猪圆环病毒病疫苗研究进展

Advances in the vaccines against porcine circovirus disease

摘要

猪圆环病毒病(PCVAD)是危害养猪业的重要疫病之一，可引起免疫抑制和继发感染，已经造成严重经济损失。猪圆环病毒(PCV)有 4 个种。猪圆环病毒 2 型(PCV2)有 9 种基因型，其中 PCV2d 为我国目前优势流行毒株，免疫接种是防控该病的关键手段。本文系统综述了 PCV2 疫苗的研究进展，重点介绍了病毒灭活疫苗、基于不同表达系统的亚单位疫苗、合成肽疫苗和基因工程活载体疫苗等的研发与应用现状，梳理了 PCV2 多基因型联合疫苗及其与其他病原联合疫苗的研发和应用效果，探讨了基于 Cap 重组蛋白病毒样颗粒纳米展示平台的疫苗设计新策略，指出了目前猪圆环病毒商品疫苗存在的缺陷及未来疫苗研究方向。

Abstract

Porcine circovirus-associated disease (PCVAD) is one of the most important infectious diseases, which causing immunosuppression of pigs resulting in multiple secondary infection diseases, and significant economic losses to the global swine industry. Currently, it has been reported that porcine circoviruses have at least four species. And porcine circovirus type 2 (PCV2) has nine genotypes, among which PCV2d is the predominant circulating strain in China. PCV2 vaccination remains the key strategy for controlling this disease. This review systematically summarizes the research progress on PCV2 vaccines, focusing on the development and application of inactivated vaccines, subunit vaccines based on different expression systems, synthetic peptide vaccines, and genetically engineered live vector vaccines. It also outlines the development and efficacy of multigenotype PCV2 vaccines and combined vaccines with other pathogens, including the novel vaccine design strategies based on the Cap recombinant protein virus-like particle nano-display platform. And it also highlights the limitations of the current commercial PCV vaccines and future directions for new vaccine research.

关键词

猪圆环病毒病 / 疫苗 / 免疫防控

Key words

Keywords:porcine circovirus disease / vaccine / immunological control

参考文献

[1] Franzo G, Segalés J. Porcine circovirus 2 genotypes, immunity and vaccines: multiple genotypes but one single serotype[J]. Pathogens, 2020, 9(12): 1049.

[2] Opriessnig T, Gomes-Neto JC, Hemann M, et al. An experimental live chimeric porcine circovirus 1-2a vaccine decreases porcine circovirus 2b viremia when administered intramuscularly or orally in a porcine circovirus 2b and porcine reproductive and respiratory syndrome virus dual-challenge model: efficacy of a live chimeric PCV2 vaccine[J]. Microbiology and Immunology, 2011, 55(12): 863-873.

[3] Palinski R, Piñeyro P, Shang PC, et al. A novel porcine circovirus distantly related to known circoviruses is associated with porcine dermatitis and nephropathy syndrome and reproductive failure[J]. Journal of Virology, 2017, 91(1): e01879-e01816.

[4] Zhang HH, Hu WQ, Li JY, et al. Novel circovirus species identified in farmed pigs designated as porcine circovirus 4, Hunan Province, China[J]. Transboundary and Emerging Diseases, 2020, 67(3): 1057-1061.

[5] Shi TF, Du Q, Kang JS, et al. PCV2 infection represses the differentiation of light zone germinal center B cells by inhibiting their interaction with helper cells[J]. Microorganisms, 2025, 13(9): 2184.

[6] Fehér E, Jakab F, Bányaí K. Mechanisms of circovirus immunosuppression and pathogenesis with a focus on porcine circovirus 2: a review[J]. Veterinary Quarterly, 2023, 43(1): 1-18.

[7] Jiang RJ, Huang QY, Shen RT, et al. PCV2 infection induces the differentiation of Treg cells via the TGF-β/Smad3 pathway[J]. MBio, 2025, 16(9): e01366-e01325.

[8] Karuppannan AK, Opriessnig T. Porcine circovirus type 2 (PCV2) vaccines in the context of current molecular epidemiology[J]. Viruses, 2017, 9(5): 99.

