A Subunit Vaccine Harboring the Fusion Capsid Proteins of Porcine Circovirus Types 2, 3, and 4 Induces Protective Immune Responses in a Mouse Model

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2025 Jan 8

PMID 39772270

Authors

Qikai Wang

Ran Zhang

Yue Wang

Ying Wang

Libin Liang

Haili Ma

Haidong Wang

Longlong Si

Xingchen Wu

Affiliations

Soon will be listed here.

Abstract

Coinfections with porcine circovirus types 2, 3, and 4 (PCV2, PCV3, and PCV4) are increasingly being detected in the swine industry. However, there is no commercially available vaccine which prevents coinfection with PCV2, PCV3, and PCV4. The development of a vaccine expressing capsid (Cap) fusion proteins of multiple PCVs represents a promising approach for broadly preventing infection with PCVs. In this study, we developed a PCV subunit vaccine candidate (Cap 2-3-4) by predicting, screening, and fusing antigenic epitopes of Cap proteins of PCV2, PCV3, and PCV4. Immunoprotection assays showed that the prokaryotic expression of Cap 2-3-4 could effectively induce high levels of PCV2, PCV3, and PCV4 Cap-specific antibodies and successfully neutralize both PCV2 and PCV3. Furthermore, Cap 2-3-4 demonstrated a potent ability to activate cellular immunity and thus prevent lung damage in mice. This study provides a new option for the development of broad vaccines against PCVs.

References

Chen X, Zhao Y, Liu X, Han Y, Zhang Y, Hou C . Molecular detection and genetic characteristics of a novel porcine circovirus (porcine circovirus 4) and porcine reproductive and respiratory syndrome virus in Shaanxi and Henan Provinces of China. Comp Immunol Microbiol Infect Dis. 2023; 98:102009. DOI: 10.1016/j.cimid.2023.102009. View

Dei Giudici S, Mura L, Bonelli P, Hawko S, Angioi P, Sechi A . Evidence of Porcine Circovirus Type 2 (PCV2) Genetic Shift from PCV2b to PCV2d Genotype in Sardinia, Italy. Viruses. 2023; 15(11). PMC: 10674684. DOI: 10.3390/v15112157. View

Kroeger M, Vargas-Bermudez D, Jaime J, Parada J, Groeltz J, Gauger P . First detection of PCV4 in swine in the United States: codetection with PCV2 and PCV3 and direct detection within tissues. Sci Rep. 2024; 14(1):15535. PMC: 11226432. DOI: 10.1038/s41598-024-66328-y. View

Rcheulishvili N, Mao J, Papukashvili D, Feng S, Liu C, Yang X . Development of a Multi-Epitope Universal mRNA Vaccine Candidate for Monkeypox, Smallpox, and Vaccinia Viruses: Design and In Silico Analyses. Viruses. 2023; 15(5). PMC: 10222975. DOI: 10.3390/v15051120. View

Yang X, Ma T, Ouyang H, Chen F, Peng Z, Li C . Effect of atovastatin treatment on porcine circovirus 2 infection in BALB/c mice. Clin Exp Pharmacol Physiol. 2015; 42(8):817-21. DOI: 10.1111/1440-1681.12434. View

Porowinska D, Wujak M, Roszek K, Komoszynski M . [Prokaryotic expression systems]. Postepy Hig Med Dosw (Online). 2013; 67:119-29. DOI: 10.5604/17322693.1038351. View

Meng X . Porcine circovirus type 2 (PCV2): pathogenesis and interaction with the immune system. Annu Rev Anim Biosci. 2014; 1:43-64. DOI: 10.1146/annurev-animal-031412-103720. View

Hitchman R, Locanto E, Possee R, King L . Optimizing the baculovirus expression vector system. Methods. 2011; 55(1):52-7. DOI: 10.1016/j.ymeth.2011.06.011. View

Chavda V, Ghali E, Balar P, Chauhan S, Tiwari N, Shukla S . Protein subunit vaccines: Promising frontiers against COVID-19. J Control Release. 2024; 366:761-782. DOI: 10.1016/j.jconrel.2024.01.017. View

10.

Chen N, Huang Y, Ye M, Li S, Xiao Y, Cui B . Co-infection status of classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circoviruses (PCV2 and PCV3) in eight regions of China from 2016 to 2018. Infect Genet Evol. 2018; 68:127-135. DOI: 10.1016/j.meegid.2018.12.011. View

11.

Kiupel M, Stevenson G, Galbreath E, North A, HogenEsch H, Mittal S . Porcine circovirus type 2 (PCV2) causes apoptosis in experimentally inoculated BALB/c mice. BMC Vet Res. 2005; 1:7. PMC: 1291377. DOI: 10.1186/1746-6148-1-7. View

12.

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

13.

Ji W, Zhang X, Niu G, Chen S, Li X, Yang L . Expression and immunogenicity analysis of the capsid proteins of porcine circovirus types 2 to 4. Int J Biol Macromol. 2022; 218:828-838. DOI: 10.1016/j.ijbiomac.2022.07.204. View

14.

Lv Q, Guo K, Zhang Y . Current understanding of genomic DNA of porcine circovirus type 2. Virus Genes. 2014; 49(1):1-10. DOI: 10.1007/s11262-014-1099-z. View

15.

Li H, Chen X, Zhao Y, Zhang H, Zheng L, Wang L . Simultaneous detection and phylogenetic analysis of porcine epidemic diarrhea virus and porcine circovirus 4 in Henan province, China. Arch Virol. 2023; 168(6):161. DOI: 10.1007/s00705-023-05791-w. View

16.

Ha Z, Yu C, Xie C, Wang G, Zhang Y, Hao P . Retrospective surveillance of porcine circovirus 4 in pigs in Inner Mongolia, China, from 2016 to 2018. Arch Virol. 2021; 166(7):1951-1959. DOI: 10.1007/s00705-021-05088-w. View

17.

Li T, Qian C, Gu Y, Zhang J, Li S, Xia N . Current progress in the development of prophylactic and therapeutic vaccines. Sci China Life Sci. 2022; 66(4):679-710. PMC: 9734355. DOI: 10.1007/s11427-022-2230-4. View

18.

Ouyang T, Zhang X, Liu X, Ren L . Co-Infection of Swine with Porcine Circovirus Type 2 and Other Swine Viruses. Viruses. 2019; 11(2). PMC: 6410029. DOI: 10.3390/v11020185. View

19.

Liu C, Liu Y, Feng H, Zhao B, Chen Y, Huang H . PCV cap proteins fused with calreticulin expressed into polymers in Escherichia coli with high immunogenicity in mice. BMC Vet Res. 2020; 16(1):313. PMC: 7450944. DOI: 10.1186/s12917-020-02527-9. View

20.

Masuda A, Lee J, Miyata T, Sato T, Hayashi S, Hino M . Purification and characterization of immunogenic recombinant virus-like particles of porcine circovirus type 2 expressed in silkworm pupae. J Gen Virol. 2018; 99(7):917-926. DOI: 10.1099/jgv.0.001087. View