Cross-reactive immunogenicity of group A streptococcal vaccines designed using a recurrent neural network to identify conserved M protein linear epitopes.
Cross-reactive immunogenicity of group A streptococcal vaccines designed using a recurrent neural network to identify conserved M protein linear epitopes.
复制标题
DOI：
10.1016/j.vaccine.2021.01.075
复制
发表时间：
2021-03-19
期刊：
影响因子：
5.5
通讯作者：
Baudry J
中科院分区：
文献类型：
--
作者：
Spencer JA;Penfound T;Salehi S;Aranha MP;Wade LE;Agarwal R;Smith JC;Dale JB;Baudry J
A组链球菌（Strep A）的M蛋白是主要的毒力决定因子和保护性抗原。该蛋白的N-末端序列定义了200多种M型链球菌A，并且还包含引发调理素抗体的表位，其中一些与异源M型交叉反应。目前开发广泛保护性的基于M蛋白的疫苗的努力是针对鉴定位于簇相关M蛋白的N-末端区域中的潜在交叉保护性表位以用作疫苗抗原。在这项研究中，我们使用了一种综合的方法，使用递归神经网络ABCpred和IEDB表位保护分析工具来预测来自117种临床相关的M型Strep A（约占全球Strep A感染的88%）的16个残基线性B细胞表位。为了检查这些基于表位的疫苗的免疫原性，将与37种异源M蛋白共有≥60%序列同一性的9种肽掺入两种重组杂合蛋白疫苗中，其中表位分别重复2次或3次。免疫兔的联合免疫应答显示，疫苗引起针对同源N-末端1-50个氨基酸合成M肽中存在的所有9种疫苗表位的显著水平的抗体，以及针对37种异源M肽中预测含有相似表位的16种的交叉反应性抗体。交叉反应性抗体的表位特异性通过ELISA抑制测定来确认，并且在基于HL-60的杀菌测定中测定功能调理素活性。这些结果为将来设计具有广泛保护性的M蛋白A型链球菌疫苗提供了重要信息。
The M protein of group A streptococci (Strep A) is a major virulence determinant and protective antigen. The N-terminal sequence of the protein defines the more than 200 M types of Strep A and also contains epitopes that elicit opsonic antibodies, some of which cross-react with heterologous M types. Current efforts to develop broadly protective M protein-based vaccines are directed at identifying potential cross-protective epitopes located in the N-terminal regions of cluster-related M proteins for use as vaccine antigens. In this study, we have used a comprehensive approach using the recurrent neural network ABCpred and IEDB epitope conservancy analysis tools to predict 16 residue linear B-cell epitopes from 117 clinically relevant M types of Strep A (~88% of global Strep A infections). To examine the immunogenicity of these epitope-based vaccines, nine peptides that together shared ≥60% sequence identity with 37 heterologous M proteins were incorporated into two recombinant hybrid protein vaccines, in which the epitopes were repeated 2 or 3 times, respectively. The combined immune responses of immunized rabbits showed that the vaccines elicited significant levels of antibodies against all nine vaccine epitopes present in homologous N-terminal 1–50 amino acid synthetic M peptides, as well as cross-reactive antibodies against 16 of 37 heterologous M peptides predicted to contain similar epitopes. The epitope-specificity of the cross-reactive antibodies was confirmed by ELISA inhibition assays and functional opsonic activity was assayed in HL-60-based bactericidal assays. The results provide important information for the future design of broadly protective M protein-based Strep A vaccines.
登录
查看更多内容
DOI：
10.1093/cid/cix599
发表时间：
2017-10-16
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Frost HR;Laho D;Sanderson-Smith ML;Licciardi P;Donath S;Curtis N;Kado J;Dale JB;Steer AC;Smeesters PR
通讯作者：
Smeesters PR
影响因子：
15.3
作者：
BEACHEY, EH;SEYER, JM;DALE, JB
通讯作者：
DALE, JB
影响因子：
6.7
作者：
Gustafsson MC;Lannergård J;Nilsson OR;Kristensen BM;Olsen JE;Harris CL;Ufret-Vincenty RL;Stålhammar-Carlemalm M;Lindahl G
通讯作者：
Lindahl G
影响因子：
3
作者：
Bui, Huynh-Hoa;Sidney, John;Li, Wei;Fusseder, Nicolas;Sette, Alessandro
通讯作者：
Sette, Alessandro
影响因子：
4.8
作者：
Salehi, Sanaz;Hohn, Claudia M.;Dale, James B.
通讯作者：
Dale, James B.