[9] Meng XJ. Porcine circovirus type 2 (PCV2): pathogenesis and interaction with the immune system[J]. Annual Review of Animal Biosciences, 2013, 1: 43-64.

[10] Opriessnig T, Xiao CT, Halbur PG, et al. A commercial porcine circovirus (PCV) type 2a-based vaccine reduces PCV2d viremia and shedding and prevents PCV2d transmission to naive pigs under experimental conditions[J]. Vaccine, 2017, 35(2): 248-254.

[11] Wongchanapai P, Yamsakul P, Arunorat J, et al. Comparative efficacy of chimeric porcine circovirus (PCV) vaccines against experimental heterologous PCV2d challenges[J]. Veterinary Sciences, 2023, 10(2): 80.

[12] Yang K, Li WT, Niu HH, et al. Efficacy of single dose of an inactivated porcine circovirus type 2 (PCV2) whole-virus vaccine with oil adjuvant in piglets[J]. Acta Veterinaria Scandinavica, 2012, 54(1): 67.

[13] Hirai T, Nunoya T, Ihara T, et al. Infectivity of porcine circovirus 1 and circovirus 2 in primary porcine hepatocyte and kidney cell cultures[J]. The Journal of Veterinary Medical Science, 2006, 68(2): 179-182.

[14] 陈念劬， 王先炜， 李玉峰， 等. 适合猪圆环病毒 2 型敏感复制的 PK15 细胞株的克隆与鉴定[J]. 中国兽医科学， 2011， 41(1): 14-18.

[15] Chen NQ, Wang XW, Li YF, et al. Cloning and identification of PK15 cells for the sensitive replication of porcine circovirus 2[J]. Chinese Veterinary Science, 2011, 41(1): 14-18(in Chinese with English abstract).

[16] Wang XW, Jiang WM, 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.

[17] Song YF, Jin ML, Zhang SL, et al. Generation and immunogenicity of a recombinant pseudorabies virus expressing cap protein of porcine circovirus type 2[J]. Veterinary Microbiology, 2007, 119(2/3/4): 97-104.

[18] Shen HG, Zhou JY, Huang ZY, et al. Protective immunity against porcine circovirus 2 by vaccination with ORF2-based DNA and subunit vaccines in mice[J]. The Journal of General Virology, 2008, 89(8): 1857-1865.

[19] Yin SH, Sun SQ, Yang SL, et al. Self-assembly of virus-like particles of porcine circovirus type 2 capsid protein expressed from Escherichia coli[J]. Virology Journal, 2010, 7(1): 166.

[20] Martelli P, Ferrari L, Morganti M, et al. One dose of a porcine circovirus 2 subunit vaccine induces humoral and cell-mediated immunity and protects against porcine circovirus-associated disease under field conditions[J]. Veterinary Microbiology, 2011, 149(3/4): 339-351.

[21] Haake M, Palzer A, Rist B, et al. Influence of age on the effectiveness of PCV2 vaccination in piglets with high levels of maternally derived antibodies[J]. Veterinary Microbiology, 2014, 168(2/3/4): 272-280.

[22] Pleguezuelos P, Sibila M, Cuadrado R, et al. Exploratory field study on the effects of porcine circovirus 2 (PCV-2) sow vaccination at different physiological stages mimicking blanket vaccination[J]. Porcine Health Management, 2021, 7(1): 35.

[23] Caspari K, Henning H, Schreiber F, et al. Impact of porcine circovirus type 2 (PCV2) vaccination on boar semen quality and quantity using two different vaccines[J]. Theriogenology, 2014, 82(4): 574-579.

[24] Masuda A, Lee JM, Miyata T, et al. Purification and characterization of immunogenic recombinant virus-like particles of porcine circovirus type 2 expressed in silkworm pupae[J]. The Journal of General Virology, 2018, 99(7): 917-926.

[25] Wu PC, Chen TY, Chi JN, et al. Efficient expression and purification of porcine circovirus type 2 virus-like particles in Escherichia coli[J]. Journal of Biotechnology, 2016, 220: 78-85.

