猪圆环病毒2型疫苗的研究进展

摘要/Abstract

摘要： 猪圆环病毒2型（PCV2）是引起断奶仔猪多系统衰竭综合征（PMWS）的主要病原，给全球养猪业造成了巨大经济损失。PCV2感染可以破坏动物机体的免疫系统，造成严重的免疫抑制，容易诱发多种细菌及病毒的混合感染与继发感染，给疾病的诊断和治疗带来巨大的困难。疫苗免疫接种是防控PCV2感染的有效手段，有关PCV2疫苗的研究已成为国内外学者的关注热点。迄今为止，欧美几家跨国公司已先后推出商品化的PCV2灭活疫苗、亚单位疫苗及嵌合病毒疫苗，国内也已研制出PCV2灭活疫苗，这些疫苗的推广应用为有效防控猪圆环病毒病发挥了重要作用。鉴于这些疫苗尚不能完全阻断PCV2传播，无法彻底清除体内感染的病毒，因此，开发高效、价廉的新型活载体疫苗、核酸疫苗及标记疫苗是今后研究的趋势。笔者在本文中概括地介绍了目前商品化的PCV2疫苗的特性和免疫效力，并对近年来有关PCV2活载体疫苗、核酸疫苗及标记疫苗等新型疫苗的研究进展进行综述，以期为猪圆环病毒病的防制提供参考。

关键词: 猪圆环病毒2型, 疫苗, 研究

Abstract: Porcine circovirus type 2 (PCV2) has been recognized as the primary causative agent of postweaning multisystemic wasting syndrome (PMWS), which results in tremendous economic losses in swine industry worldwide. PCV2 infection leads to impaired immune system in animals, severe immunosuppression, as well as co-infection and secondary infection among various bacteria and viruses, which will bring about tremendous obstacles in diagnosis and therapy. It is an effective way to control PCV2 infection by vaccination. The study on PCV2 vaccines is one of the hot research areas. To date, the inactivated vaccines of PCV2, subunit vaccines and chimeric virus vaccines are commercially available in North America and Europe, and the inactivated vaccines of PCV2 have also been developed in China. Development and application of the commercial PCV2 vaccines play a significant role in the prevention and control of PCV2 associated diseases effectively. However, the commercial PCV2 vaccines could not totally block the transmission of PCV2 among pigs and eliminate the virus in pigs. Therefore, it is the main research trend to develop efficient and inexpensive genetically engineered vaccines such as live vector vaccines, DNA vaccines and marker vaccines in the future. This article summarizes the characteristics and efficacy of currently commercial PCV2 vaccines, and reviews the recent achievements on PCV2 vaccines including live vector vaccines, DNA vaccines and marker vaccines. It may become a useful contributor to the next generation vaccines for control of PCV2-associated diseases.

Key words: porcine circovirus type 2, vaccines, research

中图分类号:

S858.285.3

王一平, 郭龙军, 唐青海, 刘长明. 猪圆环病毒2型疫苗的研究进展[J]. 畜牧兽医学报, 2012, 43(9): 1337-1345.

WANG Yi-Ping, GUO Long-Jun, TANG Qing-Hai, LIU Chang-Ming. Research Progress on Vaccines of Porcine Circovirus Type 2[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2012, 43(9): 1337-1345.

参考文献

［1］ALLAN G M，ELLIS J A. Porcine circoviruses：A review ［J］. Vet Diagn Invest，2000，12：3-14.

［2］GUO L J，LU Y H，WEI Y W，et al. Porcine circovirus type 2 (PCV2)：genetic variation and newly emerging genotypes in China ［J］. Virol J，2010，7（1）：273.

［3］SEGALES J，ALLAN G M，DOMINGO M. Porcine circovirus diseases ［J］. Anim Health Res Rev，2005，6（2）：119-142.

［4］TISCHER I，GELDERBLOM H，VETTERMANN W，et al. A very small porcine virus with circular single-stranded DNA ［J］. Nature，1982，295：64-66.

［5］CHEUNG A K. Transcriptional analysis of porcine circovirus Type 2 ［J］. Virology，2003，305（1）：168-180.

［6］NAWAGITGUL P，MOROZOW I，BOLIN S R，et al. Open reading frame 2 of porcine circovirus type 2 encodes a major capsid protein ［J］. J Gen Virol，2000，81（9）：2281-2287.

［7］LIU J，CHEN I，KWANG J. Characterization of a previously unidentified viral protein in porcine circovirus type 2-infected cells and its role in virus-induced apoptosis ［J］. J Virol，2005，79（13）：8262-8274.

［8］RAMAMOORTHY S，MENG X J. Porcine circoviruses：a minuscule yet mammoth paradox ［J］. Anim Health Res Rev，2009，10（1）：1-20.

［9］OPRIESSNIG T，MENG X J，HALBUR P G. Porcine circovirus type 2 associated disease：update on current terminology，clinical manifestations，pathogenesis，diagnosis，and intervention strategies ［J］. J Vet Diagn Invest，2007，19：591-615.

