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.

中文翻译：

---

抗体库的变化与疫苗反应相关


疫苗开发的一个重要挑战是弄清楚为什么疫苗在某些个体中成功而在另一些个体中失败。尽管抗体库是回答这个问题的关键，但迄今为止，很少有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。我们对 204 头接种牛呼吸道疾病 (BRD) 疫苗的小牛进行了免疫测序研究，目的是揭示影响疫苗反应功效的免疫球蛋白基因变异和体细胞超突变。我们的研究代表了迄今为止针对包括人类在内的所有物种进行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滴度。与相对较短的人类抗体相比，牛拥有很大一部分超长抗体，这开辟了新的治疗机会。我们的研究表明，超长抗体是针对北美肉牛最昂贵的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 疫苗的成功/失败有关，有可能指导正在进行的育种计划中个体牛的选择。