关键词: Dukoral O-specific polysaccharide antibody secreting cells vibriocidal assay

Mesh : Adult Child Humans Adolescent Child, Preschool Aged Infant, Newborn Cholera Vaccines Cholera / prevention & control Cholera Toxin O Antigens Vibrio cholerae O1 Immunoglobulin M Antibodies, Bacterial Immunoglobulin A Vaccination Antibody Formation Immunoglobulin G

来  源:   DOI:10.1128/msphere.00565-23   PDF(Pubmed)

Abstract:
Vaccination is important to prevent cholera. There are limited data comparing anti-O-specific polysaccharide (OSP) and anti-cholera toxin-specific immune responses following oral whole-cell with cholera toxin B-subunit (WC-rBS) vaccine (Dukoral, Valneva) administration in different age groups. An understanding of the differences is relevant because young children are less well protected by oral cholera vaccines than older children and adults. We compared responses in 50 adults and 49 children (ages 2 to <18) who were administered two doses of WC-rBS at a standard 14-day interval. All age groups had significant IgA and IgG plasma-blast responses to the OSP and cholera toxin B-subunit (CtxB) antigens that peaked 7 days after vaccination. However, in adults and older children (ages 5 to <18), antibody responses directed at the OSP antigen were largely IgA and IgG, with a minimal IgM response, while younger children (ages 2 to <5) mounted significant increases in IgM with minimal increases in IgA and IgG antibody responses 30 days after vaccination. In adults, anti-OSP and CtxB memory B-cell responses were detected after completion of the vaccination series, while children only mounted CtxB-specific IgG memory B-cell responses and no OSP-memory B-cell responses. In summary, children and adults living in a cholera endemic area mounted different responses to the WC-rBS vaccine, which may be a result of more prior exposure to Vibrio cholerae in older participants. The absence of class-switched antibody responses and memory B-cell responses to OSP may explain why protection wanes more rapidly after vaccination in young children compared to older vaccinees.IMPORTANCEVaccination is an important strategy to prevent cholera. Though immune responses targeting the OSP of V. cholerae are believed to mediate protection against cholera, there are limited data on anti-OSP responses after vaccination in different age groups, which is important as young children are not well protected by current oral cholera vaccines. In this study, we found that adults mounted memory B-cell responses to OSP, which were not seen in children. Adults and older children mounted class-switched (IgG and IgA) serum antibody responses to OSP, which were not seen in young children who had only IgM responses to OSP. The lack of class-switched antibody responses and memory B-cell responses to OSP in younger participants may be due to lack of prior exposure to V. cholerae and could explain why protection wanes more rapidly after vaccination in young children.
摘要:
接种疫苗对预防霍乱很重要。口服全细胞与霍乱毒素B亚基(WC-rBS)疫苗(Dukoral,Valneva)在不同年龄段的给药。对差异的理解是相关的,因为与年龄较大的儿童和成人相比,幼儿口服霍乱疫苗的保护效果较差。我们比较了50名成人和49名儿童(2至<18岁)的反应,他们在标准的14天间隔内服用了两剂WC-rBS。所有年龄组对OSP和霍乱毒素B亚基(CtxB)抗原均有显着的IgA和IgG血浆激波反应,在疫苗接种后7天达到峰值。然而,成人和年龄较大的儿童(5至<18岁),针对OSP抗原的抗体反应主要是IgA和IgG,具有最小的IgM反应,而年龄较小的儿童(2至<5岁)在接种疫苗后30天,IgM显着增加,而IgA和IgG抗体应答的增加最小。在成年人中,在完成一系列疫苗接种后检测到抗OSP和CtxtB记忆B细胞反应,而儿童仅安装了CtxtB特异性IgG记忆B细胞反应,而没有OSP记忆B细胞反应。总之,生活在霍乱流行地区的儿童和成人对WC-rBS疫苗的反应不同,这可能是老年参与者先前接触霍乱弧菌更多的结果。缺乏类别转换抗体反应和对OSP的记忆B细胞反应可能解释了为什么与年龄较大的疫苗接种者相比,接种疫苗后保护作用的减弱速度更快。重要疫苗接种是预防霍乱的重要策略。尽管针对霍乱弧菌OSP的免疫反应被认为是介导对霍乱的保护作用,不同年龄组疫苗接种后的抗OSP反应数据有限,这很重要,因为目前的口服霍乱疫苗不能很好地保护幼儿。在这项研究中,我们发现成年人对OSP产生记忆B细胞反应,这在儿童身上是看不到的。成人和年龄较大的儿童对OSP进行类转换(IgG和IgA)血清抗体反应,这在仅对OSP有IgM反应的幼儿中没有发现。年轻参与者缺乏类别转换抗体反应和对OSP的记忆B细胞反应可能是由于缺乏先前接触霍乱弧菌,并且可以解释为什么在幼儿接种疫苗后保护作用减弱得更快。
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