［10］KEKARAINEN T，MCCULLOUGH K，FORT M，et al. Immune responses and vaccine-induced immunity against Porcine circovirus type 2 ［J］. Vet Immunol Immunop，2010，136：185-193.

［11］BEACH N M，MENG X J. Efficacy and future prospects of commercially available and experimental vaccines against porcine circovirus type 2 (PCV2) ［J］. Virus Res，2012，164：33-42.

［12］OPRIESSNIG T，PATTERSON A R，MADSON D M，et al. Comparison of the effectiveness of passive (dam) versus active (piglet) immunization against porcine circovirus type 2 (PCV2) and impact of passively derived PCV2 vaccineinduced immunity on vaccination ［J］. Vet Microbiol，2010，142：177-183.

［13］KURMANN J，SYDLER T，BRUGNERA E，et al. Vaccination of dams increases antibody titer and improves growth parameters in finisher pigs subclinically infected with porcine circovirus type 2 ［J］. Clin Vaccine Immunol，2011，18（10）：1644-1649.

［14］FENAUX M，OPRIESSNIG T，HALBUR P G，et al. Two amino acid mutations in the capsid protein of type 2 porcine circovirus (PCV2) enhanced PCV2 replication in vitro and attenuated the virus in vivo ［J］. J Virol，2004，78（24）：13440-13446.

［15］OPRIESSNIG T，PATTERSON A R，MADSON D M，et al. Comparison of efficacy of commercial one dose and two dose PCV2 vaccines using a mixed PRRSV-PCV2-SIV clinical infection model 2-3 months post vaccination ［J］. Vaccine，2009，27：1002-1007.

［16］FORT M，SIBILA M，PREZMARTN E，et al. One dose of a porcine circovirus 2 (PCV2) subunit vaccine administered to 3-week-old conventional piglets elicits cellmediated immunity and significantly reduces PCV2 viremia in an experimental model ［J］. Vaccine，2009，27（30）：4031-4037.

［17］刘长明，陆月华，张超范，等. 猪圆环病毒2型重组Cap蛋白在昆虫杆状病毒中的表达［J］.中国预防兽医学报，2005，27（6）：479-482.

［18］张家明. 猪圆环病毒2型ORF2基因在昆虫杆状病毒表达系统的表达及亚单位疫苗的初步研究［D］. 郑州：河南农业大学，2010.

［19］WESLEY R D，TANG M，LAGER K M. Protection of weaned pigs by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of H3N2 swine influenza virus ［J］. Vaccine，2004，22（34）：27-34.

［20］CHINSANGARAM J，MORAES M P，KOSTER M，et al. Novel viral disease control strategy：adenovirus expressing alpha interferon rapidly protects swine from foot-and-mouth disease ［J］. J Virol，2003，77（162）：1-5.

［21］MASCOLA J R，SAMBOR A，BEAUDRY K，et al. Neutralizing antibodies elicited by immunization of monkeys with DNA plasmids and recombinant adenoviral vectors expressing human immunodeficiency virus type 1 proteins ［J］. J Virol，2005，79（77）：1-9.

［22］WANG X W，JIANG W M，JIANG P，et al. Construction and immunogenicity of recombinant adenovirus expressing the capsid protein of porcine circovirus 2 ( PCV2) in mice ［J］. Vaccine，2006，24(16)：3374-3380.

［23］WANG X W，JIANG P，LI Y，et al. Protection of pigs against post-weaning multisystemic wasting syndrome by a recombinant adenovirus expressing the capsid protein of porcine circovirus type 2 ［J］. Vet Microbiol，2007，121（324）：215-224.

［24］LIU G M，LUO M L，CHEN R A，et al. Construction and immunogenicity of recombinant adenovirus expressing ORF2 of PCV2 and porcine IFN-gamma ［J］. Vaccine，2011，29：8677-8682.

［25］JU C，FAN H Y，TAN Y，et al. Immunogenicity of a recombinant pseudorabies virus expressing ORF1-ORF2 fusion protein of porcine circovirus type 2 ［J］. Vet Microbiol，2005，109：179-190.

［26］SONG Y F，JIN M L，ZHANG S L，et al. Generation and immunogenicity of a recombinant pseudorabies virus expressing cap protein of porcine circovirus type 2 ［J］. Vet Microbiol，2007，119：97-104.

［27］FAN Y，XIAO S，FANG L，et al. Efficient transduction of porcine kidney cells with pseudotype baculovirus ［J］. J Huazhong Agric Univ，2007，26：478-481.

［28］FAN H Y，PAN Y H，FANG L R，et al. Construction and immunogenicity of recombinant pseudotype baculovirus expressing the capsid protein of porcine circovirus type 2 in mice ［J］. J Virol Methods，2008，150：21-26.

