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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
Comparative immunogenic and structural analysis of virus-like particle and inactivated whole-virion vaccines against
Kota Senpuku1,2, Yuta Kunishima2,3, Mika Hirose4
1Laboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Abstract:
Enterovirus D68 (EV-D68) primarily causes respiratory illnesses and has been implicated in acute flaccid myelitis. Although virus-like particle (VLP) and traditional inactivated whole-virion (IWV) vaccines have demonstrated efficacy in mice, their immunological differences remain undetermined. Here, we directly compared the immunogenic and structural properties of VLP and IWV vaccines derived from the same EV-D68 strain under identical conditions. Although VLP induced significantly lower levels of EV-D68-specific IgG than IWV, neutralizing antibody titers and protective effects against viral challenge were comparable between the two groups in mice. Passive transfer experiments in neonatal mice further confirmed protection against lethal infection for both vaccine groups. Notably, in contrast to the IWV vaccine, the VLP vaccine elicited antibodies that preferentially recognized a limited subset of epitopes. Cryo-electron microscopy analyses revealed that VLPs structurally resemble the native virus but display distinct features in regions corresponding to epitopes that show differential antibody reactivity between VLP and IWV vaccines. By integrating structural and immunological analyses, we established a mechanistic framework linking capsid architecture to vaccine-induced antibody specificity. These findings suggest that VLP is a promising EV-D68 vaccine antigen with distinct epitope recognition profiles driven by structural characteristics.
Insights
This study compared Enterovirus D68 (EV-D68) virus-like particle (VLP) and inactivated whole-virion (IWV) vaccines. Both vaccine types showed comparable protection, but VLPs elicited antibodies recognizing specific epitopes due to structural differences.
Area of Science:
- Virology
- Vaccinology
- Structural Biology
Background:
- Enterovirus D68 (EV-D68) is a significant pathogen causing respiratory illness and acute flaccid myelitis.
- Existing EV-D68 vaccines, including virus-like particles (VLPs) and inactivated whole-virions (IWVs), show efficacy in preclinical models.
- Direct comparative immunological and structural data between VLP and IWV vaccines for EV-D68 are lacking.
Purpose of the Study:
- To directly compare the immunogenic and structural properties of EV-D68 VLP and IWV vaccines.
- To elucidate the relationship between vaccine structure and antibody epitope specificity.
- To assess the protective efficacy of both vaccine types against EV-D68 infection.
Main Methods:
- Production of VLP and IWV vaccines from the same EV-D68 strain under identical conditions.
- Immunization of mice and assessment of EV-D68-specific IgG and neutralizing antibody titers.
- Passive antibody transfer experiments in neonatal mice to evaluate protection.
- Cryo-electron microscopy (Cryo-EM) for structural analysis of VLPs.
- Epitope mapping to determine antibody recognition profiles.
Main Results:
- Both VLP and IWV vaccines induced comparable neutralizing antibody titers and protection against EV-D68 challenge in mice.
- VLP vaccines elicited significantly lower levels of total IgG compared to IWV vaccines.
- Antibodies generated by VLP vaccines preferentially recognized a distinct subset of epitopes compared to IWV vaccines.
- Cryo-EM revealed structural differences in VLP epitopes correlating with differential antibody reactivity.
Conclusions:
- EV-D68 VLP vaccines are a promising alternative, offering comparable protection to IWV vaccines.
- Vaccine-induced antibody specificity is influenced by the structural characteristics of the antigen.
- Understanding the structure-epitope relationship can guide the development of more targeted and effective vaccines.
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