Chimeric hepatitis B virus core particles displaying Neisserial surface protein A confer protection against virulent Neisseria meningitidis serogroup B in BALB/c mice

YongLi Hou,1 Ting Yan,2 Hui Cao,1 Peng Liu,1 Kang Zheng,1 Zhenyu Li,1 Qing Deng,1 SiHai Hu11Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Institution of Pathogenic Biology, Hengyang Medical College, University of South China, Hengyang 421001, People’s Republic of China; 2Department of Health Services, Air Force Medical University, Xi’an, Shaanxi 710032, People’s Republic of ChinaCorrespondence: SiHai HuInstitution of Pathogenic Biology, Hengyang Medical College, University of South China, 28 West Changsheng Road, Hengyang 421001, Hunan, People’s Republic of ChinaTel +86 1 397 340 7567Fax +86 734 828 2907Email hhsshh_518@163.comPurpose: The primary goal of the present study was to explore and evaluate the highly conserved Neisserial surface protein A (NspA) molecule, fused with truncated HBV virus-like particles (VLPs), as a candidate vaccine against the virulent Neisseria meningitidis serogroup B (NMB).Methods: NspA was inserted into the major immunodominant region of the truncated hepatitis B virus core protein (HBc; amino acids 1–144). The chimeric protein, HBc-N144-NspA, was expressed from a prokaryotic vector and generated HBc-like particles, as determined by transmission electron microscopy. Further, the chimeric protein and control proteins were used to immunize mice and the resulting immune responses evaluated by flow cytometry, enzyme-linked immunosorbent assay, and analysis of serum bactericidal activity (SBA) titer.Results: Evaluation of the immunogenicity of the recombinant HBc-N144-NspA protein showed that it elicited the production of high levels of NspA-specific total IgG. The SBA titer of HBc-N144-NspA/F reached 1:16 2 weeks after the last immunization in BALB/c mice, when human serum complement was included in the vaccine. Immunization of HBc-N144-NspA, even without adjuvant, induced high levels of IL-4 and a high IgG1 to IgG2a ratio, confirming induction of an intense Th2 immune response. Levels of IL-17A increased rapidly in mice after the first immunization with HBc-N144-NspA, indicating the potential for this vaccine to induce a mucosal immune response. Meanwhile, the immunization of HBc-N144-NspA without adjuvant induced only mild inflammatory infiltration into the mouse muscle tissue.Conclusion: This study demonstrates that modification using HBc renders NspA a candidate vaccine, which can trigger protective immunity against NMB.Keywords: hepatitis B core protein, Neisserial surface protein A, virus-like particles, recombinant protein vaccine, Neisseria meningitidis serogroup B