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基于TbpB的口腔黏膜疫苗对由副猪嗜血杆菌西班牙田间分离株不同血清型引起的格拉泽氏病提供异源保护。

TbpB-based oral mucosal vaccine provides heterologous protection against Glässer's disease caused by different serovars of Spanish field isolates of Glaesserella parasuis.

作者信息

González-Fernández Alba, Mencía-Ares Oscar, García-Iglesias María José, Petrocchi-Rilo Máximo, Miguélez-Pérez Rubén, Perelló-Jiménez Alberto, Herencia-Lagunar Elena, Acebes-Fernández Vanessa, Gutiérrez-Martín César B, Martínez-Martínez Sonia

机构信息

Department of Animal Health, Faculty of Veterinary, Universidad de León, León, Spain.

IREC (UCLM and CSIC), SaBio, Hunting Resources Research Institute, Ciudad Real, Spain.

出版信息

Porcine Health Manag. 2024 Nov 28;10(1):57. doi: 10.1186/s40813-024-00404-7.

Abstract

BACKGROUND

Glaesserella parasuis (G. parasuis) is the primary agent of Glässer's disease, significantly affecting nursery and early fattening piglets. Current prophylactic measures, mainly serovar-specific bacterins administered to sows, are limited by maternal immunity, which can interfere with active immunization in piglets. Subunit vaccines containing G. parasuis-specific antigenic molecules show promise but are not yet commercially available. Transferrin-binding proteins (Tbp), which enable G. parasuis to acquire iron in low-iron environments like mucosal surfaces, have been proposed as potential vaccine antigens. The mucosal administration of a TbpB-based subunit vaccine could provide a promising solution to overcome the limitations posed by maternal immunity, offering an effective approach to control the disease in weaning piglets. This study, conducted in two phases, primarily evaluates (days 0-45) the immunogenicity of a two-dose oral mucosal TbpB-based subunit vaccine (TbpB) administered to colostrum-deprived piglets, and subsequently (days 45-52), its heterologous protection by challenging these piglets with four G. parasuis clinical isolates from different TbpB clusters (I, III) and serovars (SV1, SV4, SV5, SV7) recovered from Spanish pig farms.

RESULTS

The oral mucosal administration of the two-dose TbpB-based vaccine induced a robust humoral immune response in immunized colostrum-deprived piglets, significantly increasing IgA and IgM concentration 15 days after the second dose (p < 0.01). Upon challenge with four G. parasuis clinical isolates, the vaccine demonstrated heterologous protection, markedly improving survival rates (OR: 8.45; CI 95%: 4.97-14.36) and significantly reducing clinical signs and lesions, regardless of the TbpB cluster and serovar. The vaccine reduced G. parasuis colonization in the respiratory tract (p < 0.0001) and G. parasuis systemic target tissues, like tarsus and carpus joints, liver, and brain (p < 0.05). Immunohistochemical analysis showed a lower macrophage count in different lung locations of immunized piglets (p < 0.0001).

CONCLUSIONS

This study demonstrates that oral mucosal administration of the TbpB subunit vaccine in piglets provides effective heterologous protection against diverse virulent European G. parasuis field isolates, significantly reducing bacterial colonization and dissemination. This vaccine offers a promising alternative to traditional bacterins, overcoming limitations due to maternal immunity, and represents a strong candidate for universal vaccination against Glässer's disease.

摘要

背景

副猪嗜血杆菌(G. parasuis)是格拉泽氏病的主要病原体,对保育猪和早期育肥仔猪有显著影响。目前的预防措施主要是给母猪接种血清型特异性菌苗,但受母源免疫力的限制,母源免疫力会干扰仔猪的主动免疫。含有G. parasuis特异性抗原分子的亚单位疫苗显示出前景,但尚未商业化。转铁蛋白结合蛋白(Tbp)能使G. parasuis在粘膜表面等低铁环境中获取铁,已被提议作为潜在的疫苗抗原。基于TbpB的亚单位疫苗经粘膜给药可能是克服母源免疫力限制的一个有前景的解决方案,为控制断奶仔猪的疾病提供了一种有效方法。本研究分两个阶段进行,主要评估(第0 - 45天)给初乳剥夺仔猪口服两剂基于TbpB的亚单位疫苗(TbpB)的免疫原性,随后(第45 - 52天),通过用从西班牙猪场分离的来自不同TbpB簇(I、III)和血清型(SV1、SV4、SV5、SV7)的4株G. parasuis临床分离株对这些仔猪进行攻毒来评估其异源保护作用。

结果

给初乳剥夺仔猪口服两剂基于TbpB的疫苗诱导了强烈的体液免疫反应,在第二剂后15天显著增加了IgA和IgM浓度(p < 0.01)。在用4株G. parasuis临床分离株攻毒后,该疫苗显示出异源保护作用,显著提高了存活率(OR:8.45;95%CI:4.97 - 14.36),并显著减轻了临床症状和病变,无论TbpB簇和血清型如何。该疫苗减少了呼吸道中G. parasuis的定植(p < 0.0001)以及G. parasuis在全身靶组织如跗关节和腕关节以及肝脏和大脑中的定植(p < 0.05)。免疫组织化学分析显示免疫仔猪不同肺部位的巨噬细胞计数较低(p < 0.0001)。

结论

本研究表明,给仔猪口服粘膜TbpB亚单位疫苗可提供有效的异源保护,抵御多种欧洲强毒G. parasuis田间分离株,显著减少细菌定植和传播。该疫苗为传统菌苗提供了一种有前景的替代方案,克服了母源免疫力的限制,是针对格拉泽氏病进行通用疫苗接种的有力候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31df/11606180/b25e226a85dc/40813_2024_404_Fig1_HTML.jpg

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