[26] Xi XF, Mo XB, Xiao Y, et al. Production of Escherichia coli-based virus-like particle vaccine against porcine circovirus type 2 challenge in piglets: structure characterization and protective efficacy validation[J]. Journal of Biotechnology, 2016, 223: 8-12.

[27] Wang ND, Zhang Y, Lei XN, et al. Optimized conditions for preserving stability and integrity of porcine circovirus type 2 virus-like particles during long-term storage[J]. Journal of Virological Methods, 2017, 243: 146-150.

[28] Li YY, Lin Y, Xin G, et al. Comparative evaluation of ELPlated virus-like particle vaccine with two commercial PCV2 vaccines by experimental challenge[J]. Vaccine, 2020, 38(23): 3952-3959.

[29] Li YY, Wang YJ, Cheng J, et al. Generation and immunogenicity assessment of ELPlated virus-like particles of porcine circovirus type 2[J]. Virology Journal, 2020, 17(1): 72.

[30] Zhang CX, He F, Li NF, et al. Optimized production of full-length PCV2d virus-like particles in Escherichia coli: a cost-effective and high-yield approach for potential vaccine antigen development[J]. Microbial Pathogenesis, 2024, 190: 106630.

[31] 张晓勇， 郑其升， 魏雪涛， 等. 猪圆环病毒Ⅱ型 ORF2 基因在酵母中的高效分泌表达[J]. 中国病毒学， 2005(2): 125-129.

[32] Zhang XY, Zheng QS, Wei XT, et al. High level secretory expression of the ORF2 gene of porcine circovirus in yeast[J]. Virologica Sinica, 2005(2): 125-129(in Chinese with English abstract).

[33] Chen P, Zhang L, Chang N, et al. Preparation of virus-like particles for porcine circovirus type 2 by Yeast Fab assembly[J]. Virus Genes, 2018, 54(2): 246-255.

[34] Duan JK, Yang DQ, Chen L, et al. Efficient production of porcine circovirus virus-like particles using the nonconventional yeast Kluyveromyces marxianus[J]. Applied Microbiology and Biotechnology, 2019, 103(2): 833-842.

[35] Park Y, Min K, Kim NH, et al. Porcine circovirus 2 capsid protein produced in N. benthamiana forms virus-like particles that elicit production of virus-neutralizing antibodies in guinea pigs[J]. New Biotechnology, 2021, 63: 29-36.

[36] Park KH, Cho H, Suh J, et al. Field evaluation of novel plant-derived porcine circovirus type 2 vaccine related to subclinical infection[J]. Veterinary Medicine and Science, 2023, 9(6): 2703-2710.

[37] Deng YY, Sheng YM, Zhang GX, et al. A novel strategy for an anti-idiotypic vaccine: nanobody mimicking neutralization epitope of porcine circovirus type 2[J]. Journal of Virology, 2024, 98(2): e0165023.

[38] Mo XB, Li XD, Yin B, et al. Structural roles of PCV2 capsid protein N-terminus in PCV2 particle assembly and identification of PCV2 type-specific neutralizing epitope[J]. PLoS Pathogens, 2019, 15(3): e1007562.

[39] Zhan Y, Yu WT, Cai X, et al. The carboxyl terminus of the porcine circovirus type 2 capsid protein is critical to virus-like particle assembly, cell entry, and propagation[J]. Journal of Virology, 2020, 94(9): e00042-e00020.

[40] Wang DL, Zhang SJ, Zou YW, et al. Structure-based design of porcine circovirus type 2 chimeric VLPs (cVLPs) displays foreign peptides on the capsid surface[J]. Frontiers in Cellular and Infection Microbiology, 2018, 8: 232.

[41] Luo QP, Ahmed W, Dai YC, et al. Evaluation of a virus-like nanoparticle porcine circovirus type-2 (PCV2) capsid protein fused with the pig immunoglobulin fc fragment as a novel vaccine candidate against PCV2 in mice[J]. Vaccines, 2021, 9(10): 1128.

[42] Jin J, Park C, Cho SH, et al. The level of decoy epitope in PCV2 vaccine affects the neutralizing activity of sera in the immunized animals[J]. Biochemical and Biophysical Research Communications, 2018, 496(3): 846-851.

