猪流行性腹泻疫苗研究进展

doi:10.16431/j.cnki.1671-7236.2024.11.035

摘要/Abstract

摘要： 近年来，随着中国养猪事业的高速发展，猪流行性腹泻(PED)已成为猪群的重要传染病，PED是由猪流行性腹泻病毒(PEDV)引起的,以腹泻、呕吐、脱水为特征的急性病毒性传染病。PED主要通过呼吸道和消化道传播，哺乳仔猪最易感，死亡率可高达100%，给养猪业造成了巨大的经济损失。PEDV是单股正链RNA病毒，具有4个主要结构蛋白、16个非结构蛋白和1个辅助蛋白ORF3。自2010年以来，该病毒变异株传播范围不断扩大，流行趋势日益复杂，经典毒株(CV777)相关疫苗已无法提供有效保护。因此，开发更加安全、有效的疫苗已迫在眉睫。灭活疫苗安全性高，但需多次接种且保护效果不佳；弱毒疫苗免疫原性良好，但存在毒力返祖风险；亚单位疫苗不携带病毒其他蛋白结构，使用安全、价格便宜，但其免疫原性差；重组病毒活载体疫苗可诱导产生特异性免疫反应，但安全性不足；重组细菌活载体疫苗能口服刺激机体黏膜免疫，并且载体具有佐剂作用，但其免疫效率不高；转基因植物疫苗安全稳定，但表达量低且研发周期长；核酸疫苗研发周期短、灵活性高，但安全性不高、外源基因易与宿主基因重组。随着相关研究的深入，各类疫苗研究已取得重要研究成果。笔者就PED灭活疫苗、弱毒疫苗、亚单位疫苗、重组病毒活载体疫苗、重组细菌活载体疫苗、转基因植物疫苗、核酸疫苗进行综述，以期为PED的防治和新型疫苗研发提供参考。

关键词: 猪流行性腹泻; 猪流行性腹泻病毒(PEDV); 流行特点; 疫苗

Abstract: In recent years,with the rapid development of pig industry in China,porcine epidemic diarrhea (PED) has become an important infectious disease in pigs.PED is an acute viral infectious disease caused by Porcine epidemic diarrhea virus (PEDV),characterized by diarrhea and dehydration.PED is mainly transmitted through the respiratory and digestive tracts,and lactating piglets are most susceptible to it,and the mortality rate can be as high as 100%,which has caused great economic losses to the pig industry.PEDV is a single-stranded positive-sense RNA virus,it has 4 major structural proteins,16 non-structural proteins,and 1 auxiliary protein ORF3.Since 2010,the spread of the mutated strain of the virus has been expanding and the epidemiological trends have become increasingly complex,the classical strain (CV777)-related vaccines have been unable to provide effective protection.Therefore,it is urgent to develop a safer and more effective vaccine.Inactivated vaccines are safe,but require multiple vaccinations and are not as protective.Attenuated vaccine have good immunogenicity,but there is a risk of virulence regression.Subunit vaccines do not carry other protein structures of the virus and are safe and inexpensive to use,but they are poorly immunogenic.Live virus vector vaccines induce specific immune responses but have an inadequate safety profile.Live bacterial vector vaccines are able to stimulate mucosal immunity in the body by oral administration and the vectors are adjuvant,but their immunization efficiency is not high.Transgenic plant vaccines are safe and stable,but have low expression and long development cycles.Nucleic acid vaccine has a short development cycle and high flexibility,but the safety is not high,and the foreign gene is easy to recombine with the host gene.With the deepening of related research,various types of vaccine research have achieved important research results.This article provided an overview of PED inactivated vaccines,attenuated vaccine,subunit vaccine,live virus vector vaccine,live bacterial vector vaccine,transgenic plant vaccine,and nucleic acid vaccine,in order to provide reference for the prevention and treatment of PED and the development of new vaccines.

Key words: porcine epidemic diarrhea; Porcine epidemic diarrhea virus (PEDV); epidemiological characteristic; vaccine

中图分类号:

S852.4

张洋, 欧云文, 马春霞, 任绍科, 潘琴, 邓书明, 翟佳佳, 杨山山. 猪流行性腹泻疫苗研究进展[J]. 中国畜牧兽医, 2024, 51(11): 5004-5013.

