Hepatitis C Virus E1 and E2 Proteins Used as Separate Immunogens Induce Neutralizing Antibodies with Additive Properties.

Elodie Beaumont,Emmanuelle Roch,Philippe Roingeard,Lucie Chopin,Ranjit Ray

doi:10.1371/journal.pone.0151626

Elodie Beaumont, Emmanuelle Roch + Show 3 more

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https://doi.org/10.1371/journal.pone.0151626

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Abstract

Various strategies involving the use of hepatitis C virus (HCV) E1 and E2 envelope glycoproteins as immunogens have been developed for prophylactic vaccination against HCV. However, the ideal mode of processing and presenting these immunogens for effective vaccination has yet to be determined. We used our recently described vaccine candidate based on full-length HCV E1 or E2 glycoproteins fused to the heterologous hepatitis B virus S envelope protein to compare the use of the E1 and E2 proteins as separate immunogens with their use as the E1E2 heterodimer, in terms of immunogenetic potential and the capacity to induce neutralizing antibodies. The specific anti-E1 and anti-E2 antibody responses induced in animals immunized with vaccine particles harboring the heterodimer were profoundly impaired with respect to those in animals immunized with particles harboring E1 and E2 separately. Moreover, the anti-E1 and anti-E2 antibodies had additive neutralizing properties that increase the cross-neutralization of heterologous strains of various HCV genotypes, highlighting the importance of including both E1 and E2 in the vaccine for an effective vaccination strategy. Our study has important implications for the optimization of HCV vaccination strategies based on HCV envelope proteins, regardless of the platform used to present these proteins to the immune system.

Highlights

Hepatitis C virus (HCV) infection, which affects an estimated 170 million people worldwide and frequently leads to severe chronic liver disease, constitutes a major global health concern [1]
With biological material collected during a previous study [25], the separate contributions of the E1 and E2 envelope glycoproteins to the humoral immune responses induced in rabbits immunized with chimeric particles bearing E1, E2 or the heterodimer E1E2
These results suggest that the immunogenicity of the two HCV envelope glycoproteins presented at the surface of the chimeric particles as a heterodimer was much weaker than that of the two envelope proteins exposed individually

Summary

Introduction

Hepatitis C virus (HCV) infection, which affects an estimated 170 million people worldwide and frequently leads to severe chronic liver disease, constitutes a major global health concern [1]. The recent introduction of direct-acting antiviral agents has considerably improved the treatment of chronic HCV infection [2], but the eradication of this viral disease is hampered by most HCV-infected subjects being unaware of their infection status and the very high cost of the new treatment, which is unaffordable in lower-income countries [3]. It has been estimated that the world reservoir of HCV-infected individuals increases by three to four million newly infected subjects each year, and that this phenomenon is not limited to developing countries, as 18,000 new HCV infections are thought to occur annually in the USA [4]. There is an urgent need for a safe, effective and affordable prophylactic vaccine that could help to control the global epidemic and decrease the burden on healthcare systems.

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