[43] 黄立平， 刘长明， 危艳武， 等. 抗猪圆环病毒 2 型 Cap 蛋白中和性单克隆抗体的制备及鉴定[J]. 中国预防兽医学报， 2009， 31(2): 132-136.

[44] Huang LP, Liu CM, Wei YW, et al. Preparation and identification of neutralizing monoclonal antibody to the recombinant capsid protein of porcine circovirus type 2[J]. Chinese Journal of Preventive Veterinary Medicine, 2009, 31(2): 132-136(in Chinese with English abstract).

[45] 曹彦琼. 猪圆环病毒 2 型 Cap 蛋白单克隆抗体的制备与鉴定[D]. 南京: 南京农业大学， 2010: 10-23.

[46] Cao YQ. Preparation and identification of monoclonal antibodies against porcine circovirus type 2 Cap protein[D]. Nanjing: Nanjing Agricultural University, 2010(in Chinese with English abstract).

[47] 翟淑燕. 猪圆环病毒 2 型单克隆抗体研制与夹心 ELISA 抗原检测方法的建立[D]. 南京: 南京农业大学， 2013: 11-16.

[48] Zhai SY. Development of monoclonal antibodies against porcine circovirus type 2 and establishment of a sandwich ELISA for antigen detection[D]. Nanjing:Nanjing Agricultural University, 2013(in Chinese with English abstract).

[49] Jeong J, Park C, Kim S, et al. Evaluation of the efficacy of a novel porcine circovirus type 2 synthetic peptide vaccine[J]. Revue Canadienne de Recherche Veterinaire, 2018, 82(2): 146-153.

[50] 吴胜昔， 曾政， 蔡家利， 等. 猪圆环病毒 2 型 CAP 蛋白新型表位抗原肽的设计、合成及免疫原性研究[J]. 免疫学杂志， 2014， 30(5): 397-401.

[51] Wu SX, Zeng Z, Cai JL, et al. Studies on molecular design, chemical synthesis and immunogenicity of novel antigenic peptides against the capsid protein of porcine circovirus type 2[J]. Immunological Journal, 2014, 30(5): 397-401(in Chinese with English abstract).

[52] 姜平， 白娟. 一种猪圆环病毒 2 型免疫保护多肽与疫苗:CN201410318980.X[P]. 2017-06-27.

[53] Jiang P, Bai J. An immunoprotective polypeptide against porcine circovirus type 2 and its vaccine:CN201410318980. X[P]. 2017-06-27(in Chinese).

[54] 栗利芳， 贾淼， 王楠， 等. 一种猪圆环合成肽疫苗及其制备方法和应用:CN201610754866.0[P]. 2019-07-26.

[55] Li LF, Jia M, Wang N, et al. A porcine circovirus synthetic peptide vaccine and its preparation method and application:CN201610754866.0[P]. 2019-07-26(in Chinese).

[56] 栗利芳， 贾淼， 刘新月， 等. 猪圆环合成肽疫苗及其制备方法和应用:CN201710054285.0[P]. 2020-08-25.

[57] Li LF, Jia M, Liu XY, et al. Circular peptide vaccine for pigs and its preparation method and application:CN201710054285.0[P]. 2020-08-25(in Chinese).

[58] Li DL, Huang Y, Du Q, et al. CD40 ligand and GMCSF coexpression enhance the immune responses and protective efficacy of PCV2 adenovirus vaccine[J]. Viral Immunology, 2016, 29(3): 148-158.

[59] Li DL, Du Q, Wu B, et al. Immunogenicity of adenovirus vaccines expressing the PCV2 capsid protein in pigs[J]. Vaccine, 2017, 35(36): 4722-4729.

[60] Zhang ZC, Luo Y, Zhang YM, et al. Enhanced protective immune response to PCV2 adenovirus vaccine by fusion expression of Cap protein with InvCin pigs[J]. Journal of Veterinary Science, 2019, 20(4): e35.

[61] Wu XF, Wu H, Wang HX, et al. A new strategy to develop pseudorabies virus-based bivalent vaccine with high immunogenicity of porcine circovirus type 2[J]. Veterinary Microbiology, 2021, 255: 109022.

