Immunization with Haemophilus influenzae type b-CRM197 conjugate vaccine elicits a mixed Th1 and Th2CD4+ T cell cytokine response that correlates with the isotype of antipolysaccharide antibody

Immunization with Haemophilus influenzae type b-CRM197 conjugate vaccine elicits a mixed Th1 and Th2CD4+ T cell cytokine response that correlates with the isotype of antipolysaccharide antibody
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DOI:
10.1086/323342
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发表时间:
2001-10-01
影响因子:
6.4
通讯作者:
Schreiber, JR
Schreiber, JR
中科院分区:
医学2区
文献类型:
--
作者:
Kamboj, KK;King, CL;Schreiber, JR

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b型流感嗜血杆菌(Hib)荚膜多糖(PS)诱导保护性抗体,但不依赖T,婴儿免疫原性差。与蛋白质(如CRM197)结合的Hib PS结合疫苗可增加PS抗体滴度并引发免疫记忆。为了确定结合物诱导的记忆T细胞反应,19名成人接种Hib-CRM197,并测量抗体滴度、载体蛋白特异性CD4(+) T细胞增殖和细胞因子产生。Hib-CRM197诱导了PS和CRM197抗体,强烈的T细胞召回反应和细胞因子的产生,包括白细胞介素(IL)-2、IL-5、IL-10和干扰素- γ。尽管crm197特异性回忆反应性与IgM和IgA PS抗体滴度峰值相关,但PS抗体滴度存在显著的可变性。IL-2和IL-5与IgA PS抗体水平也存在相关性。Hib-CRM197诱导了crm197特异性记忆T细胞和混合Th1/Th2细胞因子的快速增加,这可能调节了PS抗体的同型和数量。
Haemophilus influenzae type b (Hib) capsular polysaccharide (PS) induces protective antibodies but is T independent and poorly immunogenic in infants. Conjugate vaccines of Hib PS linked to proteins, such as CRM197, increase the PS antibody titer and elicit immunologic memory. To define the conjugate-induced memory T cell response, 19 adults were immunized with Hib-CRM197, and antibody titers, carrier protein-specific CD4(+) T cell proliferation, and cytokine production were measured. Hib-CRM197 induced PS and CRM197 antibodies, vigorous T cell recall responses, and production of cytokines, including interleukin (IL)-2, IL-5,IL-10, and interferon-gamma. There was marked variability in PS antibody titer, despite consistent CRM197-specific recall responsiveness, which correlated with peak IgM and IgA PS antibody titers. Correlations were also found between IL-2 and IL-5 and IgA PS antibody levels. Hib-CRM197 induced a rapid increase in CRM197-specific memory T cells and mixed Th1/Th2 cytokines, which may regulate the isotype and quantity of PS antibody.