ZHANG Yang, OU Yunwen, MA Chunxia, REN Shaoke, PAN Qin, DENG Shuming, ZHAI Jiajia, YANG Shanshan. Research Progress on Porcine Epidemic Diarrhea Vaccine[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(11): 5004-5013.

参考文献

[1] ZHANG H L，HAN F F，YAN X G，et al.Prevalence and phylogenetic analysis of spike gene of Porcine epidemic diarrhea virus in Henan province，China in 2015-2019[J].Infection，Genetics and Evolution，2021，88：104709.
[2] XU X，LI P F，ZHANG Y T，et al.Comprehensive analysis of synonymous codon usage patterns in orf3 gene of Porcine epidemic diarrhea virus in China[J].Research in Veterinary Science，2019，127(C)：42-46.
[3] ZHANG F F，LUO S X，GU J，et al.Prevalence and phylogenetic analysis of porcine diarrhea associated viruses in Southern China from 2012 to 2018[J]. BMC Veterinary Research，2019，15(1)：470.
[4] 潘红丽，马青兰，苏胖.规模化母猪场流行性腹泻综合防控[J].现代畜牧科技，2023，9：114-118.
PAN H L，MA Q L，SU P.Comprehensive prevention and control of epidemic diarrhea in large-scale sow farms[J].Modern Animal Husbandry Science & Technology，2023,9：114-118.(in Chinese)
[5] LEE C.Porcine epidemic diarrhea virus:An emerging and re-emerging epizootic swine virus[J].Virology Journal，2015，12：193.
[6] 熊谋康，梁太润，刘献辉，等.2020－2021年我国部分地区猪流行性腹泻病毒S1、M和ORF3基因遗传进化分析[J].黑龙江畜牧兽医，2023，15：8-17.
XIONG M K，LIANG T R，LIU X H，et al.Genetic evolution analysis of Porcine epidemic diarrhea virus S1,M and ORF3 genes in some areas of China from 2020 to 2021[J].Heilongjiang Animal Science and Veterinary Medicine，2023，15：8-17.(in Chinese)
[7] SUN Y G，LI R，XIE S，et al.Identification of a novel linear B-cell epitope within the collagenase equivalent domain of Porcine epidemic diarrhea virus spike glycoprotein[J].Virus Research，2019，266：34-42.
[8] WANG R Y，YU R S，CHEN B Q，et al.Identification of host cell proteins that interact with the M protein of Porcine epidemic diarrhea virus[J].Veterinary Microbiology，2020，246：108729.
[9] ZHENG L，WANG X H，GUO D X，et al.Porcine epidemic diarrhea virus E protein suppresses RIG-Ⅰ signaling-mediated interferon-β production[J].Veterinary Microbiology，2021，254：108994.
[10] XU X G，ZHANG H L，ZHANG Q，et al.Porcine epidemic diarrhea virus N protein prolongs S-phase cell cycle,induces endoplasmic reticulum stress,and up-regulates interleukin-8 expression[J].Veterinary Microbiology，2013，164(3-4)：212-221.
[11] 郑亮，郭德轩，于雯,等.猪流行性腹泻病毒蛋白功能研究进展[J].生命的化学，2021，41(6)：1133-1138.
ZHENG L，GUO D X，YU W，et al.Research progress of protein functions of Porcine epidemic diarrhea virus[J].Chemistry of Life,2021,41(6)：1133-1138.(in Chinese)
[12] LI W T，LI H，LIU Y B，et al.New variants of Porcine epidemic diarrhea virus,China,2011[J].Emerging Infectious Diseases，2012，18(8)：1350-1353.
[13] 秦谷雨，杨勇，李郁，等.安徽省仔猪腹泻5种病毒感染情况的调查研究[J].动物医学进展，2012，33(12)：59-63.
QIN G Y,YANG Y,LI Y，et al.Investigation on infection status of five kinds of viruses causing pig diarrhea in Anhui province[J].Progress in Veterinary Medicine,2012，33(12)：59-63.(in Chinese)
[14] 甘海霞，梁晟，韦显凯，等.2011年广西猪群猪流行性腹泻和猪传染性胃肠炎调查[J].动物医学进展，2012，33(10)：125-127.
