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Detection of Neutralization-sensitive Epitopes in Antigens Displayed on Virus-Like Particle VLP-Based Vaccines Using a Capture Assay
Published on: February 10, 2022
Comparison of structure and immunogenicity of CVB1-VLP and inactivated CVB1 vaccine candidates
Saana Soppela1, Zlatka Plavec2, Stina Gröhn1
1Tampere University.
Insights
Developing a formalin-inactivated Coxsackievirus B1 (CVB1) vaccine for intranasal administration shows promise for mucosal immunization. This approach elicits robust immune responses, offering a potential new strategy against CVB1-related diseases.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- Coxsackievirus B1 (CVB1) causes significant human diseases like myocarditis and meningitis.
- Currently, no vaccines are available for human use against CVB1.
- Developing effective CVB1 vaccines is a critical public health need.
Purpose of the Study:
- To evaluate the immunogenicity of virus-like particle (VLP) and inactivated whole-virus vaccines for CVB1.
- To investigate the potential of epigallocatechin-3-gallate (EGCG) as a mucosal adjuvant.
- To compare subcutaneous and intranasal administration routes for CVB1 vaccines.
Main Methods:
- Mice were immunized with CVB1-VLPs and formalin-inactivated CVB1 virus via subcutaneous and intranasal routes.
- Vaccines were formulated with and without commercial and experimental adjuvants, including EGCG.
- Humoral, cellular, and mucosal immune responses were assessed.
- Cryo-electron microscopy was used to determine particle structures.
Main Results:
- Intranasal administration of formalin-inactivated CVB1 induced strong humoral, cellular, and mucosal immune responses.
- EGCG showed adjuvant properties for CVB1-VLPs via parenteral routes but limited efficacy intranasally.
- Cryo-electron microscopy revealed structural differences between inactivated virus and VLPs, providing insights for future vaccine design.
Conclusions:
- Formalin-inactivated CVB1 vaccine is a promising candidate for mucosal immunization programs.
- Intranasal administration of inactivated CVB1 effectively elicits protective immune responses.
- Further structural engineering of CVB1-VLPs could enhance their mucosal immunogenicity.
Abstract:
Coxsackievirus B1 (CVB1) is a common cause of acute and chronic myocarditis, dilated cardiomyopathy and aseptic meningitis. However, no CVB-vaccines are available for human use. In this study, we investigated the immunogenicity of virus-like particle (VLP) and inactivated whole-virus vaccines for CVB1 when administrated to mice via either subcutaneous or intranasal routes formulated with and without commercial and experimental adjuvants. Here, the potential of utilizing epigallocatechin-3-gallate (EGCG) as a mucosal adjuvant synergistically with its ability to inactivate the virus were investigated. EGCG had promising adjuvant properties for CVB1-VLP when administered via the parenteral route but limited efficacy via intranasal administration. However, intranasal administration of the formalin-inactivated virus induced high CVB1-specific humoral, cellular, and mucosal immune responses. Also, based on CVB1-specific IgG-antibody responses, we conclude that CVB1-VLP can be taken up by immune cells when administrated intranasally and further structural engineering for the VLP may increase the mucosal immunogenicity. The preparations contained mixtures of compact and expanded A particles with 85% expanded in the formalin-inactivated virus, but only 52% in the VLP observed by cryogenic electron microscopy. To correlate the structure to immunogenicity, we solved the structures of the CVB1-VLP and the formalin-inactivated CVB1 virus at resolutions ranging from 2.15 A to 4.1 A for the expanded and compact VLP and virus particles by image reconstruction. These structures can be used in designing mutations increasing the stability and immunogenicity of CVB1-VLP in the future. Overall, our results highlight the potential of using formalin inactivated CVB1 vaccine in mucosal immunization programs and provide important information for future development of VLP-based vaccines against all enteroviruses.
