猪流行性腹泻疫苗研究进展

doi:10.11843/j.issn.0366-6964.2025.03.007

摘要/Abstract

摘要：

猪流行性腹泻(porcine epidemic diarrhea，PED)是由猪流行性腹泻病毒(porcine epidemic diarrhea virus，PEDV)引起的一种传染性肠道疾病，可造成猪群暴发腹泻和初生仔猪大量死亡。2010年，高致病性的PEDV变异毒株出现并在全球范围内传播，已成为当前猪腹泻病的主要病原之一，对全球养猪业造成巨大损失。疫苗免疫是防控PED的最主要措施。现有PED商品化疫苗以传统灭活疫苗和弱毒疫苗为主。近年来，随着基因工程技术的发展，亚单位疫苗、病毒样颗粒疫苗、重组活载体疫苗、转基因植物疫苗和核酸疫苗等的研究也都取得了突破性进展。由于PEDV变异频繁，不断给疫苗研发带来新的挑战，高效的疫苗研发平台及基因工程疫苗对未来PED防控至关重要。本文对PEDV的病原学特征和最新的疫苗研究进展进行了系统综述，并展望未来的疫苗发展方向，以期为有效防控PED提供参考依据。

关键词: 猪流行性腹泻, 猪流行性腹泻病毒, 灭活疫苗, 弱毒疫苗, 基因工程疫苗, 核酸疫苗

Abstract:

The porcine epidemic diarrhea (PED) is an infectious intestinal disease caused by porcine epidemic diarrhea virus (PEDV), which results in an outbreak of diarrhea in pigs and high mortality in newborn piglet. In 2010, a highly pathogenic mutant strain of PEDV emerged and spread globally, which has presently been one of the main pathogens of porcine diarrhea and caused large losses for the global swine industry. Vaccination is the primary measure for preventing and controlling PED. Currently, available commercial PED vaccines mainly consist of traditional inactivated and attenuated vaccines. With the development of genetic engineering technologies in recent years, significant advancements have been made in the study of subunit vaccines, virus-like particle vaccines, recombinant vector vaccines, transgenic plant vaccines, and nucleic acid vaccines. The frequent variations of PEDV continues to bring new challenges to the vaccine development. Therefore, efficient vaccine development platforms and engineering vaccines are crucial for future prevention and control of PED. This article provides a systematic review of the pathogenic characteristics of PEDV and the latest advancements in vaccine research, as well as prospects for future vaccine development, aiming to provide a reference for effective prevention and control of PED.

Key words: porcine epidemic diarrhea (PED), porcine epidemic diarrhea virus (PEDV), inactivated vaccine, attenuated vaccine, engineering vaccine, nucleic acid vaccines

中图分类号:

邬沛伶, 李依璇, 王浩杰, 李亚菲, 刘绍蒙, 刘青芸, 王湘如. 猪流行性腹泻疫苗研究进展[J]. 畜牧兽医学报, 2025, 56(3): 1042-1058.

WU Peiling, LI Yixuan, WANG Haojie, LI Yafei, LIU Shaomeng, LIU Qingyun, WANG Xiangru. Research Progress of Porcine Epidemic Diarrhea Vaccine for Pigs[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(3): 1042-1058.

图/表 10

表 1

2024年在签批发猪流行性腹泻商品疫苗信息一览表"

