Oral Vaccination With Lipid-Formulated BCG Induces a Long-Lived, Multifunctional CD4(+) T Cell Memory Immune Response

PLoS One. 2012;7(9):e45888. doi: 10.1371/journal.pone.0045888. Epub 2012 Sep 25.

Abstract

Oral delivery of BCG in a lipid formulation (Liporale™-BCG) targets delivery of viable bacilli to the mesenteric lymph nodes and confers protection against an aerosol Mycobacterium tuberculosis challenge. The magnitude, quality and duration of the effector and memory immune response induced by Liporale™-BCG vaccination is unknown. Therefore, we compared the effector and memory CD4(+) T cell response in the spleen and lungs of mice vaccinated with Liporale™-BCG to the response induced by subcutaneous BCG vaccination. Liporale™-BCG vaccination induced a long-lived CD4(+) T cell response, evident by the detection of effector CD4(+) T cells in the lungs and a significant increase in the number of Ag85B tetramer-specific CD4(+) T cells in the spleen up to 30 weeks post vaccination. Moreover, following polyclonal stimulation, Liporale™-BCG vaccination, but not s.c. BCG vaccination, induced a significant increase in both the percentage of CD4(+) T cells in the lungs capable of producing IFNγ and the number of multifunctional CD4(+) T cells in the lungs at 30 weeks post vaccination. These results demonstrate that orally delivered Liporale™-BCG vaccine induces a long-lived multifunctional immune response, and could therefore represent a practical and effective means of delivering novel BCG-based TB vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / chemistry
  • Administration, Oral
  • Animals
  • Antigens, Bacterial / chemistry
  • BCG Vaccine / therapeutic use*
  • Bacterial Proteins / chemistry
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • Immune System
  • Interferon-gamma / metabolism
  • Lipids / chemistry
  • Lung / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / metabolism
  • Spleen / cytology
  • Vaccines / therapeutic use*

Substances

  • Antigens, Bacterial
  • BCG Vaccine
  • Bacterial Proteins
  • Lipids
  • Vaccines
  • Interferon-gamma
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis

Grant support

Financial support was recieved through the Wellington Medical Research Foundation Malaghan Haematology Fellowship (JRK), the University of Otago (LRA), and Otago Innovations Ltd (FEA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.