Leung Daniel T, Rahman Mohammad Arif, Mohasin M, Patel Sweta M, Aktar Amena, Khanam Farhana, Uddin Taher, Riyadh M Asrafuzzaman, Saha Amit, Alam Mohammad Murshid, Chowdhury Fahima, Khan Ashraful Islam, Charles Richelle, LaRocque Regina, Harris Jason B, Calderwood Stephen B, Qadri Firdausi, Ryan Edward T
Centre for Vaccine Sciences, Bangladesh, Dhaka, Bangladesh.
Clin Vaccine Immunol. 2012 May;19(5):690-8. doi: 10.1128/CVI.05615-11. Epub 2012 Mar 21.
Current oral cholera vaccines induce lower protective efficacy and shorter duration of protection against cholera than wild-type infection provides, and this difference is most pronounced in young children. Despite this, there are limited data comparing immune responses in children following wild-type disease versus vaccination, especially with regard to memory responses associated with long-term immunity. Here, we report a comparison of immune responses in young children (2 to 5 years of age; n = 20) and older children (6 to 17 years of age; n = 20) given two doses of an oral killed cholera vaccine containing recombinant cholera toxin B subunit (CtxB) 14 days apart and compare these responses to those induced in similarly aged children recovering from infection with Vibrio cholerae O1 Ogawa in Bangladesh. We found that the two vaccine groups had comparable vibriocidal and lipopolysaccharide (LPS)-specific plasma antibody responses. Vaccinees developed lower levels of IgG memory B cell (MBC) responses against CtxB but no significant MBC responses against LPS. In contrast, children recovering from natural cholera infection developed prominent LPS IgG and IgA MBC responses, as well as CtxB IgG MBC responses. Plasma LPS IgG, IgA, and IgM responses, as well as vibriocidal responses, were also significantly higher in children following disease than after vaccination. Our findings suggest that acute and memory immune responses following oral cholera vaccination in children are significantly lower than those observed following wild-type disease, especially responses targeting LPS. These findings may explain, in part, the lower efficacy of oral cholera vaccination in children.
与野生型感染相比,目前的口服霍乱疫苗诱导的霍乱保护效力较低,保护持续时间较短,这种差异在幼儿中最为明显。尽管如此,比较野生型疾病患儿与接种疫苗患儿免疫反应的数据有限,尤其是与长期免疫相关的记忆反应方面。在此,我们报告了对2至5岁幼儿(n = 20)和6至17岁大龄儿童(n = 20)给予两剂间隔14天的含重组霍乱毒素B亚单位(CtxB)的口服灭活霍乱疫苗后的免疫反应进行比较,并将这些反应与在孟加拉国从霍乱弧菌O1小川型感染中康复的同龄儿童所诱导的反应进行比较。我们发现,两个疫苗组的杀弧菌和脂多糖(LPS)特异性血浆抗体反应相当。接种疫苗者针对CtxB产生的IgG记忆B细胞(MBC)反应水平较低,但针对LPS没有显著的MBC反应。相比之下,从自然霍乱感染中康复的儿童产生了显著的LPS IgG和IgA MBC反应,以及CtxB IgG MBC反应。疾病患儿的血浆LPS IgG、IgA和IgM反应以及杀弧菌反应也显著高于接种疫苗后。我们的研究结果表明,儿童口服霍乱疫苗后的急性和记忆免疫反应明显低于野生型疾病后的反应,尤其是针对LPS的反应。这些发现可能部分解释了口服霍乱疫苗在儿童中效力较低的原因。