［29］PEI Y L，HODGINS D C，WU J Q，et al. Porcine reproductive and respiratory syndrome virus as a vector：Immunogenicity of green fluorescent protein and porcine circovirus type 2 capsid expressed from dedicated subgenomic RNAs ［J］. Virology，2009，389（122）：91-99.

［30］GAO J M，WANG Y L，LIU Z Q，et al. Phage display and its application in vaccine design ［J］. Ann Microbiol，2010，60：13-19.

［31］GAMAGE L N，ELLIS J，HAYES S. Immunogenicity of bacteriophage lambda particles displaying porcine Circovirus 2 (PCV2) capsid protein epitopes ［J］.Vaccine，2009，27（47）：6595-6604.

［32］DROUAULT S，CORTHIER G，EHRLICH S D，et al. Survival，physiology and lysis of Lactococcus lactis in the digestive tract ［J］. Appl Environ Microbiol，1999，65（11）：4881-4886.

［33］WANG K，HUANG L H，KONG J，et al. Expression of the capsid protein of porcine circovirus type 2 in Lactococcus lactis for oral vaccination ［J］. J Virol Methods，2008，150：1-6.

［34］STEVENSON A，ROBERTS M. Intranasal immunisation against tetanus with an attenuated Bordetella bronchiseptica vector expressing FrgC：improved immunogenicity using a Bvg-regulated promoter to express FrgC ［J］. Vaccine，2004，22：4300-4305.

［35］KIM T，TOAN N T，SEO J，et al. Bordetella bronchiseptica aroA mutant as a live vaccine vehicle for heterologous porcine circovirus type 2 major capsid protein expression ［J］. Vet Microbiol，2009，138：318-324.

［36］BUCAREY S A，NORIEGA J，REYES P，et al. The optimized capsid gene of porcine circovirus type 2 expressed in yeast forms virus-like particles and elicits antibody responses in mice fed with recombinant yeast extracts ［J］. Vaccine，2009，27：5781-5790.

［37］KAMSTRUP S，BARFOED A M，FRIMANN T H，et al. Immunisation against PCV2 structural protein by DNA vaccination of mice ［J］. Vaccine，2004，22：1358-1361.

［38］BLANCHARD P，MAHE D，CARIOLET R，et al. Protection of swine against post-weaning multisystemic wasting syndrome (PMWS) by porcine circovirus type 2 (PCV2) proteins ［J］. Vaccine，2003，21（31）：4565-4575.

［39］SHEN H G，ZHOU J Y，HUANG Z Y，et al. Protective immunity against porcine circovirus 2 by vaccination with ORF2-based DNA and subunit vaccines in mice ［J］. J Gen Virol，2008，89：1857-1865.

［40］FENAUX M，OPRIESSNIG T，HALBUR P G，et al. A chimeric porcine circovirus (PCV) with the immunogenic capsid gene of the pathogenic PCV type 2 (PCV2) cloned into the genomic backbone of the nonpathogenic PCV1 induces protective immunity against PCV2 infection in pigs ［J］. J Virol，2004，78（12）：6297-6303.

［41］ARAVINDARAM K，KUO T Y，LAN C W，et al. Protective immunity against porcine circovirus 2 in mice induced by a genebased combination vaccination ［J］. J Gene Med，2009，11（4）:288301.

［42］SEGALS J，URNIZA A，ALEGRE A，et al. A genetically engineered chimeric vaccine against porcine circovirus type 2 (PCV2) improves clinical，pathological and virological outcomes in postweaning multisystemic wasting syndrome affected farms ［J］. Vaccine，2009，27：7313-7321.

［43］OPRIESSNIG T，PATTERSON A R，ELSENER J，et al. Influence of maternal antibodies on efficacy of porcine circovirus type 2 (PCV2) vaccination to protect pigs from experimental infection with PCV2 ［J］. Clin Vaccine Immunol，2008，15（3）：397-401.

［44］OPRIESSNIG T，MADSON D M，PRICKETT J R，et al. Effect of porcine circovirus type 2 (PCV2) vaccination on porcine reproductive and respiratory syndrome virus (PRRSV) and PCV2 coinfection ［J］. Vet Microbiol，2008，131：103-114.

［45］LIU X J，WANG X B，SONG Y，et al. A candidate inactivated chimeric vaccine PCV1-2 constructed based on PCV1 and PCV2 isolates originating in China and its evaluation in conventional pigs in regard to protective efficacy against PCV2 infection ［J］. Microbiol Immunol，2011，55：254-266.

［46］BEACH N M，SMITH S M，RAMAMOORTHY S，et al. Chimeric porcine circoviruses (PCV) containing amino acid epitope tags in the C terminus of the capsid gene are infectious and elicit both antiepitope tag antibodies and anti-PCV type 2 neutralizing antibodies in pigs ［J］. J Virol，2011，85（9）：4591-4595.

［47］HUANG L P，LU Y H，WEI Y W，et al. Construction and biological characterisation of recombinant porcine circovirus type 2 expressing the V5 epitope tag ［J］. Virus Res，2011，161（2）：115-123.

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