Alam Mohammad Murshid, Leung Daniel T, Akhtar Marjahan, Nazim Mohammad, Akter Sarmin, Uddin Taher, Khanam Farhana, Mahbuba Deena Al, Ahmad Shaikh Meshbahuddin, Bhuiyan Taufiqur Rahman, Calderwood Stephen B, Ryan Edward T, Qadri Firdausi
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
Clin Vaccine Immunol. 2013 Oct;20(10):1541-8. doi: 10.1128/CVI.00341-13. Epub 2013 Aug 7.
Antibody avidity for antigens following disease or vaccination increases with affinity maturation and somatic hypermutation. In this study, we followed children and adults in Bangladesh for 1 year following oral cholera vaccination and measured the avidity of antibodies to the T cell-dependent antigen cholera toxin B subunit (CTB) and the T cell-independent antigen lipopolysaccharide (LPS) in comparison with responses in other immunological measurements. Children produced CTB-specific IgG and IgA antibodies of high avidity following vaccination, which persisted for several months; the magnitudes of responses were comparable to those seen in adult vaccinees. The avidity of LPS-specific IgG and IgA antibodies in vaccinees increased significantly shortly after the second dose of vaccine but waned rapidly to baseline levels thereafter. CTB-specific memory B cells were present for only a short time following vaccination, and we did not find significant memory B cell responses to LPS in any age group. For older children, there was a significant correlation between CTB-specific memory T cell responses after the second dose of vaccine and CTB-specific IgG antibody avidity indices over the subsequent year. These findings suggest that vaccination induces a longer-lasting increase in the avidity of antibodies to a T cell-dependent antigen than is measured by a memory B cell response to that antigen and that early memory T cell responses correlate well with the subsequent development of higher-avidity antibodies.
疾病或疫苗接种后,抗体对抗原的亲和力会随着亲和力成熟和体细胞超突变而增加。在本研究中,我们在孟加拉国对儿童和成人进行了口服霍乱疫苗接种后的为期1年的随访,并测量了针对T细胞依赖性抗原霍乱毒素B亚基(CTB)和T细胞非依赖性抗原脂多糖(LPS)的抗体亲和力,同时与其他免疫测量结果进行比较。接种疫苗后,儿童产生了高亲和力的CTB特异性IgG和IgA抗体,这些抗体持续了数月;反应强度与成年接种者相当。接种者中LPS特异性IgG和IgA抗体的亲和力在第二剂疫苗接种后不久显著增加,但此后迅速降至基线水平。接种疫苗后,CTB特异性记忆B细胞仅存在很短时间,并且我们在任何年龄组中均未发现对LPS的显著记忆B细胞反应。对于年龄较大的儿童,第二剂疫苗接种后的CTB特异性记忆T细胞反应与随后一年中CTB特异性IgG抗体亲和力指数之间存在显著相关性。这些发现表明,与针对该抗原的记忆B细胞反应所测量的相比,疫苗接种诱导了针对T细胞依赖性抗原的抗体亲和力的更持久增加,并且早期记忆T细胞反应与随后更高亲和力抗体的产生密切相关。