The PCV3 Cap Virus-like Particle Vaccine with the Chimeric PCV2-Neutralizing Epitope Gene Is Effective in Mice

Overview

Journal Vet Sci

Publisher MDPI

Specialty Veterinary Medicine

Date 2024 Jun 26

PMID 38922011

Authors

Xingchen Wu

Qikai Wang

Wang Lu

Ying Wang

Zehao Han

Libin Liang

Shimin Gao

Haili Ma

XiaoMao Luo

Affiliations

Soon will be listed here.

Abstract

Porcine circovirus type 3 (PCV3) infection can cause symptoms similar to those of porcine circovirus type 2 (PCV2) infection, and coinfections with both PCV2 and PCV3 are observed in the swine industry. Consequently, developing chimeric vaccines is essential to prevent and control porcine circovirus infections. In this study, we used both and mammalian expression systems to express PCV3 Cap (Cap3) and a chimeric gene containing the PCV2-neutralizing epitope within the PCV3 Cap (Cap3-Cap2E), which were assembled into virus-like particle (VLP) vaccines. We found that Cap3 lacking nuclear localization signal (NLS) could not form VLPs, while Cap3 with a His-tag successfully assembled into VLPs. Additionally, the chimeric of PCV2-neutralizing epitopes did not interfere with the assembly process of VLPs. Various immunization approaches revealed that pCap3-Cap2E VLP vaccines were capable of activating high PCV3 Cap-specific antibody levels and effectively neutralizing both PCV3 and PCV2. Furthermore, pCap3-Cap2E VLPs demonstrated a potent ability to activate cellular immunity, protecting against PCV3 infection and preventing lung damage in mice. In conclusion, this study successfully developed a PCV3 Cap VLP vaccine incorporating chimeric PCV2-neutralizing epitope genes, providing new perspectives for PCV3 vaccine development.

References

Lua L, Connors N, Sainsbury F, Chuan Y, Wibowo N, Middelberg A . Bioengineering virus-like particles as vaccines. Biotechnol Bioeng. 2013; 111(3):425-40. DOI: 10.1002/bit.25159. View

Vemula S, Sayedahmed E, Sambhara S, Mittal S . Vaccine approaches conferring cross-protection against influenza viruses. Expert Rev Vaccines. 2017; 16(11):1141-1154. PMC: 6005355. DOI: 10.1080/14760584.2017.1379396. View

Yu W, Sun Y, He Q, Sun C, Dong T, Zhang L . Mitochondrial Localization Signal of Porcine Circovirus Type 2 Capsid Protein Plays a Critical Role in Cap-Induced Apoptosis. Vet Sci. 2021; 8(11). PMC: 8624748. DOI: 10.3390/vetsci8110272. View

Qi S, Su M, Guo D, Li C, Wei S, Feng L . Molecular detection and phylogenetic analysis of porcine circovirus type 3 in 21 Provinces of China during 2015-2017. Transbound Emerg Dis. 2019; 66(2):1004-1015. DOI: 10.1111/tbed.13125. View

Kedkovid R, Woonwong Y, Arunorat J, Sirisereewan C, Sangpratum N, Kesdangsakonwut S . Porcine circovirus type 3 (PCV3) shedding in sow colostrum. Vet Microbiol. 2018; 220:12-17. DOI: 10.1016/j.vetmic.2018.04.032. View

Fontana D, Kratje R, Etcheverrigaray M, Prieto C . Rabies virus-like particles expressed in HEK293 cells. Vaccine. 2014; 32(24):2799-804. DOI: 10.1016/j.vaccine.2014.02.031. View

Rani N, Kapoor N, Krishnan A . Efficient generation and characterization of chimeric dengue viral-like particles. Biochem Biophys Res Commun. 2023; 654:10-17. DOI: 10.1016/j.bbrc.2023.02.052. View

Bera B, Choudhary M, Anand T, Virmani N, Sundaram K, Choudhary B . Detection and genetic characterization of porcine circovirus 3 (PCV3) in pigs in India. Transbound Emerg Dis. 2019; 67(3):1062-1067. DOI: 10.1111/tbed.13463. View

Chen Y, Liu Y, Zhang G, Wang A, Dong Z, Qi Y . Human papillomavirus L1 protein expressed in Escherichia coli self-assembles into virus-like particles that are highly immunogenic. Virus Res. 2016; 220:97-103. DOI: 10.1016/j.virusres.2016.04.017. View

10.

