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

被引:93
作者
Antunes, Ricardo da Silva [1 ]
Babor, Mariana [1 ]
Carpenter, Chelsea [1 ]
Khalil, Natalie [1 ]
Cortese, Mario [2 ]
Mentzer, Alexander J. [3 ]
Seumois, Gregory [1 ]
Petro, Christopher D. [4 ]
Purcell, Lisa A. [4 ]
Vijayanand, Pandurangan [1 ,5 ]
Crotty, Shane [1 ,5 ]
Pulendran, Bali [2 ]
Peters, Bjoern [1 ,5 ]
Sette, Alessandro [1 ,5 ]
机构
[1] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USA
[2] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA
[3] Univ Oxford, Wellcome Ctr Human Genet, Oxford, England
[4] Regeneron Pharmaceut Inc, Tarrytown, NY USA
[5] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA
关键词
MEMORY T-CELLS; BORDETELLA-PERTUSSIS; IMMUNE-RESPONSES; TGF-BETA; SEROLOGICAL RESPONSES; ANTIBODY-RESPONSE; IN-VITRO; VACCINES; INFECTION; DIPHTHERIA;
D O I
10.1172/JCI121309
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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-beta and decreased IFN-gamma 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.
引用
收藏
页码:3853 / 3865
页数:13
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