Serotype independent protection induced by a vaccine based on the IgM protease of Streptococcus suis and proposal for a new immunity-based classification system.

IF 3 2区 农林科学 Q1 VETERINARY SCIENCES
A A C Jacobs, A W F Grommen, S Badbanchi, A J van Hout, T J van Kasteren-Westerneng, L Garcia Morales, R Bron, R P A M Segers
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引用次数: 0

Abstract

The IgM protease (IdeSsuis gene; Gene ID 8153996) of Streptococcus suis is a putative virulence factor that has been shown to be a protective vaccine antigen for pigs (Seele et al. Vaccine 33:2207-12, 2015). To assess its potential as a cross-protective antigen, the amino acid variability among prevalent clinical isolates in various regions and among various serotypes was investigated. Multi-sequence alignment of full-length amino acid sequences of S. suis IgM protease, available in the public domain (status Jan-2022) supplemented with in-house sequences, i.e. a total of 1999 sequences, revealed that the IgM protease of S. suis clusters into three main evolutionary distinct branches: groups A, B and C. Group A, 82% of the sequences in the database, was associated with clinical isolates of various serotypes. Group B, 6% of the strains in the database, was associated with clinical isolates mainly in the EU and mainly belonging to serotype (st) 9. Group C, 12% of the strains in the database, was largely associated with healthy carrier isolates, i.e. nose or tonsil isolates of various serotypes but in particular with st9 and un-typable strains. Within the groups A, B and C, high levels of amino acid identity were observed (> 75%), whereas between groups A and B, the percentage amino acid identity was approximately 30% and between groups A and C approximately 55%. Experimental Escherichia coli expressed recombinant subunit vaccines based on the IgM protease group A sequence of st1 strain B10-99, st2 strain 10 or st7 strain 14009-1, induced serotype independent protection in pigs against challenge with all group A strains tested, i.e. strains of different parts of the phylogenetic tree and of different serotypes including st1, 2, 9 and 14. Protection was observed after vaccination of piglets at 3 and 5 weeks of age and subsequent challenge at 7 weeks but also after vaccination of gilts at 6 and 2 weeks before anticipated parturition and challenge of the offspring up to at least 8 weeks of age. No protection was observed against challenge with st9 strain SZ2000-6264 having group B IgM protease. A recombinant subunit vaccine based on the group B IgM protease sequence, also did not protect against challenge with the homologous group B st9 challenge strain. The results indicate that a vaccine based on a group A IgM protease induces protection against all S. suis strains that express the group A IgM protease. Depending on the geographical region such a vaccine is expected to protect against 60-100% of the virulent S. suis strains. Since the novel proposed IgM protease classification is highly relevant, a PCR was developed and validated, to be able to classify clinical isolates into IgM protease groups A, B and C and predict the cross-protection that can be expected from a group A based IgM protease vaccine.

基于猪链球菌 IgM 蛋白酶的疫苗诱导的独立血清型保护,以及基于免疫的新分类系统建议。
猪链球菌的 IgM 蛋白酶(IdeSsuis 基因;基因编号 8153996)是一种推定的毒力因子,已被证明是猪的保护性疫苗抗原(Seele et al. Vaccine 33:2207-12, 2015)。为评估其作为交叉保护性抗原的潜力,研究人员对不同地区和不同血清型的流行临床分离株之间的氨基酸变异性进行了调查。对可在公共领域(2022 年 1 月)获得的猪链球菌 IgM 蛋白酶全长氨基酸序列进行多序列比对,并补充内部序列,即总共 1999 个序列,发现猪链球菌的 IgM 蛋白酶分为三个主要的进化分支:A 组、B 组和 C 组。B 组,占数据库中菌株的 6%,主要与欧盟的临床分离株有关,主要属于血清型(st)9。C 组(占数据库中菌株的 12%)主要与健康携带者分离株有关,即各种血清型的鼻腔或扁桃体分离株,尤其是血清 9 型和无法分型的菌株。在 A 组、B 组和 C 组中,氨基酸的同一性很高(> 75%),而在 A 组和 B 组之间,氨基酸的同一性约为 30%,在 A 组和 C 组之间,氨基酸的同一性约为 55%。基于 st1 菌株 B10-99、st2 菌株 10 或 st7 菌株 14009-1 的 IgM 蛋白酶 A 组序列的实验性大肠杆菌表达重组亚单位疫苗,可在猪只接种所有测试的 A 组菌株(即系统发生树不同部分的菌株和不同血清型的菌株,包括 st1、2、9 和 14)后诱导出独立于血清型的保护力。在仔猪 3 周龄和 5 周龄接种疫苗并在 7 周龄时进行挑战后,以及在后备母猪预产期前 6 周龄和 2 周龄接种疫苗并在后代至少 8 周龄时进行挑战后,均可观察到保护作用。在接种具有 B 群 IgM 蛋白酶的 st9 株 SZ2000-6264 后,未观察到任何保护作用。基于 B 群 IgM 蛋白酶序列的重组亚单位疫苗也不能抵御同源 B 群 st9 株的挑战。结果表明,以 A 组 IgM 蛋白酶为基础的疫苗可对所有表达 A 组 IgM 蛋白酶的鼠疫菌株产生保护作用。根据不同的地理区域,这种疫苗预计可抵御 60-100% 的猪链球菌毒株。由于新提出的 IgM 蛋白酶分类具有高度相关性,因此开发并验证了一种 PCR,以便能够将临床分离株分为 IgM 蛋白酶 A、B 和 C 组,并预测基于 A 组 IgM 蛋白酶疫苗的交叉保护效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Porcine Health Management
Porcine Health Management Veterinary-Food Animals
CiteScore
5.40
自引率
5.90%
发文量
49
审稿时长
14 weeks
期刊介绍: Porcine Health Management (PHM) is an open access peer-reviewed journal that aims to publish relevant, novel and revised information regarding all aspects of swine health medicine and production.
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