Modulation of the CD4(+) T cell response after acellular pertussis vaccination in the presence of TLR4 ligation

Vaccine. 2015 Mar 17;33(12):1483-91. doi: 10.1016/j.vaccine.2015.01.063. Epub 2015 Feb 7.

Abstract

Whole cell pertussis (wP) vaccines are gradually being replaced by aluminum salt-adjuvanted acellular pertussis (aP) vaccines. These promote CD4(+) T cell responses with a non-protective Th2 component, while protective immune mechanisms to B. pertussis may rather involve long-lived Th1/Th17 type CD4(+) T cells. Here we asked whether addition of a non-toxic meningococcal LPS derivative, LpxL1, as adjuvant can favorably modulate the aP-induced pertussis-specific CD4(+) T cell response in mice. To assess the effect of TLR4 ligation, Th type, quantity, and memory potential of pertussis-specific CD4(+) T cells were determined at the single-cell level after aP and aP+LpxL1 vaccination using intracellular cytokine staining and MHC class II tetramers. Adding LpxL1 to the aP vaccine weakened the Th2 component and strengthened the Th1/Th17 component of the specific CD4(+) T cell response. Notably, LpxL1 addition also induced higher frequencies of tetramer positive CD4(+) T cells in draining lymph nodes or blood, depending on the phase after vaccination. Moreover, there was a net profit in the number of CD4(+) T cells with a central memory phenotype, preferred for long-term immunity. Thus, adding a TLR4 ligand as adjuvant to a current aP vaccine was associated with a more favorable pertussis-specific CD4(+) T cell response.

Keywords: Acellular pertussis vaccine; Adjuvants; Bordetella pertussis; CD4 T cells; Memory T cells; TLR4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytokines / immunology
  • Cytokines / isolation & purification*
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / immunology*
  • Immunization, Secondary
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunologic Memory*
  • Mice
  • Phenotype
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Th2 Cells / immunology
  • Toll-Like Receptor 4 / immunology*

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Diphtheria-Tetanus-acellular Pertussis Vaccines
  • Immunoglobulin G
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4