Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters

• Published in: The Journal of clinical investigation Vol. 128; no. 9; pp. 3853 - 3865
• Main Authors: da Silva Antunes, Ricardo, Babor, Mariana, Carpenter, Chelsea, Khalil, Natalie, Cortese, Mario, Mentzer, Alexander J, Seumois, Grégory, Petro, Christopher D, Purcell, Lisa A, Vijayanand, Pandurangan, Crotty, Shane, Pulendran, Bali, Peters, Bjoern, Sette, Alessandro
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01-09-2018
• Subjects: Adolescent; Adult; Antibodies, Bacterial - blood; Antigens; Biomedical research; Bordetella pertussis - immunology; CD4 antigen; Cell activation; Child; Child, Preschool; Children; Comparative analysis; Cytokines; Cytokines - blood; Diphtheria; Female; Genomes; Granulocytes; Health aspects; Helper cells; Humans; Immune response; Immunization Schedule; Immunization, Secondary; Immunologic Memory; Immunological memory; Infant; Infections; Interleukin 13; Interleukin 17; Interleukin 4; Interleukin 5; Interleukin 9; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Male; Memory cells; Middle Aged; Pertussis; Pertussis Vaccine - administration & dosage; Pertussis Vaccine - immunology; Pertussis vaccines; Physiological aspects; Polarity (Biology); Polarization; T cell receptors; T cells; Tetanus; Th1 Cells - immunology; Th17 Cells - immunology; Transcriptome; Vaccines; Vaccines, Acellular - administration & dosage; Vaccines, Acellular - immunology; Whooping cough; Young Adult; γ-Interferon; United States > US; Th1 response; Adaptive immunity; Immunology; Vaccines; Cellular immune response
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI121309

In the mid-1990s, whole-cell pertussis (wP) vaccines were associated with local and systemic adverse events that prompted their replacement with acellular pertussis (aP) vaccines in many high-income countries. In the past decade, rates of pertussis disease have increased in children receiving only aP vaccines. We compared the immune responses to aP boosters in individuals who received their initial doses with either wP or aP vaccines using activation-induced marker (AIM) assays. Specifically, we examined pertussis-specific memory CD4+ T cell responses ex vivo, highlighting a type 2/Th2 versus type 1/Th1 and Th17 differential polarization as a function of childhood vaccination. Remarkably, after a contemporary aP booster, cells from donors originally primed with aP were (a) associated with increased IL-4, IL-5, IL-13, IL-9, and TGF-β and decreased IFN-γ and IL-17 production, (b) defective in their ex vivo capacity to expand memory cells, and (c) less capable of proliferating in vitro. These differences appeared to be T cell specific, since equivalent increases of antibody titers and plasmablasts after aP boost were seen in both groups. In conclusion, our data suggest that there are long-lasting effects and differences in polarization and proliferation of T cell responses in adults originally vaccinated with aP compared with those that initially received wP, despite repeated acellular boosters.