to a dendritic cell (DC)-binding peptide (DCpep) induced efficacious humoral and T cell-mediated immune responses against Bacillus anthracis Sterne challenge. Methodology/Principal Finding In the present study, we investigated the effects of a dose dependent treatment of mice with L. gasseri expressing the PA-DCpep fusion protein on intestinal and systemic immune responses and confirmed its safety. Treatment of mice with different doses of L. gasseri expressing PA-DCpep stimulated colonic immune responses, resulting in the activation of innate immune cells, including dendritic cells, which induced robust Th1, Th17, CD4+Foxp3+ and CD8+Foxp3+ T cell immune responses. Notably, high doses of L. gasseri expressing PA-DCpep (1012 CFU) were not toxic to the mice. Treatment of mice with L. gasseri expressing PA-DCpep triggered phenotypic maturation and the release of proinflammatory cytokines by dendritic cells and macrophages. Moreover, treatment of mice with L. gasseri expressing PA-DCpep enhanced antibody immune responses, including IgA, IgG1, IgG2b, IgG2c and IgG3. L. gasseri expressing PA-DCpep also increased the gene expression of numerous pattern recognition receptors, including Toll-like receptors, C-type lectin receptors and NOD-like receptors. Conclusion/Significance These findings suggest that L. gasseri expressing PA-DCpep has substantial immunopotentiating properties, as it can induce humoral and T cell-mediated immune responses upon oral administration and may be used as a safe oral vaccine against anthrax challenge.

• Publication year

  2013

• Venue

  PLoS ONE

• Publication date

  2013-01-30

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0055143PMID 23383086PMCID 3559436
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Treatment increased proinflammatory cytokine release, promoted maturation of dendritic cells and macrophages, enhanced antibody immune responses, and upregulated pattern recognition receptor genes.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• The 10^12 CFU dose was not toxic to mice.

  Confidence 0.96

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• Lactobacillus gasseri expressing PA-DCpep induced Th1/Th17/Foxp3+ T cell responses.

  Confidence 0.97

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• Lactobacillus gasseri expressing PA-DCpep stimulated colonic immune responses and activated dendritic cells after oral administration.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review

• 10^12 cfu dose

  dose, treatment parameter

  The highest oral dose tested, expressed as colony-forming units administered to mice.

  Aliases: 10^12 CFU, high dose

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• antibody immune responses

  immune response, humoral response

  Humoral immune responses measured by the production of IgA and IgG subclasses.

  Aliases: humoral immune responses, antibody responses

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• colonic immune responses

  immune response, tissue response

  Immune responses measured in the colon after oral administration of the vaccine strain.

  Aliases: colonic immunity

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• dendritic cells

  immune cell, cell type

  Antigen-presenting immune cells examined for activation and maturation in response to treatment.

  Aliases: DCs

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• lactobacillus gasseri expressing pa-dcpep

  engineered strain, vaccine vector

  An engineered L. gasseri strain used as an oral vaccine carrier to deliver the PA-DCpep fusion construct.

  Aliases: PA-DCpep-expressing L. gasseri, L. gasseri expressing PA-DCpep

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• macrophages

  immune cell, cell type

  Innate immune cells assessed for maturation and cytokine-related responses after vaccination.

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• pattern recognition receptors

  receptor family, innate immune receptor

  Innate immune receptors whose gene expression was measured after treatment, including Toll-like, C-type lectin, and NOD-like receptors.

  Aliases: PRRs

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• proinflammatory cytokines

  cytokine, immune mediator

  Inflammatory signaling molecules released by immune cells after treatment.

  Aliases: proinflammatory cytokine release

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• th1/th17/foxp3+ t cell responses

  adaptive immune response, T cell response

  T cell responses characterized by Th1, Th17, CD4+Foxp3+, and CD8+Foxp3+ subsets after vaccination.

  Aliases: Th1, Th17, CD4+Foxp3+ and CD8+Foxp3+ T cell responses

  박진우 (dztg5apj7m) extractionAK (4715169a40) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review

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