Efficacy test of a Mycoplasma hyorhinis mRNA-LNP vaccine candidate

IF 2.2 Q3 IMMUNOLOGY
Eszter Zsófia Nagy , Levente Szeredi , Hiromi Muramatsu , Noémi Nagy , Dénes Grózner , Zsuzsa Kreizinger , Kinga M. Sulyok , Bandana Pangabam , Lilla Tóth , Rachel H.J. Jun , Dorottya Földi , Enikő Wehmann , Miklós Tenk , Norbert Pardi , Miklós Gyuranecz
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引用次数: 0

Abstract

Background

Mycoplasma (M.) hyorhinis is a widespread bacterium that frequently causes polyserositis and arthritis in post-weaning pigs. Currently, prevention and treatment strategies rely on mitigating risk factors and administering antibiotics, as no vaccines are commercially available in Europe. Developing a safe and efficacious vaccine could provide a long-term solution, reducing the economic impact of M. hyorhinis infections. Therefore, the present study aimed to develop a M. hyorhinis mRNA-LNP vaccine candidate.

Materials and methods

The selected antigens were highly conserved proteins involved in bacterial adhesion. The mRNAs encoding these proteins were produced using established protocols and subsequently encapsulated in lipid nanoparticles through a self-assembly technique. For the in vivo efficacy assessment, three-week-old piglets were immunized with the candidate vaccine, and the injection site was monitored daily. At six weeks of age, the animals were challenged intravenously on two consecutive days. The clinical examinations were performed daily, while blood samples were collected weekly for a M. hyorhinis-specific antibody ELISA and Porcine Interferon gamma (Porcine IFN-γ) ELISA. Three weeks post-challenge, the animals were euthanized for gross and histopathological examinations. Additionally, body temperatures were recorded daily, and the body weights of the animals were measured upon arrival and then at six and nine weeks of age.

Results

After the challenge, the vaccinated group showed significantly higher IgG antibody titers than the positive control. Similarly, the vaccinated group's average daily weight gain was higher than the one of the challenge group. However, the vaccine candidate failed to confer sufficient protection against the clinical signs, pathological and histopathological lesions.

Discussion

Overall, a single dose of mRNA-LNP vaccine candidate was ineffective in preventing the disease caused by M. hyorhinis. Future research should focus on optimizing the vaccine formulation by incorporating additional antigens or adjuvants, implementing a two-dose immunization, or exploring alternative routes of administration.
一种缩支原体mRNA-LNP候选疫苗的效力试验
支原体(m.h orhinis)是一种广泛存在的细菌,经常引起断奶后猪的多浆液炎和关节炎。目前,预防和治疗战略依赖于减轻风险因素和使用抗生素,因为欧洲没有商业化的疫苗。开发一种安全有效的疫苗可以提供一种长期的解决方案,减少喉支原体感染的经济影响。因此,本研究旨在开发一种猪分枝杆菌mRNA-LNP候选疫苗。材料与方法所选抗原为与细菌黏附有关的高度保守蛋白。编码这些蛋白质的mrna使用既定的方案产生,随后通过自组装技术封装在脂质纳米颗粒中。为评估体内有效性,对3周龄仔猪进行候选疫苗免疫,并每天监测注射部位。在六周龄时,连续两天对这些动物进行静脉注射。每天进行临床检查,每周采集血样进行猪嗜血杆菌特异性抗体ELISA和猪干扰素γ(猪IFN-γ) ELISA检测。三周后,对动物实施安乐死,进行大体和组织病理学检查。此外,每天记录体温,并在动物到达后以及6周龄和9周龄时测量体重。结果攻毒后,免疫组IgG抗体滴度明显高于阳性对照组。同样,接种疫苗组的平均每日体重增加高于挑战组。然而,该候选疫苗未能对临床症状、病理和组织病理学病变提供足够的保护。综上所述,单剂量mRNA-LNP候选疫苗在预防猪支原体引起的疾病方面是无效的。未来的研究应侧重于通过加入额外的抗原或佐剂、实施两剂免疫或探索其他给药途径来优化疫苗配方。
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
Vaccine: X
Vaccine: X Multiple-
CiteScore
2.80
自引率
2.60%
发文量
102
审稿时长
13 weeks
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