A system-view of Bordetella pertussis booster vaccine responses in adults primed with whole-cell versus acellular vaccine in infancy

被引:16
作者
Antunes, Ricardo da Silva [1 ]
Soldevila, Ferran [1 ]
Pomaznoy, Mikhail [1 ]
Babor, Mariana [1 ]
Bennett, Jason [1 ]
Tian, Yuan [1 ]
Khalil, Natalie [1 ]
Qian, Yu [2 ]
Mandava, Aishwarya [2 ]
Scheuermann, Richard H. [2 ,3 ]
Cortese, Mario [4 ]
Pulendran, Bali [4 ]
Petro, Christopher D. [5 ]
Gilkes, Adrienne P. [5 ]
Purcell, Lisa A. [5 ]
Sette, Alessandro [1 ,5 ]
Peters, Bjoern [1 ,3 ]
机构
[1] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USA
[2] J Craig Venter Inst, La Jolla, CA USA
[3] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA
[4] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA
[5] Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA
关键词
SEASONAL INFLUENZA; EPIDEMIC PERTUSSIS; IMMUNE-RESPONSES; CONTROLLED-TRIAL; IDENTIFICATION; INFECTION; DISEASE; LIGHT; SUSCEPTIBILITY; IMMUNIZATION;
D O I
10.1172/jci.insight.141023
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
The increased incidence of whooping cough worldwide suggests that current vaccination against Bordetella pertussis infection has limitations in quality and duration of protection. The resurgence of infection has been linked to the introduction of acellular vaccines (aP), which have an improved safety profile compared with the previously used whole-cell (wP) vaccines. To determine immunological differences between aP and wP priming in infancy, we performed a systems approach of the immune response to booster vaccination. Transcriptomic, proteomic, cytometric, and serologic profiling revealed multiple shared immune responses with different kinetics across cohorts, including an increase of blood monocyte frequencies and strong antigen-specific IgG responses. Additionally, we found a prominent subset of aP-primed individuals (30%) with a strong differential signature, including higher levels of expression for CCL3, NFKBIA, and ICAM1. Contrary to the wP individuals, this subset displayed increased PT-specific IgE responses after boost and higher antigen-specific IgG4 and IgG3 antibodies against FHA and FIM2/3 at baseline and after boost. Overall, the results show that, while broad immune response patterns to Tdap boost overlap between aP- and wP-primed individuals, a subset of aP-primed individuals present a divergent response. These findings provide candidate targets to study the causes and correlates of waning immunity after aP vaccination.
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页数:17
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