Recombinant Flagellin-Porcine Circovirus Type 2 Cap Fusion Protein Promotes Protective Immune Responses in Mice

Porcine circovirus Type 2 (PCV2) is a primary etiological pathogen of post-weaning multi-systemic wasting syndrome (PMWS). The capsid protein of PCV2 is the crucial immunogenic protein which can induce antibody generation and immune responses. However, there is still a lack of efficient PCV2 vaccines with high immunogenicity. In the current study, we developed a novel engineered PCV2 capsid (∆1-41aa)-pFc fusion protein (PCFP), which comprised a truncated capsid protein of PCV2 and a porcine IgG Fc fragment, fused to the capsid protein of PCV2 at the C-terminus. We found that this novel fusion protein could auto-assemble into virus-like nanoparticles with an estimated mean diameter of 22.6 nm, characterized by transmission electron microscopy. Immunization of BALB/c mice with this fusion protein significantly increased the production levels of anti-PCV2-capsid protein antibody in serum. Besides, the virus-like nanoparticles, PCFP was demonstrated to induce efficient cellular immune responses in mice, as evident by the high specific T cell reactivity to the PCFP fusion protein and the high production of the immune cytokines IFN-γ and IL-10 in an ex vivo re-stimulation system. Collectively, these findings demonstrate that the PCV2 truncated capsid subunit Fc-fusion protein can induce both cellular and humoral immune responses, and it displays great application potential.

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Immune Responses of Piglets Immunized by a Recombinant Plasmid Containing Porcine Circovirus Type 2 and Porcine Interleukin-18 Genes

Viral Immunology ◽

10.1089/vim.2014.0036 ◽

2014 ◽

Vol 27 (10) ◽

pp. 521-528 ◽

Cited By ~ 3

Author(s):

Guang-Lei Chen ◽

Peng-Fei Fu ◽

Lin-Qing Wang ◽

Xin-Sheng Li ◽

Hong-Ying Chen

Keyword(s):

Immune Responses ◽

Recombinant Plasmid ◽

Porcine Circovirus Type ◽

Porcine Circovirus Type 2 ◽

Porcine Circovirus ◽

Interleukin 18

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Host immune response to infection with porcine circoviruses

Animal Diseases ◽

10.1186/s44149-021-00027-3 ◽

2021 ◽

Vol 1 (1) ◽

Author(s):

Ruihan Shi ◽

Lei Hou ◽

Jue Liu

Keyword(s):

Immune Response ◽

Immune Responses ◽

Inflammatory Responses ◽

Porcine Circovirus Type ◽

Porcine Circovirus Type 2 ◽

Immune Defense ◽

Porcine Circovirus ◽

Future Research ◽

Host Immune System

AbstractPorcine circovirus type 2 (PCV2), which serves as a major causative agent of PCV2-associated diseases and causes severe loss to the pig industry worldwide, can dysregulate the immune response and induce immunosuppression in PCV2-infected pigs. Similar to PCV2, porcine circovirus type 3 (PCV3), a newly identified swine circovirus which might be closely associated with porcine dermatitis and nephropathy syndrome, reproductive disorder, and multisystemic inflammatory responses, also interferes with host immune defense. Interaction between host immune system and PCVs is considered to be a crucial determinant of pathogenicity in pigs. Here, we sought to briefly discuss the current knowledge regarding the interaction of porcine circovirus type 2 and/or 3 with host immune cells and immune responses to better depict the viral immunomodulatory capacity, pathogenic mechanisms, and the future research direction in host immune responses to infection with PCV2 and PCV3.

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Immune responses induced by a combined vaccination with a recombinant chimera of Mycoplasma hyopneumoniae antigens and capsid virus-like particles of porcine circovirus type 2

BMC Veterinary Research ◽

10.1186/s12917-020-02560-8 ◽

2020 ◽

Vol 16 (1) ◽

Author(s):

Yu Tao ◽

Rui Yang ◽

Jianhong Shu ◽

Wenqian Zheng ◽

Jian Chen ◽

...