[62] Yang YT, Xu ZW, Tao Q, et al. Construction of recombinant pseudorabies virus expressing PCV2Cap, PCV3Cap, and IL-4: investigation of their biological characteristics and immunogenicity[J]. Frontiers in Immunology, 2024, 15: 1339387.

[63] Lu CH, Chen WJ, Chen H, et al. Immunological characteristics of the recombinant pseudorabies virus with chimeric PCVCap protein in pigs[J]. Veterinary Microbiology, 2025, 305: 110529.

[64] Li H, Zhang JN, Guo RH, et al. Immunogenicity evaluation of a recombinant pseudorabies virus co-expressing PCV2 and PCV3 capsid proteins in mice and piglets[J]. Vaccine, 2025, 60: 127307.

[65] Pavulraj S, Pannhorst K, Stout RW, et al. A triple gene-deleted pseudorabies virus-vectored subunit PCV2b and CSFV vaccine protects pigs against PCV2b challenge and induces serum neutralizing antibody response against CSFV[J]. Vaccines, 2022, 10(2): 305.

[66] Silva E, Medina-Ramirez E, Pavulraj S, et al. A triple gene-deleted pseudorabies virus-vectored subunit PCV2b and CSFV vaccine protect pigs against avirulent CSFV challenge[J]. Viruses, 2023, 15(11): 2143.

[67] Pei YL, Hodgins DC, Wu JQ, 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(1/2): 91-99.

[68] Tian DB, Sooryanarain H, Matzinger SR, et al. Protective efficacy of a virus-vectored multi-component vaccine against porcine reproductive and respiratory syndrome virus, porcine circovirus type 2 and swine influenza virus[J]. Journal of General Virology, 2017, 98(12): 3026-3036.

[69] de Oliveira Daiane Silva DS, Barbosa-Stancioli EF, Coelho-Dos-Reis JGA, et al. Short communication: a modified vaccinia virus ankara-based porcine circovirus 2 vaccine elicits strong antibody response upon prime-boost homologous immunization in a preclinical model[J]. Brazilian Journal of Microbiology, 2020, 51(3): 1439-1445.

[70] Kim T, Toan NT, Seo J, et al. Bordetella bronchiseptica AroA mutant as a live vaccine vehicle for heterologous porcine circovirus type 2 major capsid protein expression[J]. Veterinary Microbiology, 2009, 138(3/4): 318-324.

[71] Xu XG, Zhao HN, Zhang Q, et al. Oral vaccination with attenuated Salmonella enterica serovar Typhimurium expressing Cap protein of PCV2 and its immunogenicity in mouse and swine models[J]. Veterinary Microbiology, 2012, 157(3/4): 294-303.

[72] Lloren KKS, Sivasankar C, Lee JH. Comparative immunogenic and immunoprotective activities of PCV2d Cap and Rep antigens delivered by an efficient eukaryotic expression system engineered into a Salmonella vaccine vector[J]. Veterinary Microbiology, 2024, 295: 110151.

[73] Zhang S, Mou CX, Cao YN, et al. Immune response in piglets orally immunized with recombinant Bacillus subtilis expressing the capsid protein of porcine circovirus type 2[J]. Cell Communication and Signaling, 2020, 18(1): 23.

[74] Wang K, Huang LH, Kong J, et al. Expression of the capsid protein of porcine circovirus type 2 in Lactococcus lactis for oral vaccination[J]. Journal of Virological Methods, 2008, 150(1/2): 1-6.

[75] Wang L, Zhao D, Sun B, et al. Oral vaccination with the porcine circovirus type 2 (PCV-2) capsid protein expressed by Lactococcus lactis induces a specific immune response against PCV-2 in mice[J]. Journal of Applied Microbiology, 2020, 128(1): 74-87.

[76] Fenaux M, Opriessnig T, Halbur PG, 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]. Journal of Virology, 2004, 78(12): 6297-6303.

[77] Kamstrup S, Barfoed AM, Frimann TH, et al. Immunisation against PCV2 structural protein by DNA vaccination of mice[J]. Vaccine, 2004, 22(11/12): 1358-1361.

