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

• DOI: 10.1016/j.vaccine.2015.01.063
• Publication Date: 2015-02-07T18:47:46Z
• Authors: Jolanda Brummelman; Kina Helm; Hendrik-Jan Hamstra; Peter van der Ley; Claire J.P. Boog; Wanda G.H. Han; Cécile A.C.M. van...
• Keywords: Acellular pertussis vaccine; CD4-Positive T-Lymphocytes; 0301 basic medicine; CD4 T cells; Immunization, Secondary; Th1 Cells; Diphtheria-Tetanus-acellular Pertussis Vaccines; Memory T cells; Bordetella pertussis; 3. Good health; Toll-Like Receptor 4; Mice; 03 medical and health sciences; Phenotype; Th2 Cells; Adjuvants, Immunologic; Immunoglobulin G; Animals; Cytokines; Th17 Cells; Adjuvants; TLR4; Immunologic Memory

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.