毒株 Strain	疫苗类型 Vaccine type	免疫途径 Immune pathway	免疫对象 Immunization target	生产公司 Production company
TGEV华毒株+PEDV CV777株	猪传染性胃肠炎、猪流行性腹泻二联灭活疫苗	后海穴注射	母猪和断奶仔猪	山东海利生物技术股份有限公司
				四川海林格生物制药有限公司
				吉林正业生物制品股份有限公司
				江苏南农高科技股份有限公司
				广东温氏大华农生物科技有限公司
				北京华夏兴洋生物科技有限公司
				普莱柯生物工程股份有限公司
				商丘美兰生物工程有限公司
				山东滨州沃华生物工程有限公司
				哈药集团生物疫苗有限公司
				中牧实业股份有限公司江西生药厂
				成都史纪生物制药有限公司
		后海穴注射或肌肉注射	母猪和断奶仔猪	青岛蔚蓝生物股份有限公司
		后海穴注射或肌肉注射	母猪和公猪	湖南中岸生物药业有限公司
TGEV弱毒华毒株+PEDV CV777株+PoRV NX株	猪传染性胃肠炎、猪流行性腹泻、猪轮状病毒三联弱毒活疫苗	后海穴注射	母猪、新生仔猪和断奶仔猪	山东海利生物技术股份有限公司
				吉林正业生物制品股份有限公司
				哈尔滨维科生物技术有限公司
TGEV WH-1R株+PEDV AJ1102-R株	猪传染性胃肠炎、猪流行性腹泻二联弱毒活疫苗	肌肉注射	母猪、新生仔猪和断奶仔猪	武汉科前生物股份有限公司
	猪传染性胃肠炎、猪流行性腹泻二联灭活疫苗	肌肉注射、口服免疫	母猪、公猪和新生仔猪	国药集团扬州威克生物工程有限公司
		肌肉注射	母猪和新生仔猪	武汉科前生物股份有限公司
			母猪和新生仔猪	安徽东方帝维生物制品股份有限公司
			母猪、公猪和新生仔猪	山东华宏生物工程有限公司
		肌肉注射	母猪和公猪	杭州佑本动物疫苗有限公司
TGEV HB08株+PEDV ZJ08株	猪传染性胃肠炎、猪流行性腹泻二联弱毒活疫苗	肌肉注射	母猪、新生仔猪和断奶仔猪	瑞普(保定)生物药业有限公司
				中牧实业股份有限公司成都药械厂
				金宇保灵生物药品有限公司
		肌肉注射、后海穴注射、口服免疫	母猪和新生仔猪	兆丰华生物科技有限公司
		后海穴注射或肌肉注射	母猪、公猪和新生仔猪	畜科生物工程有限公司
PEDV XJ-DB2株	猪流行性腹泻灭活疫苗	肌肉注射	母猪、新生仔猪和断奶仔猪	天康生物股份有限公司
TGEV SCJY-1株+PEDV SCSZ-1株	猪传染性胃肠炎、猪流行性腹泻二联弱毒活疫苗	肌肉注射、后海穴注射、口服免疫	母猪、公猪、新生仔猪和断奶仔猪	华派生物工程集团有限公司
		肌肉注射、后海穴注射、口服免疫	母猪、新生仔猪和断奶仔猪	重庆澳龙生物制品有限公司
		肌肉注射、口服免疫	母猪、公猪和新生仔猪	吉林特研生物技术有限责任公司
		/	/	成都史纪生物制药有限公司
TGEV SD/L株+PEDV LW/L株	猪传染性胃肠炎、猪流行性腹泻二联弱毒活疫苗	肌肉注射	母猪和断奶仔猪	青岛易邦生物工程有限公司
				洛阳惠中生物技术有限公司
				齐鲁动物保健品有限公司
			母猪和公猪	杭州佑本动物疫苗有限公司
PEDV CHYJ株	猪流行性腹泻灭活疫苗	滴鼻免疫	母猪	四川海林格生物制药有限公司

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毒株Strain	疫苗类型Vaccine type	批件号Approval number	有效期限Valid period
TGEV SHXB株+PEDV ZJ/15株+PDCoV LYG/14株	猪传染性胃肠炎、猪流行性腹泻、猪丁型冠状病毒三联灭活疫苗	2023036	2023/03/02-2025/03/01
PEDV CHO-3G12株	猪流行性腹泻基因工程亚单位疫苗	2023066	2022/05/31-2024/05/30
PEDV J01株+S06株+Z09株+PoRV G4+G9型	猪流行性腹泻、猪轮状病毒二联灭活疫苗	2023084	2022/01/26-2024/01/25
PEDV HB17-R株+PoRV JS01-R株	猪流行性腹泻、猪轮状病毒二联活疫苗	2023064	2020/05/19-2022/05/18
PEDV ZJ/15株	猪流行性腹泻灭活疫苗	2022064	2021/04/14-2023/04/13
PEDV HeN2017株	猪流行性腹泻灭活疫苗	2023019	2021/03/19-2023/03/18
PEDV HB17株+PoRV JS01株	猪流行性腹泻、猪轮状二联灭活疫苗	2022030	2021/03/29-2023/03/28
PDCoV AK-R株+PEDV WN-R株	猪丁型冠状病毒、猪流行性腹泻二联活疫苗	2022003	2019/05/14-2021/05/13
PEDV FJ-2013株灭活疫苗	猪流行性腹泻灭活疫苗	2020018	2018/03/05-2019/03/04
PEDV TBJS株Ⅱ型活疫苗	猪流行性腹泻Ⅱ型活疫苗	2021004	2018/01/23-2019/01/22
TGEV SD14株+PEDV HuN16株+PDCoV HeN17株	猪传染性胃肠炎、猪流行性腹泻、猪丁型冠状病毒三联灭活疫苗	2021002	2017/08/28-2018/08/27
TGEV WH-1株+PEDV AJ1102株+PDCoV CHN-HN-2014株	猪传染性胃肠炎、猪流行性腹泻、猪丁型冠状病毒三联灭活疫苗	2021003	2016/12/30-2017/12/29
PDCoV SDclone10株+PEDV KB-4clone13株	猪丁型冠状病毒、猪流行性腹泻二联灭活疫苗	2019016	2017/08/28-2018/08/27
TGEV CT130株+PEDV HX115株	猪传染性胃肠炎、猪流行性腹泻二联活疫苗	2018019	2016/12/30-2017/12/29
PEDV KB-4clone13株	猪流行性腹泻灭活疫苗	2018005	2016/09/29-2017/09/28