[78] Shen HG, Zhou JY, Zhang X, et al. Interference of porcine circovirus type 2 ORF2 immunogenicity by ORF1 and ORF3 mixed DNA immunizations in mice[J]. Virology, 2009, 393(1): 104-111.

[79] Aravindaram K, Kuo TY, Lan CW, et al. Protective immunity against porcine circovirus 2 in mice induced by a gene-based combination vaccination[J]. The Journal of Gene Medicine, 2009, 11(4): 288-301.

[80] Fu F, Li XS, Lang YK, et al. Co-expression of Ubiquitin gene and capsid protein gene enhances the potency of DNA immunization of PCV2 in mice[J]. Virology Journal, 2011, 8(1): 264.

[81] Sylla S, Cong YL, Sun YX, et al. Protective immunity conferred by porcine circovirus 2 ORF2-based DNA vaccine in mice[J]. Microbiology and Immunology, 2014, 58(7): 398-408.

[82] Dong B, Feng J, Lin H, et al. Immune responses of mice immunized by DNA plasmids encoding PCV2 ORF2 gene, porcine IL-15 or the both[J]. Vaccine, 2013, 31(48): 5736-5744.

[83] Fu F, Tian HB, Li XS, et al. C-terminal heat shock protein 70 of Mycobacterium tuberculosis as a molecular adjuvant for DNA vaccination with the porcine circovirus type 2 ORF2(capsid)gene in mice[J]. The Veterinary Journal, 2013, 195(2): 244-247.

[84] Hou ZM, Wang HH, Feng YN, et al. A candidate DNA vaccine encoding a fusion protein of porcine complement C3d-P28 and ORF2 of porcine circovirus type 2 induces cross-protective immunity against PCV2b and PCV2d in pigs[J]. Virology Journal, 2019, 16(1): 57.

[85] Gillespie J, Juhan NM, Di Cristina J, et al. A genetically engineered chimeric vaccine against porcine circovirus type 2 (PCV2) is genetically stable in vitro and in vivo[J]. Vaccine, 2008, 26(33): 4231-4236.

[86] Beach NM, Ramamoorthy S, Opriessnig T, et al. Novel chimeric porcine circovirus (PCV) with the capsid gene of the emerging PCV2b subtype cloned in the genomic backbone of the non-pathogenic PCV1 is attenuated in vivo and induces protective and cross-protective immunity against PCV2b and PCV2a subtypes in pigs[J]. Vaccine, 2010, 29(2): 221-232.

[87] Li JZ, Yu TQ, Wang XB, et al. Comparative efficacy of experimental inactivated and live-attenuated chimeric porcine circovirus (PCV)1-2b vaccines derived from PCV1 and PCV2b isolates originated in China[J]. Virology Journal, 2015, 12(1): 113.

[88] Huan CC, Fan MY, Cheng QR, et al. Evaluation of the efficacy and cross-protective immunity of live-attenuated chimeric PCV1-2b vaccine against PCV2b and PCV2d subtype challenge in pigs[J]. Frontiers in Microbiology, 2018, 9: 455.

[89] Cui X, Wang XB, Gao QQ, et al. Colonisation of mice and pigs by a chimeric porcine circovirus 1-2 prototype vaccine strain and a PCV2 isolate originating in China and their induction of cytokines[J]. Journal of Virological Methods, 2020, 283: 113905.

[90] Beach NM, Smith SM, 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]. Journal of Virology, 2011, 85(9): 4591-4595.

[91] Huang LP, Lu YH, Wei YW, et al. Construction and biological characterisation of recombinant porcine circovirus type 2 expressing the V5 epitope tag[J]. Virus Research, 2011, 161(2): 115-123.

[92] Rakibuzzaman A, Piñeyro P, Pillatzki A, et al. Harnessing the genetic plasticity of porcine circovirus type 2 to target suicidal replication[J]. Viruses, 2021, 13(9): 1676.

[93] Park KH, Oh T, Yang S, et al. Evaluation of a porcine circovirus type 2a (PCV2a) vaccine efficacy against experimental PCV2a, PCV2b, and PCV2d challenge[J]. Veterinary Microbiology, 2019, 231: 87-92.

