Nanovaccine Confers Dual Protection Against Influenza A Virus And Porcine Circovirus Type 2

Abstract

Peiyang Ding,1,2,* Qianyue Jin,1,3,* Xinxin Chen,1 Suzhen Yang,1 Junqing Guo,1 Guangxu Xing,1 Ruiguang Deng,1 Aiping Wang,4 Gaiping Zhang1–4 1Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, People’s Republic of China; 2College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, People’s Republic of China; 3School of Life Sciences, Zhengzhou University, Zhengzhou 450001, People’s Republic of China; 4Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Aiping WangSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]  Gaiping ZhangCollege of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: The influenza A virus (IAV) is known for its high variability and poses a huge threat to the health of humans and animals. Pigs play a central role in the cross-species reassortment of IAV. Ectodomain of matrix protein 2 (M2e) is the most conserved protective antigen in IAV and can be used to develop nanovaccines through nanoparticles displaying to increase its immunogenicity. However, the high immunogenicity of nanoparticles can cause the risk of off-target immune response, and excess unwanted antibodies may interfere with the protective efficacy of M2e-specific antibodies. Therefore, it is necessary to select reasonable nanoparticles to make full use of antibodies against nanoparticles while increasing the level of M2e-specific antibodies. Porcine circovirus type 2 (PCV2) is the most susceptible virus in pigs and can promote IAV infection. It is meaningful to develop a vaccine that can simultaneously control swine influenza virus (SIV) and PCV2.Methods: In the present study, M2e of different copy numbers were inserted into the capsid (Cap) protein of PCV2 and expressed in Escherichia coli to form self-assembled chimeric virus-like particles (VLPs) nanovaccine. BALB/c mice and pigs were immunized with these nanovaccines to explore optimal anti-IAV and anti-PCV2 immunity.Results: Cap is capable of carrying at least 81 amino acid residues (three copies of M2e) at its C-terminal without impairing VLPs formation. Cap-3M2e VLPs induced the highest levels of M2e-specific immune responses, conferring protection against lethal challenge of IAVs from different species and induced specific immune responses consistent with PCV2 commercial vaccines in mice. In addition, Cap-3M2e VLPs induced high levels of M2e-specific antibodies and PCV2-specific neutralizing antibodies in pigs.Conclusion: Cap-3M2e VLP is an economical and promising bivalent nanovaccine, which provides dual protection against IAV and PCV2.Keywords: influenza A virus, porcine circovirus type 2, M2e, nanovaccine, virus-like particles, bivalent vaccine

Keywords

• Influenza A virus
• Porcine circovirus type 2
• M2e
• Nanovaccine
• Virus-like particles
• Bivalent vaccine