GAN H X,LIANG S,WEI X K，et al.Investigation on porcine epidemic diarrhea and porcine transmissible gastroenteritis in Guangxi 2011[J].Progress in Veterinary Medicine,2012,33(10)：125-127.(in Chinese)
[15] FAN B C，JIAO D，ZHANG R X，et al.Origin and epidemic status of Porcine epidemic diarrhea virus variants in China[J].Transboundary and Emerging Diseases，2020，67(3)：1364-1370.
[16] 施标，董世娟，朱于敏，等.中国猪流行性腹泻病毒分子流行病学研究进展[J].中国农业科学，2013，46(20)：4362-4369.
SHI B,DONG S J,ZHU Y M，et al.Advances in study of molecular epidemiology of Porcine epidemic diarrhea virus in China[J].Scientia Agricultura Sinica,2013，46(20)：4362-4369.(in Chinese)
[17] 王妍，赵润泽，谭旭，等.湖北地区猪流行性腹泻病毒流行病学调查及N基因的序列分析[J].中国动物传染病学报，2022，30(4)：135-143.
WANG Y,ZHAO R Z,TAN X，et al.Epidemiological investigation and sequence analysis of N gene of Porcine epidemic diarrhea virus in Hubei province[J].Chinese Journal of Animal Infectious Diseases,2022,30(4)：135-143.(in Chinese)
[18] 李云锋，段滢，梁淳，等.江苏地区猪流行性腹泻流行病学调查及病原S基因序列分析[J].畜牧与兽医，2022，54(5)：90-97.
LI Y F，DUAN Y，LIANG C，et al.Epidemiological investigation on Porcine epidemic diarrhea in Jiangsu province and genetic evolution analysis of the S gene of its pathogen[J].Animal Husbandry ＆ Veterinary Medicine,2022，54(5)：90-97.(in Chinese)
[19] 齐海涛，王利，颜忠，等.2017－2020年华北地区猪流行性腹泻病毒分子流行病学调查[J].黑龙江畜牧兽医，2022，22：91-96.
QI H T，WANG L，YAN Z，et al.Molecular epidemiological survey of Porcine epidemic diarrhea virus in North China from 2017 to 2020[J].Heilongjiang Animal Science and Veterinary Medicine,2022，22：91-96.(in Chinese)
[20] 马思奇，王明，周金法，等.猪流行性腹泻病毒适应 Vero 细胞培养及以传代细胞毒制备氢氧化铝灭活疫苗免疫效力试验[J].中国畜禽传染病，1994，2：15-19.
MA S Q,WANG M,ZHOU J F，et al.Adaption of Porcine epidemic diarrhea virus to growth in cell cultures and efficacy of the killed virus vaccine[J].Chinese Journal of Preventive Veterinary Medicine,1994，2：15-19.(in Chinese)
[21] 郑培，杜久斌，宁慧波，等.猪流行性腹泻灭活疫苗的临床免疫效果评价[J].现代畜牧兽医，2022，1：39-42.
ZHENG P，DU J B,NING H B，et al.Immune effect evaluation of porcine epidemic diarrhea inactivated vaccine[J].Modern Journal of Animal Husbandry and Veterinary Medicine,2022,1：39-42.(in Chinese)
[22] 程杰，栾慧，吴家强，等.猪流行性腹泻新型疫苗的研究进展[J].养猪，2015，4：97-101.
CHENG J，LUAN H，WU J Q，et al.Research progress of new vaccines for porcine epidemic diarrhea[J].Swine Production,2015，4：97-101.(in Chinese)
[23] 佟有恩，冯力，李伟杰，等.猪传染性胃肠炎与猪流行性腹泻二联弱毒疫苗的研究[J].中国预防兽医学报，1999，21(6)：406-410.
TONG Y E，FENG L，LI W J，et al.Development of bi-combined attenuated vaccine against Transmissible gastroenteritis virus and Porcine epidemic diarrhea virus[J].Chinese Journal of Preventive Veterinary Medicine,1999,21(6)：406-410.(in Chinese)
[24] SONG D S，OH J S，KANG B K，et al.Oral efficacy of Vero cell attenuated Porcine epidemic diarrhea virus DR13 strain[J].Research in Veterinary Science，2007，82(1)：134-140.
[25] SINGH G，SINGH P，PILLATZKI A，et al.A minimally replicative vaccine protects vaccinated piglets against challenge with the Porcine epidemic diarrhea virus[J].Frontiers in Veterinary Science，2019，6：347.
[26] 尹宝英，朱小甫，郑红青，等.猪流行性腹泻病毒逃逸宿主天然免疫研究进展[J].动物医学进展，2023，44(10)：89-94.