[94] Opriessnig T, Karuppannan AK, Halbur PG, et al. Porcine circovirus type 2a or 2b based experimental vaccines provide protection against PCV2d/porcine parvovirus 2 co-challenge[J]. Vaccine, 2020, 38(8): 1975-1981.

[95] Kang SJ, Bae SM, Lee HJ, et al. Porcine circovirus (PCV) genotype 2d-based virus-like particles (VLPs) induced broad cross-neutralizing antibodies against diverse genotypes and provided protection in dual-challenge infection of a PCV2d virus and a type 1 porcine reproductive and respiratory syndrome virus (PRRSV)[J]. Pathogens, 2021, 10(9): 1145.

[96] Kim K, Hahn TW. Evaluation of novel recombinant porcine circovirus type 2d (PCV2d) vaccine in pigs naturally infected with PCV2d[J]. Vaccine, 2021, 39(3): 529-535.

[97] Ju L, Jayaramaiah U, Lee MA, et al. A field efficacy trial of recombinant porcine circovirus type 2d vaccine in three herds[J]. Vaccines, 2023, 11(9): 1497.

[98] Yu C, Cao MX, Wei YW, et al. Evaluation of cross-immunity among major porcine circovirus type 2 genotypes by infection with PCV2b and PCV2d circulating strains[J]. Veterinary Microbiology, 2023, 283: 109796.

[99] Kroeger M, Fano E, Sponheim A, et al. Assessment of homologous and heterologous PCV2 vaccine efficacy in a PCV2d/PRRSV co-challenge model[J]. Vaccine, 2025, 60: 127303.

[100] Venegas-Vargas C, Taylor LP, Foss DL, et al. Cellular and humoral immunity following vaccination with two different PCV2 vaccines (containing PCV2a or PCV2a/PCV2b) and challenge with virulent PCV2d[J]. Vaccine, 2021, 39(39): 5615-5625.

[101] Um H, Yang S, Oh T, et al. Comparative evaluation of growth performance between bivalent and trivalent vaccines containing porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae in a herd with subclinical PCV2d infection and enzootic pneumonia[J]. Vaccines, 2021, 9(5): 450.

[102] Pleguezuelos P, Sibila M, Ramírez C, et al. Efficacy studies against PCV-2 of a new trivalent vaccine including PCV-2a and PCV-2b genotypes and Mycoplasma hyopneumoniae when administered at 3 weeks of age[J]. Vaccines, 2022, 10(12): 2108.

[103] Wei YW, Zhu HZ, Huang LP, et al. Efficacy in pigs of a new inactivated vaccine combining porcine circovirus type 2 and Mycoplasma hyorhinis[J]. Veterinary Microbiology, 2020, 242: 108588.

[104] Chen JY, Wu CM, Chia MY, et al. A prospective CSFV-PCV2 bivalent vaccine effectively protects against classical swine fever virus and porcine circovirus type 2 dual challenge and prevents horizontal transmission[J]. Veterinary Research, 2023, 54(1): 57.

[105] Chen YS, Lee CY, Wu CC, et al. Efficacy evaluation of a bivalent subunit vaccine against classical swine fever virus and porcine circovirus type 2[J]. Scientific Reports, 2024, 14: 2997.

[106] Chen YC, Chung WB, Chaung HC, et al. Development of an effective single-dose PCV2/CSFV bivalent subunit vaccine against classical swine fever virus and porcine circovirus type 2[J]. Vaccines, 2025, 13(7): 736.

[107] Allen M, Roerink F, Crowley A, et al. Efficacy and safety of a tri-valent ready-to-use porcine circovirus type 2a, Mycoplasma hyopneumoniae and Lawsonia intracellularis vaccine in weaned pigs[J]. Vaccines, 2025, 13(7): 681.

[108] Yang S, Park SJ, Oh T, et al. Efficacy comparison of commercial porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae monovalent and bivalent vaccines against a dual challenge[J]. Revue Canadienne de Recherche Veterinaire, 2020, 84(4): 272-282.

[109] Cho H, Oh T, Suh J, et al. A comparative field evaluation of the effect of growth performance between porcine circovirus type 2a (PCV2a)-and PCV2b-based bivalent vaccines containing PCV2 and Mycoplasma hyopneumoniae[J]. Frontiers in Veterinary Science, 2022, 9: 859344.

