Leung Daniel T, Rahman Mohammad Arif, Mohasin M, Riyadh M Asrafuzzaman, Patel Sweta M, Alam Mohammad Murshid, Chowdhury Fahima, Khan Ashraful Islam, Kalivoda Eric J, Aktar Amena, Bhuiyan M Saruar, LaRocque Regina C, Harris Jason B, Calderwood Stephen B, Qadri Firdausi, Ryan Edward T
International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
Clin Vaccine Immunol. 2011 Aug;18(8):1317-25. doi: 10.1128/CVI.05124-11. Epub 2011 Jun 22.
Children bear a large component of the global burden of cholera. Despite this, little is known about immune responses to cholera in children, especially those under 5 years of age. Cholera vaccine studies have demonstrated lower long-term protective efficacy in young children than in older children and adults. Memory B cell (MBC) responses may correlate with duration of protection following infection and vaccination. Here we report a comparison of immune responses in young children (3 to 5 years of age; n = 17), older children (6 to 17 years of age; n = 17), and adults (18 to 60 years of age; n = 68) hospitalized with cholera in Dhaka, Bangladesh. We found that young children had lower baseline vibriocidal antibody titers and higher fold increases in titer between day 2 and day 7 than adults. Young children had higher baseline IgG plasma antibody levels to Vibrio cholerae antigens, although the magnitudes of responses at days 7 and 30 were similar across age groups. As a surrogate marker for mucosal immune responses, we assessed day 7 antibody-secreting cell (ASC) responses. These were comparable across age groups, although there was a trend for older age groups to have higher levels of lipopolysaccharide-specific IgA ASC responses. All age groups developed comparable MBC responses to V. cholerae lipopolysaccharide and cholera toxin B subunit at day 30. These findings suggest that young children are able to mount robust vibriocidal, plasma antibody, ASC, and MBC responses against V. cholerae O1, suggesting that under an optimal vaccination strategy, young children could achieve protective efficacy comparable to that induced in adults.
儿童承担着全球霍乱负担的很大一部分。尽管如此,人们对儿童尤其是5岁以下儿童对霍乱的免疫反应知之甚少。霍乱疫苗研究表明,幼儿的长期保护效力低于大龄儿童和成年人。记忆B细胞(MBC)反应可能与感染和接种疫苗后的保护持续时间相关。在此,我们报告了对孟加拉国达卡因霍乱住院的幼儿(3至5岁;n = 17)、大龄儿童(6至17岁;n = 17)和成年人(18至60岁;n = 68)的免疫反应进行的比较。我们发现,幼儿的基线杀弧菌抗体滴度较低,与成年人相比,在第2天至第7天之间滴度的倍数增加更高。幼儿针对霍乱弧菌抗原的基线IgG血浆抗体水平较高,尽管各年龄组在第7天和第30天的反应幅度相似。作为黏膜免疫反应的替代标志物,我们评估了第7天的抗体分泌细胞(ASC)反应。各年龄组的反应相当,尽管大龄组有脂多糖特异性IgA ASC反应水平较高的趋势。所有年龄组在第30天对霍乱弧菌脂多糖和霍乱毒素B亚单位产生的MBC反应相当。这些发现表明,幼儿能够针对霍乱弧菌O1产生强大的杀弧菌、血浆抗体、ASC和MBC反应,这表明在最佳疫苗接种策略下,幼儿能够获得与成年人相当的保护效力。