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.

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.