[110] Pálmai N, Széplaki N, Molnár B, et al. Non-compromised efficacy of the first commercial ready-to-use genotype 2d porcine circovirus type 2 and Mycoplasma hyopneumoniae vaccine[J]. Viruses, 2025, 17(4): 554.

[111] 邱冬， 陈昌海， 闫喜军， 等. 高致病性猪繁殖与呼吸综合征活疫苗和猪圆环病毒 2 型灭活疫苗联合免疫效果的评价[J]. 畜牧与兽医， 2026， 58(2): 104-109.

[112] Qiu D, Chen CH, Yan XJ, et al. Evaluation on the combined immunization effect of live vaccine for highly pathogenic porcine reproductive and respiratory syndrome and inactivated vaccine for porcine circovirus type 2[J]. Animal Husbandry & Veterinary Medicine, 2026, 58(2): 104-109(in Chinese with English abstract).

[113] Puig A, Bernal I, Sabaté D, et al. Comparison of effects of a single dose of MHYOSPERE® PCVID with three commercial porcine vaccine associations against Mycoplasma hyopneumoniae (Mhyo) and porcine circovirus type 2 (PCV2) on piglet growth during the nursery period under field conditions[J]. Veterinary Research Communications, 2022, 46(4): 1167-1173.

[114] Suh J, Oh T, Chae C. An evaluation of intradermal all-in-one vaccine based on an inactivated recombinant Mycoplasma hyopneumoniae strain expressing porcine circovirus type 2 (PCV2) capsid protein against Korean stains of PCV2d and M. hyopneumoniae challenge[J]. Comparative Immunology, Microbiology and Infectious Diseases, 2022, 90: 101911.

[115] Hu GW, Wang ND, Yu WT, et al. Generation and immunogenicity of porcine circovirus type 2 chimeric virus-like particles displaying porcine reproductive and respiratory syndrome virus GP5 epitope B[J]. Vaccine, 2016, 34(16): 1896-1903.

[116] Li WL, Wang XW, Bai J, et al. Construction and immunogenicity of recombinant porcine circovirus-like particles displaying somatostatin[J]. Veterinary Microbiology, 2013, 163(1/2): 23-32.

[117] Zhang HW, Qian P, Liu LF, et al. Virus-like particles of chimeric recombinant porcine circovirus type 2 as antigen vehicle carrying foreign epitopes[J]. Viruses, 2014, 6(12): 4839-4855.

[118] Jung BK, Kim HR, Jang H, et al. Replacing the decoy epitope of PCV2 capsid protein with epitopes of GP3 and/or GP5 of PRRSV enhances the immunogenicity of bivalent vaccines in mice[J]. Journal of Virological Methods, 2020, 284: 113928.

[119] Liu ZH, Deng ZF, Lu Y, et al. A modular and self-adjuvanted multivalent vaccine platform based on porcine circovirus virus-like nanoparticles[J]. Journal of Nanobiotechnology, 2022, 20(1): 493.

[120] Chen YL, Zhu JH, Wang SQ, et al. Modular nano-antigen display platform for pigs induces potent immune responses[J]. ACS Nano, 2024, 18(42): 29152-29177.

[121] Opriessnig T, Karuppannan AK, Castro AMMG, et al. Porcine circoviruses: current status, knowledge gaps and challenges[J]. Virus Research, 2020, 286: 198044.

[122] Rakibuzzaman A, Ramamoorthy S. Comparative immunopathogenesis and biology of recently discovered porcine circoviruses[J]. Transboundary and Emerging Diseases, 2021, 68(6): 2957-2968.

[123] Wu X, Wang Q, Lu W, et al. The PCV3 cap virus-like particle vaccine with the chimeric PCV2-neutralizing epitope gene is effective in mice[J]. Veterinary Sciences, 2024, 11(6): 264.

基金资助

国家现代农业产业技术体系专项(CARS-34)

江苏省农业科技自主创新资金项目(CX(22)1011)

中央高校基本业务费基础研究项目(PY2026009)