Recombinant Full-Length Hepatitis C Virus E1E2 Dimer Elicits Pangenotypic Neutralizing Antibodies

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Hepatitis C virus (HCV) infection poses a significant global health burden.
• Developing an effective prophylactic HCV vaccine is hampered by the virus's high genetic diversity.
• Identifying immunogens that elicit broad neutralizing antibodies (NAbs) is crucial for vaccine efficacy.

Purpose of the Study:

• To design and produce recombinant E1E2 antigens covering multiple HCV genotypes (1a, 1b, 2a, 3a, 6a).
• To evaluate the immunogenicity and efficacy of these antigens in eliciting pangenotypic antibody responses.
• To assess the potential of a pentavalent vaccine formulation for improved immune response.

Main Methods:

• Production of IgG Fc-tagged recombinant E1E2 antigens from five HCV genotypes using FreeStyle 293-F cells.
• Localization and purification of antigens from cellular membrane extracts.
• Assessment of antigen structure, function, interaction with co-receptors, and blockade of HCV infection.
• Immunization of mice with monovalent and pentavalent antigen formulations, followed by analysis of antibody and T cell responses.

Main Results:

• Purified Fc-E1E2 proteins exhibited correct folding and function, interacting with HCV entry co-receptors and blocking infection.
• Mouse immunization with individual recombinant E1E2 antigens induced pangenotypic antibody responses.
• The pentavalent formulation elicited a more robust and uniform NAb titer and T cell response compared to monovalent antigens.

Conclusions:

• The developed recombinant E1E2 antigens are functional and capable of inducing broad immune responses.
• A pentavalent vaccine strategy shows potential for enhancing NAb titers and T cell responses against diverse HCV genotypes.
• This approach may offer a viable strategy for developing a pangenotypic HCV vaccine and for other viruses with heterogeneous surface glycoproteins.