毒株 Strain	疫苗佐剂 Vaccine adjuvant	免疫对象 Immune target	参考文献 Reference
GF10	氢氧化铝	妊娠母猪	[22]
GS	ISA 61VG和ISA 206	妊娠母猪	[23]
CO2013	/	3周龄仔猪	[24]
rAJ1102-S2′JS2008	/	4周龄仔猪	[25]
AH2012/12	Flic和ISA 201	妊娠母猪	[26]
PT-5	CCL27、CCL28、CCL25和弗氏佐剂	5周龄仔猪	[27]
SGP-M1	Carbopol^® 940 NF聚合物	妊娠母猪	[28]
ZJ08	/	5日龄仔猪	[29]

毒株 Strain	致弱手段 Attenuated measures	免疫剂量 Immune dose	免疫对象 Immune target	参考文献 Reference
S DEL5/ORF3	Vero细胞中连续传代100次	10^6.5 TCID ₅₀·mL^-1	妊娠母猪	[30]
IL20697	Vero细胞中连续传代	10^4.0 TCID₅₀·mL^-1	妊娠母猪	[31]
Aram-P29-CA	Vero细胞中较低温度(32 ℃)下连续传代28次	10^3.0 TCID₅₀·mL^-1	妊娠母猪	[32]
CKT-7 N、CKT-7 T15、CKT-7 T15N、CKT-7 NF、CKT-7 F	在培养基中单独或混合添加(TPCK处理的胰蛋白酶、1% FBS或Na-GCDCA)的Vero细胞中连续传代180次	10^7.0 TCID₅₀·mL^-1	5日龄仔猪	[33]
KDKE4A-SYA	抑制nsp16的2′-O甲基转移酶的活性并敲除S蛋白胞内域的内吞信号序列	/	妊娠母猪	[34]
icPEDV-mute4	抑制nsp1、nsp15和nsp16蛋白的活性	/	4~7日龄仔猪	[35]
r12-N514G、r12-N556G和r12-N514+556G	用天冬酰胺氨基酸替换aa514和aa556位点的丝氨酸	10^4.5 TCID ₅₀·mL^-1	5日龄仔猪	[36]

毒株 Strain	表达系统 Expression system	表达蛋白 Expressed proteins	免疫对象 Immune target	参考文献 Reference
CH/PDS/2015	pET-32a原核表达系统	COE结构域	3月龄仔猪	[37]
CV777	pG5-S1D原核表达系统	aP2蛋白	妊娠母猪	[38]
KM242131	HEK-293T表达系统	S1亚基	断奶仔猪	[39]
AH2012/12	HEK-293T表达系统	S蛋白、S1亚基和S蛋白多表位串联的三聚体蛋白	3日龄仔猪	[40]
CT	昆虫杆状病毒表达系统	S/亚基	妊娠母猪	[41]
PT	家蚕核型多角体病毒	S蛋白	4周龄仔猪	[42]
COJS01	Bac-to-Bac杆状病毒表达系统	S蛋白	新生仔猪	[43]
CT	昆虫杆状病毒表达系统	S蛋白	30日龄仔猪	[44]

毒株 Strain	疫苗载体 Vaccine vector	表达蛋白 Expressed proteins	免疫对象 Immune target	参考文献 Reference
/	乙肝病毒核心衣壳蛋白(HBcAg)	⁷⁴⁸YSNIGVCK⁷⁵⁵	妊娠母猪	[45]
PT	P-BEVS	S、M和E蛋白	4周龄仔猪	[46]
AJ1102	ADDomer	SS2、2C10结构域和A、D位点	断奶仔猪	[48]
GS2022	Trimer-Tag	S1亚基、COE和RBD结构域	妊娠母猪	[49]