YIN B Y,ZHU X F,ZHENG H Q，et al.Progress on Porcine epidemic diarrhea virus escaping from host innate immunity[J].Progress in Veterinary Medicine，2023，44(10)：89-94.(in Chinese)
[27] DENG X F，BUCKLEY A C，PILLATZKI A，et al.Inactivating three interferon antagonists attenuates pathogenesis of an enteric Coronavirus[J].Journal of Virology，2020，94(17):e00565-20.
[28] WANG H N，ZHANG L B，SHANG Y B，et al.Emergence and evolution of highly pathogenic Porcine epidemic diarrhea virus by natural recombination of a low pathogenic vaccine isolate and a highly pathogenic strain in the spike gene[J].Virus Evolution，2020，6(2)：49.
[29] 景鼎鼎，朱春华，肖方南，等.猪流行性腹泻病毒疫苗研究进展[J].中国兽医学报，2022，42(10)：2117-2124.
JING D D，ZHU C H，XIAO F N，et al.Research progress on Porcine epidemic diarrhea virus vaccine[J].Chinese Journal of Veterinary Science，2022，42(10)：2117-2124.(in Chinese)
[30] CHANG S H，BAE J L，KANG T J，et al.Identification of the epitope region capable of inducing neutralizing antibodies against the Porcine epidemic diarrhea virus[J].Molecules and Cells，2002，14(2)：295-299.
[31] LI Q N，XU Z C，WU T T，et al.A flagellin-adjuvanted PED subunit vaccine improved protective efficiency against PEDV variant challenge in pigs[J].Vaccine，2018，36(29)：4228-4235.
[32] SYOMIN B V，ILYIN Y V.Virus-like particles as an instrument of vaccine production[J].Molecular Biology，2019，53(3)：323-334.
[33] HSU C W，CHANG M H，CHANG H W，et al.Parenterally administered Porcine epidemic diarrhea virus-like particle-based vaccine formulated with CCL25/28 chemokines induces systemic and mucosal immune protectivity in pigs[J].Viruses，2020，12(10)：1122.
[34] KIM J，YOON J，PARK J E.Construction of Porcine epidemic diarrhea virus-like particles and its immunogenicity in mice[J].Vaccines，2021，9(4)：370.
[35] CHEN Y F，ZHANG Z B，LI J，et al.Porcine epidemic diarrhea virus S1 protein is the critical inducer of apoptosis[J].Virology Journal，2018，15(1)：170.
[36] YU J S，SREENIVASAN C，UPRETY T，et al.Piglet immunization with a spike subunit vaccine enhances disease by Porcine epidemic diarrhea virus[J].NPJ Vaccines，2021，6(1)：22.
[37] 梁雨萱，庞胜美，刘梅，等.猪流行性腹泻疫苗研究进展[J].河南农业科学，2023，52(8)：1-10.
LIANG Y X，PANG S M，LIU M，et al.Research progress of porcine epidemic diarrhea vaccine for pigs[J].Journal of Henan Agricultural Sciences，2023，52(8)：1-10.(in Chinese)
[38] CHANG C Y，HSU W T，CHAO Y C，et al.Display of Porcine epidemic diarrhea virus spike protein on Baculovirus to improve immunogenicity and protective efficacy[J].Viruses，2018，10(7)：346.
[39] YUAN X M，LIN H X，LI B，et al.Efficacy and immunogenicity of recombinant Swinepox virus expressing the truncated S protein of a novel isolate of Porcine epidemic diarrhea virus[J].Archives of Virology，2017，162(12)：3779-3789.
[40] KE Y，YU D Y，ZHANG F Q，et al.Recombinant Vesicular stomatitis virus expressing the spike protein of genotype 2b Porcine epidemic diarrhea virus:A platform for vaccine development against emerging epidemic isolates[J].Virology，2019，533：77-85.
