Induction of systemic antifimbria and antitoxin antibody responses in Egyptian children and adults by an oral, killed enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine.

Induction of systemic antifimbria and antitoxin antibody responses in Egyptian children and adults by an oral, killed enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine.
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通过口服灭活产肠毒素大肠杆菌加霍乱毒素 B 亚单位疫苗,在埃及儿童和成人中诱导全身抗菌毛和抗毒素抗体反应。

DOI:
10.1128/iai.69.5.2853-2857.2001
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发表时间:
2001
影响因子:
3.1
通讯作者:
Savarino,SJ
Savarino,SJ
中科院分区:
医学2区
文献类型:
--
作者:
Hall,ER;Wierzba,TF;Ahrén,C;Rao,MR;Bassily,S;Francis,W;Girgis,FY;Safwat,M;Lee,YJ;Svennerholm,AM;Clemens,JD;Savarino,SJ

文献摘要

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我们评估了73名埃及成年人、105名学童和93名学龄前儿童对口服灭活全细胞肠毒素大肠杆菌加霍乱毒素B亚单位(ETEC-rCTB)疫苗的血清学反应。每名受试者接受两剂疫苗或安慰剂,间隔2周,在免疫前和每次接种后7天采血。采用酶联免疫吸附试验测定血浆抗rCTB抗体和4种疫苗共享定植因子(CF)。在所有受试者中测量rCTB和CFA/I的免疫球蛋白A(伊加)抗体,并在所有儿童加上33名成人的子集中测量CS 1,CS2和CS4的抗体。在每个队列中的30至33名受试者的子集中测量针对这五种抗原的IgG抗体。血清转化定义为接种后滴度增加>2倍。在94%至95%的成人接种者中观察到rCTB的伊加和IgG血清转化,滴度增加与先前报告的这两个儿科队列一样稳健。接种疫苗的儿童(范围,70 - 96%)和成人(31 - 69%)中显示对每种CF抗原的伊加血清转化的比例,以及儿童(44 - 75%)和成人(25 - 81%)中的IgG血清转化,显著高于安慰剂接受者中的相应比例,成人中对CS2的伊加应答除外。伊加抗CF滴度在儿童中一次剂量后达到峰值,而在所有年龄组中,IgG抗体在每次剂量后递增。独立地,免疫前伊加滴度和年龄与伊加反应的幅度呈负相关。总之,对ETEC-rCTB疫苗的血清学应答可作为ETEC流行地区未来儿科试验的实用免疫结局指标。
We assessed serologic responses to an oral, killed whole-cell enterotoxigenicEscherichia coliplus cholera toxin B-subunit (ETEC-rCTB) vaccine in 73 Egyptian adults, 105 schoolchildren, and 93 preschool children. Each subject received two doses of vaccine or placebo 2 weeks apart, giving blood before immunization and 7 days after each dose. Plasma antibodies to rCTB and four vaccine-shared colonization factors (CFs) were measured by enzyme-linked immunosorbent assay. Immunoglobulin A (IgA) antibodies to rCTB and CFA/I were measured in all subjects, and those against CS1, CS2, and CS4 were measured in all children plus a subset of 33 adults. IgG antibodies to these five antigens were measured in a subset of 30 to 33 subjects in each cohort. Seroconversion was defined as a >2-fold increase in titer after vaccination. IgA and IgG seroconversion to rCTB was observed in 94 to 95% of adult vaccinees, with titer increases as robust as those previously reported for these two pediatric cohorts. The proportion showing IgA seroconversion to each CF antigen among vaccinated children (range, 70 to 96%) and adults (31 to 69%), as well as IgG seroconversion in children (44 to 75%) and adults (25 to 81%), was significantly higher than the corresponding proportion in placebo recipients, except for IgA responses to CS2 in adults. IgA anti-CF titers peaked after one dose in children, whereas in all age groups IgG antibodies rose incrementally after each dose. Independently, both preimmunization IgA titer and age were inversely related to the magnitude of IgA responses. In conclusion, serologic responses to the ETEC-rCTB vaccine may serve as practical immune outcome measures in future pediatric trials in areas where ETEC is endemic.