Mumps virus neurovirulence assessment-impact of viral doses, animal sex and age on results dispersion

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2024-11-09 DOI:10.1016/j.vaccine.2024.126487

Maja Lang Balija, Maja Jagušić, Dubravko Forčić, Jelena Ivančić-Jelečki, Tanja Košutić Gulija

{"title":"Mumps virus neurovirulence assessment-impact of viral doses, animal sex and age on results dispersion","authors":"Maja Lang Balija, Maja Jagušić, Dubravko Forčić, Jelena Ivančić-Jelečki, Tanja Košutić Gulija","doi":"10.1016/j.vaccine.2024.126487","DOIUrl":null,"url":null,"abstract":"<div><div>Mumps epidemics highlight the necessity for new live mumps vaccines. For vaccine candidate neurosafety assessment, the most commonly used test is the rat-based neurovirulence test (RNVT). Its main experimental and ethical deficiency is the results dispersion which requires large number of animals to obtain statistically relevant results.</div><div>To additionally characterize the RNVT the impact of two experimental animal characteristics, age for inoculation and sex, as well as range of infectious viral doses were analysed. Results obtained from two neurovirulent mumps viruses, SHdeopti-MRV2 and 9218/Zg98, demonstrated no corelation between animal sex and RNVT results (<em>p</em> = 0.9638 and <em>p</em> = 0.3337). Analysis of animal inoculation age found that hydrocephalus formation is impaired in neonatal rats older than 3 days. The inoculation period could be extended from first to the second postanatal day without the impact on RNVT results (<em>p</em> = 0.5865).</div><div>RNVT results demonstrated robustness to infectious doses in a range from 100 to 1000 PFU, but using the non-standard infectious doses,10 PFU or 100 CCID50, poses a risk of underestimating the neurovirulence potential of the MuV. However, none of the analysed parameters influenced the high dispersion of results.</div><div>In conclusion, although our finding will facilitate the implementation of the RNVT, the dispersion of the results indicates the need for a better mumps neurovirulence test that would align more closely with the 3R principles.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"43 ","pages":"Article 126487"},"PeriodicalIF":4.5000,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Vaccine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0264410X24011691","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Mumps epidemics highlight the necessity for new live mumps vaccines. For vaccine candidate neurosafety assessment, the most commonly used test is the rat-based neurovirulence test (RNVT). Its main experimental and ethical deficiency is the results dispersion which requires large number of animals to obtain statistically relevant results.

To additionally characterize the RNVT the impact of two experimental animal characteristics, age for inoculation and sex, as well as range of infectious viral doses were analysed. Results obtained from two neurovirulent mumps viruses, SHdeopti-MRV2 and 9218/Zg98, demonstrated no corelation between animal sex and RNVT results (p = 0.9638 and p = 0.3337). Analysis of animal inoculation age found that hydrocephalus formation is impaired in neonatal rats older than 3 days. The inoculation period could be extended from first to the second postanatal day without the impact on RNVT results (p = 0.5865).

RNVT results demonstrated robustness to infectious doses in a range from 100 to 1000 PFU, but using the non-standard infectious doses,10 PFU or 100 CCID50, poses a risk of underestimating the neurovirulence potential of the MuV. However, none of the analysed parameters influenced the high dispersion of results.

In conclusion, although our finding will facilitate the implementation of the RNVT, the dispersion of the results indicates the need for a better mumps neurovirulence test that would align more closely with the 3R principles.

查看原文本刊更多论文

腮腺炎病毒神经病毒性评估--病毒剂量、动物性别和年龄对结果散布的影响。

流行性腮腺炎疫情凸显了新型流行性腮腺炎活疫苗的必要性。在候选疫苗的神经安全性评估中，最常用的试验是大鼠神经毒力试验（RNVT）。它在实验和伦理方面的主要缺陷是结果分散，需要大量动物才能获得统计相关的结果。为了进一步说明 RNVT 的特点，我们分析了两种实验动物特征（接种年龄和性别）以及传染性病毒剂量范围的影响。两种神经病毒性腮腺炎病毒（SHdeopti-MRV2 和 9218/Zg98）的结果表明，动物性别与 RNVT 结果之间没有核心关系（p = 0.9638 和 p = 0.3337）。对动物接种年龄的分析发现，3 天以上的新生大鼠脑积水的形成会受到影响。接种期可以从出生后第一天延长到第二天，但不会影响 RNVT 结果（p = 0.5865）。RNVT 结果表明，感染剂量在 100 到 1000 PFU 的范围内都是稳健的，但使用非标准感染剂量（10 PFU 或 100 CCID50）有可能低估 MuV 的神经感染潜力。然而，没有一个分析参数会影响结果的高度分散性。总之，尽管我们的发现将有助于 RNVT 的实施，但结果的分散性表明需要一种更好的流行性腮腺炎神经毒力检测方法，使其更符合 3R 原则。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Vaccine 医学-免疫学

CiteScore

8.70

自引率

5.50%

发文量

992

审稿时长

131 days

期刊介绍： Vaccine is unique in publishing the highest quality science across all disciplines relevant to the field of vaccinology - all original article submissions across basic and clinical research, vaccine manufacturing, history, public policy, behavioral science and ethics, social sciences, safety, and many other related areas are welcomed. The submission categories as given in the Guide for Authors indicate where we receive the most papers. Papers outside these major areas are also welcome and authors are encouraged to contact us with specific questions.