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

Abstract

Purpose 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.

Heterologous expression of Chimeric hepatitis B core virus like particles harboring SARS-CoV2 epitope and evaluation of its immunization potential in mice

“…According to the results, the adjuvant positively affected the immune response in terms of IgG antibodies. Consistent with these results, Hou et al (2019) reported that the maximum antibody titer was produced when the HBc-fused antigen was injected with Freund's adjuvant. In spite of the self-adjuvant property of the VLP vaccine, the utilization of proper adjuvant can strongly elevate the e cient immune response [15,39,40].…”

“…Consistent with these results, Hou et al (2019) reported that the maximum antibody titer was produced when the HBc-fused antigen was injected with Freund's adjuvant. In spite of the self-adjuvant property of the VLP vaccine, the utilization of proper adjuvant can strongly elevate the e cient immune response [15,39,40]. Although Freund's adjuvant might not be safe for humans, because it is reported to be more highly immunogenic than other adjuvants in mice [41,42], we preferably used this adjuvant to examine the general response of HBc-E VLP in the presence to a potent adjuvant in comparison with immunized mice that were solely injected by HBc-E VLP.…”

“…Primarily serving as a molecular scaffold for exposing incorporated antigens, antigenic epitope sequences can be inserted into VLPs by genetic fusion. Different chimeric VLP-based vaccines against animal and human infectious diseases are investigated in the last few years [13,14,15,16,17]. In spite of their potential, a few studies have been carried out regarding the production of a VLP-based vaccine for SARS-CoV-2 infection.…”

Chimeric Hepatitis B core virus-like particles harboring SARS-CoV2 epitope elicit a humoral immune response in mice

“…According to the results, the adjuvant positively affected the immune response in terms of IgG antibodies at four weeks. Consistent with these results, [ 13 ] reported that the maximum antibody titer was produced when the HBc-fused antigen was injected with Freund’s adjuvant. In spite of the self-adjuvant property of the VLP vaccine, the utilization of proper adjuvant can strongly elevate the efficient immune response [ 13 , 39 , 40 ].…”

Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion

“…Their 180 subunits are structured in icosahedral T3 geometry with a diameter ranging from 25-30nm [36][37][38][39][40][41][42]. The last VLP tested was the hepatitis B virus protein capsid HBcAg which with 34 nm of diameter and 240 subunits was the largest VLP tested [22,[43][44][45]. Recently, the successful use of HBcAg as a scaffold for the display through genetic fusion of two meningococcal antigens (fHbp and NadA) has been reported.…”