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脂质纳米颗粒配制的犬瘟热DNA疫苗在犬、狐和貉中的安全性和免疫原性

Safety and Immunogenicity of a Canine Distemper DNA Vaccine Formulated with Lipid Nanoparticles in Dogs, Foxes, and Raccoon Dogs.

作者信息

Huo Hong, Wang Han, Liang Shulin, Wang Zilong, Wang Jinming, Wang Qingzhu, Li Chan, Tao Yuting, Ge Jinying, Wen Zhiyuan, Wang Jinliang, Chen Weiye, Wang Xijun, Shuai Lei, Bu Zhigao

机构信息

State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.

Harbin Enwei Biopharmaceutical Co., Ltd., Harbin 150069, China.

出版信息

Vaccines (Basel). 2025 Jun 6;13(6):614. doi: 10.3390/vaccines13060614.

DOI:10.3390/vaccines13060614
PMID:40573945
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12197581/
Abstract

BACKGROUND

canine distemper (CD) is a highly contagious and fatal disease caused by canine distemper virus (CDV), posing a significant threat to carnivores. New CDV strain circulation and multi-species infection may lead to the potential dilemma of safety concern and insufficient efficacy of the commercial modified live vaccines. Safe and effective vaccines for canine and wildlife prevention of CD need to be continuously updated and developed.

METHODS

we developed two DNA vaccines, p17F-LNP and p17H-LNP, encoding the fusion protein (F) or hemagglutinin protein (H) of a field CDV strain (HLJ17) and encapsulated in lipid nanoparticles (LNPs). Serum neutralizing antibody (NAb) was evaluated via neutralization tests, and mouse serum cytokine detection were evaluated via ELISA.

RESULTS

immunization of p17F-LNP and p17H-LNP monovalent or bivalent were safe, and induced robust CDV NAb and cytokine responses in mice. LNP encapsulation improved immune responses compared to naked DNA formulation, and the bivalent formulation of p17F-LNP and p17H-LNP (p17F/H-LNP) exhibited synergistic effects with a high level of immune responses. Moreover, two doses of p17F/H-LNP induced long-lasting CDV NAb for over 300 days in dogs, and prime and boost NAb responses in foxes and raccoon dogs.

CONCLUSIONS

the preliminary findings provided here warrant further development of the p17F/H-LNP vaccine for animal targets against CDV infection.

摘要

背景

犬瘟热(CD)是由犬瘟热病毒(CDV)引起的一种高度传染性和致命性疾病,对食肉动物构成重大威胁。新的CDV毒株传播和多物种感染可能导致商业改良活疫苗安全性担忧和效力不足的潜在困境。需要持续更新和研发用于犬类和野生动物预防CD的安全有效疫苗。

方法

我们开发了两种DNA疫苗,p17F-LNP和p17H-LNP,它们编码一株野外CDV毒株(HLJ17)的融合蛋白(F)或血凝素蛋白(H),并封装在脂质纳米颗粒(LNP)中。通过中和试验评估血清中和抗体(NAb),通过ELISA评估小鼠血清细胞因子检测。

结果

p17F-LNP和p17H-LNP单价或双价免疫是安全的,并在小鼠中诱导了强烈的CDV NAb和细胞因子反应。与裸DNA制剂相比,LNP封装改善了免疫反应,并且p17F-LNP和p17H-LNP的双价制剂(p17F/H-LNP)表现出协同效应,具有高水平的免疫反应。此外,两剂p17F/H-LNP在犬中诱导了超过300天的持久CDV NAb,并在狐狸和貉中引发了初次和加强NAb反应。

结论

此处提供的初步研究结果保证了p17F/H-LNP疫苗针对动物目标预防CDV感染的进一步研发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1260/12197581/bd36ed5bbc11/vaccines-13-00614-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1260/12197581/bd36ed5bbc11/vaccines-13-00614-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1260/12197581/bd36ed5bbc11/vaccines-13-00614-g002.jpg

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