Protection Efficacy of Monoclonal Antibodies Targeting Different Regions of Specific SzM Protein from Swine-Isolated Streptococcus equi ssp. zooepidemicus Strains.
Protection Efficacy of Monoclonal Antibodies Targeting Different Regions of Specific SzM Protein from Swine-Isolated Streptococcus equi ssp. zooepidemicus Strains.
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DOI：
10.1128/spectrum.01742-22
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发表时间：
2022-12-21
影响因子：
3.7
通讯作者：
Ma Z
中科院分区：
文献类型：
--
作者：
Song H;Yuan C;Zhang Y;Pan F;Fan H;Ma Z
马链球菌动物寄生虫（Zoopellicus，SEZ）具有广泛的宿主谱，包括人类和家畜。经济特区引起的猪链球菌病已在多个国家暴发流行，猪源分离株通常具有特异性链球菌。类M（szm）基因型。在这项研究中，我们发现，这种特定的szm基因（SzM蛋白）的生产是一个有效的疫苗候选人。与传统疫苗株ST 171相比，该疫苗株在7 d间隔免疫时能提供更好的免疫保护，并能使ΔsezV株对猪分离的SEZ强毒感染产生弱毒。根据这一结果，我们开发了单克隆抗体（单克隆抗体），分别针对该SzM蛋白的可变区和保守区。这些McAb均属于IgG1同种型，具有κ型轻链，具有调理吞噬活性，而不具有凝集或补体激活功能。用3种不同的被动免疫治疗方案评价单克隆抗体的保护效率。抗保守区单克隆抗体能有效地对抗猪分离的SEZ感染，而不需要繁琐的免疫治疗程序。它也部分地防止其他SEZ菌株的感染。与此相反，抗可变区单克隆抗体仅适用于保护宿主免受从猪分离的特定szm型SEZ菌株的侵害，但它对于不同的免疫治疗方案是灵活的。这些数据提供了进一步的信息，以指导衍生的，基因工程的单克隆抗体，有潜在的应用在保护宿主免受猪分离的，高毒力的SEZ感染在未来的发展。重要性猪隔离经济特区以其特有的szm基因序列，对中国和北美的养猪业造成了冲击，并造成了严重的经济损失。尽管SEZ的SzM蛋白已被证明是预防感染的有效疫苗，但大多数先前的研究集中在马分离的菌株上，与猪分离的菌株相比，马分离的菌株具有不同的szm基因类型。在本研究中，我们开发了针对猪分离的SzM蛋白的保守区和可变区的单克隆抗体，并评估其保护效率。本研究为进一步开发嵌合单克隆抗体或其他基因工程单克隆抗体提供了依据。
Streptococcus equi subsp. zooepidemicus (SEZ) has a wide host spectrum, including humans and domestic animals. The SEZ-caused swine streptococcicosis outbreak has occurred in several countries, and the swine-isolated strains usually have specific S. zooepidemicus M-like (szm) gene types. In this study, we found that the production of this specific szm gene (SzM protein) was an effective vaccine candidate. It could provide better protection with a 7-day interval immune procedure than the traditional vaccine strain ST171 and attenuate the strain ΔsezV against swine-isolated hypervirulent SEZ infections. According to this outcome, we developed monoclonal antibodies (McAbs) targeting the variable and conserved regions of this SzM protein, respectively. These McAbs all belong to the IgG1 isotype with a κ type light chain and have opsonophagocytic activity rather than agglutination or complement activation functions. We estimated the protection efficiency of the McAbs with 3 different passive immunotherapy programs. The anti-conserved region McAb can provide effective protection against swine-isolated SEZ infections with only the inconvenient immunotherapy program. It also partially works in preventing infection by other SEZ strains. In contrast, the anti-variable region McAb is only adapted to protect the host against a specific szm type SEZ strain isolated from pigs, but it is flexible for different immunotherapy programs. These data provide further information to guide the development of derived, genetically engineered McAbs that have potential applications in protecting hosts against swine-isolated, hypervirulent SEZ infections in the future. IMPORTANCE The swine-isolated SEZ, with its specific szm gene sequence, has impacted the pig feeding industry in China and North America and has led to serious economic loss. Though the SzM protein of SEZ has been proven to be an effective vaccine in preventing infection, most previous studies focused on horse-isolated strains, which have different szm gene types compared to swine-isolated strains. In this study, we developed the McAbs targeting the conserved and variable regions of this SzM protein from the swine-isolated hypervirulent strains and evaluated their protection efficiency. Our research provided information for the development of chimeric McAbs or other genetically engineered McAbs that have potential applications in protecting pigs against hypervirulent SEZ infections in the future.
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影响因子：
11.8
作者：
Gruszynski K;Young A;Levine SJ;Garvin JP;Brown S;Turner L;Fritzinger A;Gertz RE Jr;Murphy JM;Vogt M;Beall B
通讯作者：
Beall B
影响因子：
3.7
作者：
Aribam SD;Harada T;Elsheimer-Matulova M;Iwata T;Kanehira K;Hikono H;Matsui H;Ogawa Y;Shimoji Y;Eguchi M
通讯作者：
Eguchi M
影响因子：
3.2
作者：
Xiao N;Li J;Li M;Hu Y;Lin H;Fan H
通讯作者：
Fan H
影响因子：
4.9
作者：
Horn, Michael P.;Zuercher, Adrian W.;Lang, Alois B.
通讯作者：
Lang, Alois B.
影响因子：
3.3
作者：
Hau, Samantha J.;Lantz, Kristina;Brockmeier, Susan L.
通讯作者：
Brockmeier, Susan L.