Kim S, Park J, Jung J, Kim H, Park Y, Lee K . Detection and genetic characterization of porcine circovirus 3 from aborted fetuses and pigs with respiratory disease in Korea. J Vet Sci. 2018; 19(5):721-724. PMC: 6167340. DOI: 10.4142/jvs.2018.19.5.721. View

11.

Imagawa T, Ito M, Matsuda M, Nakashima K, Tokunaga Y, Ohta I . Virus-like particles with FLAG-tagged envelope protein as a tetravalent dengue vaccine candidate. Sci Rep. 2021; 11(1):17542. PMC: 8413300. DOI: 10.1038/s41598-021-97038-4. View

12.

Palinski R, Pineyro P, Shang P, Yuan F, Guo R, Fang Y . A Novel Porcine Circovirus Distantly Related to Known Circoviruses Is Associated with Porcine Dermatitis and Nephropathy Syndrome and Reproductive Failure. J Virol. 2016; 91(1). PMC: 5165205. DOI: 10.1128/JVI.01879-16. View

13.

Ninyio N, Ho K, Omar A, Tan W, Iqbal M, Mariatulqabtiah A . Virus-like Particle Vaccines: A Prospective Panacea Against an Avian Influenza Panzootic. Vaccines (Basel). 2020; 8(4). PMC: 7712863. DOI: 10.3390/vaccines8040694. View

14.

Chackerian B, Durfee M, Schiller J . Virus-like display of a neo-self antigen reverses B cell anergy in a B cell receptor transgenic mouse model. J Immunol. 2008; 180(9):5816-25. PMC: 3493123. DOI: 10.4049/jimmunol.180.9.5816. View

15.

Park J, Kim J, Park J, Jun S, Shin H . A chimeric MERS-CoV virus-like particle vaccine protects mice against MERS-CoV challenge. Virol J. 2022; 19(1):112. PMC: 9235161. DOI: 10.1186/s12985-022-01844-9. View

16.

Cao X, Huang M, Wang Y, Chen Y, Yang H, Quan F . Immunogenicity Analysis of PCV3 Recombinant Capsid Protein Virus-like Particles and Their Application in Antibodies Detection. Int J Mol Sci. 2023; 24(12). PMC: 10299735. DOI: 10.3390/ijms241210377. View

17.

Beach N, Ramamoorthy S, Opriessnig T, Wu S, Meng X . 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.... Vaccine. 2010; 29(2):221-32. DOI: 10.1016/j.vaccine.2010.10.050. View

18.

Frietze K, Peabody D, Chackerian B . Engineering virus-like particles as vaccine platforms. Curr Opin Virol. 2016; 18:44-9. PMC: 4983494. DOI: 10.1016/j.coviro.2016.03.001. View

19.

Mengfan Q, Xifeng W, Guowu Z, Qingling M, Jun Q, Lixia W . Molecular Detection and Genetic Diversity of Type 3 in Commercial Pig Farms in Xinjiang Province, China. J Vet Res. 2020; 63(4):481-488. PMC: 6950430. DOI: 10.2478/jvetres-2019-0071. View

20.

Vargas-Bermudez D, Mogollon J, Jaime J . The Prevalence and Genetic Diversity of PCV3 and PCV2 in Colombia and PCV4 Survey during 2015-2016 and 2018-2019. Pathogens. 2022; 11(6). PMC: 9228467. DOI: 10.3390/pathogens11060633. View