Abstract

Chimeric virus-like particles (VLPs) have been widely exploited for various purposes including their use as vaccine candidates, particularly due to their ability to induce stronger immune responses than VLPs consisting of single viral proteins. In the present study, VLPs of the Macrobrachium rosenbergii nodavirus (MrNV) capsid protein (Nc) displaying the hepatitis B virus “a” determinant (aD) were produced in Spodoptera frugiperda (Sf9) insect cells. BALB/c mice immunised with the purified chimeric Nc-aD VLPs elicited a sustained titre of anti-aD antibody, which was significantly higher than that elicited by a commercially available hepatitis B vaccine and Escherichia coli-produced Nc-aD VLPs. Immunophenotyping showed that the Sf9-produced Nc-aD VLPs induced proliferation of cytotoxic T-lymphocytes and NK1.1 natural killer cells. Furthermore, enzyme-linked immunospot (ELISPOT)analysis showed the presence of antibody-secreting memory B cells in the mice splenocytes stimulated with the synthetic aD peptide. The significant humoral, natural killer cell and memory B cell immune responses induced by the Sf9-produced Nc-aD VLPs suggest that they present good prospects for use as a hepatitis B vaccine candidate.

Highlights

  • Hepatitis B has been declared by the World Health Organization (WHO) as one of the major health concerns of the century

  • nodavirus (MrNV) capsid protein (Nc)-a” determinant (aD) virus-like particles (VLPs) were purified by IMAC from the culture supernatant and cell lysate of the Sf9 cells infected with 10% of the P1 baculovirus stock

  • Transmission electron microscopic analysis revealed that the Nc-aD produced in Sf9 assembled into spherical VLPs of different sizes, ranging from ~21 nm to ~55 nm, while the E. coli-produced Nc-aD protein assembled into VLPs of ~30 nm in diameter (Figure 2)

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Summary

Introduction

Hepatitis B has been declared by the World Health Organization (WHO) as one of the major health concerns of the century. The disease is caused by hepatitis B virus (HBV), which belongs to the family Hepadnaviridae [1,2]. About 250 million people, globally, are living carriers of HBV, and yearly recorded deaths due to hepatitis B are estimated about 1 million [3]. None of the available treatment regimens against hepatitis B is curative, and concerns have been raised with regards to the efficacies of the available vaccines. Some limitations of the available hepatitis B vaccines include their inability to elicit sustained protective immunity in some individuals [4,5], their ineffectiveness in Vaccines 2020, 8, 275; doi:10.3390/vaccines8020275 www.mdpi.com/journal/vaccines. Continuous development of more effective hepatitis B vaccines is essential

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