Keyword(s):

Immune Responses ◽

Mycoplasma Hyopneumoniae ◽

Porcine Circovirus Type ◽

Porcine Circovirus Type 2 ◽

Negative Control ◽

Porcine Circovirus ◽

Protein Antigens ◽

Virus Like Particles ◽

Antibody Levels

Abstract Background Mycoplasma hyopneumoniae (Mhp) and porcine circovirus type 2 (PCV2) are two important pathogens causing Mycoplasma pneumonia of swine (MPS) and porcine circovirus diseases and porcine circovirus-associated diseases (PCVDs/PCVADs), respectively, and resulted in considerable economic loss to the swine industry worldwide. Currently, vaccination is one of the main measures to control these two diseases; however, there are few combination vaccines that can prevent these two diseases. To determine the effect of combination immunization, we developed capsid-derived (Cap) virus-like particles (VLPs) of PCV2 and a new recombinant chimera composed of the P97R1, P46, and P42 antigens of Mhp. Then we investigated the immune responses induced by the immunization with this combination vaccine in mice and piglets. Results The high level antibodies against three protein antigens (P97R1, P46, and P42 of Mhp) were produced after immunization, up to or higher than 1:400,000; the antibody levels in Pro group continuously increased throughout the 42 days for all the antigens tested. The lymphocyte proliferative response in PCV2 group was stronger than that in PBS, VP, Mhp CV in mice. The antibody levels for Cap remained stable and reached the peak at 35 DAI. The IFN-γ and IL-4 in sera were significantly enhanced in the Pro group than that in the negative control-VP group on Day 14 and 28 post-the first immunization in piglets. Conclusions Above all, the combination immunization could induce humoral and cellular immune responses against all four antigens in mice and piglets. Therefore, our approach is a simple and effective vaccination strategy to protect pigs against MPS and PCVD/PCVAD.

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Immunity Elicited by an Experimental Vaccine Based on Recombinant Flagellin-Porcine Circovirus Type 2 Cap Fusion Protein in Piglets

PLoS ONE ◽

10.1371/journal.pone.0147432 ◽

2016 ◽

Vol 11 (2) ◽

pp. e0147432 ◽

Cited By ~ 10

Author(s):

Shanshan Zhu ◽

Chunyan Zhang ◽

Jing Wang ◽

Li Wei ◽

Rong Quan ◽

...

Keyword(s):

Fusion Protein ◽

Porcine Circovirus Type ◽

Porcine Circovirus Type 2 ◽

Porcine Circovirus

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156. Protective Immune Responses Against Porcine Circovirus Type 2 Infection Generated by a Recombinant Modified Vaccinia Virus Expressing the Viral ORF Antigens as Vaccines

Molecular Therapy ◽

10.1016/s1525-0016(16)44362-5 ◽

2007 ◽

Vol 15 ◽

pp. S60

Keyword(s):

Immune Responses ◽

Vaccinia Virus ◽

Porcine Circovirus Type ◽

Porcine Circovirus Type 2 ◽

Porcine Circovirus

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Swine Influenza Virus Infection Decreases the Protective Immune Responses of Subunit Vaccine Against Porcine Circovirus Type 2

Frontiers in Microbiology ◽

10.3389/fmicb.2021.807458 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuhang Sun ◽

Jinlong Zhang ◽

Zixuan Liu ◽

Ying Zhang ◽

Kehe Huang

Keyword(s):

Influenza Virus ◽

Immune Responses ◽

Subunit Vaccine ◽

Swine Influenza Virus ◽

Swine Influenza ◽

Porcine Circovirus Type ◽

Porcine Circovirus Type 2 ◽

Porcine Circovirus ◽

Siv Infection

Porcine circovirus type 2 (PCV2) is the primary pathogen of porcine circovirus diseases and porcine circovirus associated diseases. Immunization with a vaccine is considered an effective measure to control these diseases. However, it is still unknown whether PCV2 vaccines have protective immune responses on the animals infected with swine influenza virus (SIV), a pandemic virus in swine herds. In this study, we first compared the effects of 2 different PCV2 vaccines on normal mice and SIV-infected mice, respectively. The results showed that these two vaccines had protective immune responses in normal mice, and the subunit vaccine (vaccine S) had better effects. However, the inactivated vaccine (vaccine I) instead of vaccine S exhibited more immune responses in the SIV-infected mice. SIV infection significantly decreased the immune responses of vaccine S in varying aspects including decreased PCV2 antibody levels and increased PCV2 replication. Mechanistically, further studies showed that SIV infection increased IL-10 expression and M2 macrophage percentage, but decreased TNF-α expression and M1 macrophage percentage in the mice immunized with vaccine S; on the contrary, macrophage depleting by using clodronate-containing liposomes significantly alleviated the SIV infection-induced decrease in the protective immune responses of vaccine S against PCV2. This study indicates that SIV infection decreases the protective immune responses of vaccine S against PCV2. The macrophage polarization induced by SIV infection might facilitate decreased immune responses to vaccine S, which provides new insight into vaccine evaluation and a reference for the analysis of immunization failure.

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