PEDV减毒活疫苗对新生儿保护的安全性和有效性。

IF 6.9 1区 医学 Q1 IMMUNOLOGY
Wentao Li, Basav N Hangalapura, Paul van den Elzen, Erwin van den Born, Frank J M van Kuppeveld, Peter J M Rottier, Berend-Jan Bosch
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引用次数: 0

摘要

猪流行性腹泻病毒(PEDV)在新生仔猪中引起严重腹泻病,死亡率高。为了保护哺乳仔猪,诱导母猪乳原免疫的母方疫苗接种策略至关重要。为了开发改良的活疫苗候选物,我们产生了基因组改变的重组病毒,如缺失ORF3附属基因(ΔORF3),缺失刺突糖蛋白n端唾液酸结合域(SΔN),以及病毒基因组中刺突、包膜、基质和核衣壳基因(SEMN→ESMN)的重排。对这些重组pedv在新生仔猪中的安全性、毒力和免疫原性进行了评价。感染亲本病毒的仔猪表现出严重腹泻和高死亡率。单独删除ORF3不能使病毒减弱。基因顺序的额外重排降低了毒力:rPEDV-ΔORF3-ESMN感染引起中度腹泻,死亡率为50%。SΔN重组病毒,特别是当与其他基因组改变结合时,表现出显著降低的毒力,引起轻度腹泻,无死亡。这些减毒病毒在肠道中保留了复制能力,并诱导了体液免疫反应(IgA和IgG)。rPEDV-SΔN候选疫苗因其良好的安全性和免疫原性而被选中,在妊娠母猪疫苗接种和子代挑战研究中进行了测试,以确定其诱导乳原免疫并赋予子代保护的能力。尽管IgG应答强烈,但接种rPEDV-SΔN的母猪血清IgA水平较低,无法保护仔猪免受PEDV的致命攻击。我们的研究确定了PEDV的关键毒力因子,并说明了开发一种减毒活疫苗的挑战,这种疫苗既要平衡新生仔猪的安全性,又要在母猪中有足够的繁殖能力来刺激乳原保护性免疫。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Safety and efficacy of live attenuated PEDV vaccines for neonatal protection.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrheal disease with high mortality in neonatal piglets. To protect suckling piglets, maternal vaccination strategies that induce lactogenic immunity in sows are crucial. To develop modified live vaccine candidates, we generated recombinant viruses with genome alterations such as deletion of the ORF3 accessory gene (ΔORF3), deletion of the N-terminal sialic acid binding domain of the spike glycoprotein (SΔN), and rearrangement of the spike, envelope, matrix and nucleocapsid genes (SEMN → ESMN) in the viral genome. These recombinant PEDVs were evaluated for their safety, virulence and immunogenicity in neonatal piglets. Piglets infected with the parental virus exhibited severe diarrhea and high mortality. Deletion of ORF3 alone did not attenuate the virus. Additional rearrangement of the gene order reduced virulence: rPEDV-ΔORF3-ESMN infection caused moderate diarrhea with a 50% mortality rate. The SΔN recombinant viruses, particularly when combined with other genome alterations, showed significantly reduced virulence, causing mild diarrhea and no mortality. These attenuated viruses retained their replicative ability in the gut and induced humoral immune responses (IgA and IgG). The rPEDV-SΔN vaccine candidate, selected for its favorable safety and immunogenicity profile, was tested in a pregnant sow vaccination and offspring challenge study for its ability to induce lactogenic immunity and confer protection to the offspring. Despite strong IgG responses, sow vaccination with rPEDV-SΔN resulted in low IgA serum levels and failed to protect piglets from virulent PEDV challenge. Our study defines key virulence factors for PEDV and illustrates the challenge of developing a live-attenuated vaccine that balances safety in neonatal piglets with sufficient replicative capacity in sows to stimulate lactogenic protective immunity.

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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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