[41] LI X W，ZHANG B Z，ZHANG D S，et al.The construction of recombinant Lactobacillus casei vaccine of PEDV and its immune responses in mice[J].BMC Veterinary Research，2021，17(1)：184.
[42] WANG J L，HUANG L L，MOU C X，et al.Mucosal immune responses induced by oral administration recombinant Bacillus subtilis expressing the COE antigen of PEDV in newborn piglets[J].Bioscience Reports，2019，39(3)：BSR20182028.
[43] 陈裴.猪流行性腹泻病毒S1截短体表面展示酿酒酵母菌株的构建及其生物学特性研究[D].天津：天津大学，2018.
CHEN P.Construction and biological characteristics of recombinant Saccharomyces cerevisiae displaying truncated S1 of Porcine epidemic diarrhea virus[D].Tianjin：Tianjin University,2018.(in Chinese)
[44] TIEN N Q，YANG M S，JANG Y S，et al.Systemic and oral immunogenicity of Porcine epidemic diarrhea virus antigen fused to Poly-Fc of immunoglobulin G and expressed in ΔXT/FT nicotiana benthamiana plants[J].Frontiers in Pharmacology，2021，12：653064.
[45] HO T T，NGUYEN G T，PHAM N B，et al.Plant-derived trimeric CO-26K-equivalent epitope induced neutralizing antibodies against Porcine epidemic diarrhea virus[J].Frontiers in Immunology，2020，11：2152.
[46] 刘晓琳，张传健，郭仕琦，等.猪流行性腹泻新型疫苗的研究进展[J/OL].中国动物传染病学报，1-10.Doi：10.19958/j.cnki.cn31-2031/s.20211126.006.
LIU X L，ZHANG C J,GUO S Q，et al.Research progress of new vaccine for porcine epidemic diarrhea[J].Chinese Journal of Animal Infectious Diseases，1-10.Doi：10.19958/j.cnki.cn31-2031/s.20211126.006.(in Chinese)
[47] FAHAD S，KHAN F A，PANDUPUSPITASARI N S，et al.Recent developments in therapeutic protein expression technologies in plants[J].Biotechnology Letters，2015，37(2)：265-279.
[48] YIN Y，ZHU L，LIU P J，et al.Evaluation on the efficacy and immunogenicity of recombinant DNA plasmids expressing S gene from Porcine epidemic diarrhea virus and VP7 gene from Porcine rotavirus[J]. Brazilian Journal of Microbiology，2019，50(1)：279-286.
[49] ZHANG Y D，ZHANG X H，LIAO X D，et al.Construction of a bivalent DNA vaccine co-expressing S genes of Transmissible gastroenteritis virus and Porcine epidemic diarrhea virus delivered by attenuated Salmonella Typhimurium[J].Virus Genes，2016，52(3)：354-364.
[50] MENG F D，REN Y D，SUO S，et al.Evaluation on the efficacy and immunogenicity of recombinant DNA plasmids expressing spike genes from Porcine transmissible gastroenteritis virus and Porcine epidemic diarrhea virus[J].PLoS One，2013，8(3)：e57468.
[51] 杨利敏，王俊虹，徐明国，等.猪流行性腹泻mRNA疫苗的制备与免疫原性评价[J].生物工程学报，2023，39(7):2624-2633.
YANG L M，WANG J H，XU M G，et al.Preparation and immunogenicity evaluation of mRNA vaccine against Porcine epidemic diarrhea[J].Chinese Journal of Biotechnology，2023，39(7)：2624-2633.(in Chinese)
[52] YAN Z P，YANG M，LAI C L.COVID-19 vaccines:A review of the safety and efficacy of current clinical trials[J].Pharmaceuticals (Basel,Switzerland)，2021，14(5)：406.
[53] SHAN Y，LIU Z Q，LI G W，et al.Nucleocapsid protein from Porcine epidemic diarrhea virus isolates can antagonize interferon-λ production by blocking the nuclear factor-κB nuclear translocation[J].Journal of Zhejiang University-Science B (Biomedicine & Biotechnology)，2018,19(7)：570-580.