title: Modulation of the CD4(+) T cell response after acellular pertussis vaccination in the presence of TLR4 ligation.
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.
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. Electronic address: jolanda.brummelman@rivm.nl.
authors: Jolanda
authors: J
authors: Brummelman
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors: Kina
authors: K
authors: Helm
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors: Hendrik-Jan
authors: HJ
authors: Hamstra
authors: Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands.
authors: Peter
authors: P
authors: van der Ley
authors: Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands.
authors: Claire J P
authors: CJ
authors: Boog
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors: Wanda G H
authors: WG
authors: Han
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors: Cécile A C M
authors: CA
authors: van Els
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000302:isolation & purification*; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000276:immunology*; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007156:Immunologic Memory; D051379:Mice; D010641:Phenotype; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D007074:Immunoglobulin G; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: Acellular pertussis vaccine; Adjuvants; Bordetella pertussis; CD4 T cells; Memory T cells; TLR4