Variations in antibody repertoires correlate with vaccine responses.
Variations in antibody repertoires correlate with vaccine responses.
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DOI：
10.1101/gr.276027.121
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发表时间：
2022-04
期刊：
影响因子：
7
通讯作者：
Pevzner PA
中科院分区：
文献类型：
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作者：
Safonova Y;Shin SB;Kramer L;Reecy J;Watson CT;Smith TPL;Pevzner PA
疫苗开发中的一个重要挑战是找出为什么疫苗在一些人身上成功，在另一些人身上失败。尽管抗体谱系掌握着回答这个问题的关键，但到目前为止，旨在揭示免疫球蛋白基因变异如何影响疫苗反应的个性化免疫基因组学研究很少。我们对204头接种了牛呼吸道疾病(BRD)疫苗的小牛进行了一项免疫测序研究，目的是揭示免疫球蛋白基因的变异和影响疫苗应答效果的体细胞超突变。我们的研究是迄今为止在包括人类在内的所有物种中报道的最大的纵向个性化免疫基因组学研究。为了分析生成的数据集，我们开发了一种算法来识别免疫球蛋白基因的变异(以及频繁的体细胞超突变)，这些变异影响抗体库的各种特征和中和抗体的效价。与相对较短的人类抗体相比，牛拥有很大一部分超长抗体，这些抗体开启了新的治疗机会。我们的研究表明，超长抗体是针对北美最昂贵的肉牛疾病的免疫反应的关键组成部分。检测到的牛免疫球蛋白基因变异与BRD疫苗的成败有关，有可能指导正在进行的育种计划中的个体牛的选择。
An important challenge in vaccine development is to figure out why a vaccine succeeds in some individuals and fails in others. Although antibody repertoires hold the key to answering this question, there have been very few personalized immunogenomics studies so far aimed at revealing how variations in immunoglobulin genes affect a vaccine response. We conducted an immunosequencing study of 204 calves vaccinated against bovine respiratory disease (BRD) with the goal to reveal variations in immunoglobulin genes and somatic hypermutations that impact the efficacy of vaccine response. Our study represents the largest longitudinal personalized immunogenomics study reported to date across all species, including humans. To analyze the generated data set, we developed an algorithm for identifying variations of the immunoglobulin genes (as well as frequent somatic hypermutations) that affect various features of the antibody repertoire and titers of neutralizing antibodies. In contrast to relatively short human antibodies, cattle have a large fraction of ultralong antibodies that have opened new therapeutic opportunities. Our study reveals that ultralong antibodies are a key component of the immune response against the costliest disease of beef cattle in North America. The detected variants of the cattle immunoglobulin genes, which are implicated in the success/failure of the BRD vaccine, have the potential to direct the selection of individual cattle for ongoing breeding programs.
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影响因子：
4.3
作者：
Bhardwaj, Vinnu;Franceschetti, Massimo;Safonova, Yana
通讯作者：
Safonova, Yana
影响因子：
9.2
作者：
Lee JH;Toy L;Kos JT;Safonova Y;Schief WR;Havenar-Daughton C;Watson CT;Crotty S
通讯作者：
Crotty S
影响因子：
3.3
作者：
Kramer, L. M.;Mayes, M. S.;Reecy, J. M.
通讯作者：
Reecy, J. M.
DOI：
10.1073/pnas.1417683112
发表时间：
2015-02-24
影响因子：
11.1
作者：
Gadala-Maria, Daniel;Yaari, Gur;Kleinstein, Steven H.
通讯作者：
Kleinstein, Steven H.
个体化 V 基因数据库的产生揭示了高水平的免疫球蛋白遗传多样性。
影响因子：
16.6
作者：
通讯作者：
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