VP1-141 is a determinant of a Vero cell-adapted Coxsackievirus A10 for vaccine development

Area of Science:

• Virology
• Vaccinology
• Molecular Biology

Background:

• Coxsackievirus A10 (CVA10) causes hand, foot, and mouth disease (HFMD) and is a significant enterovirus target for vaccine development.
• Current CVA10 strains are difficult to propagate in Vero cells, hindering vaccine production.
• A multivalent vaccine for HFMD requires efficient culture systems for multiple enteroviruses.

Purpose of the Study:

• To develop a CVA10 strain adapted for efficient propagation in Vero cells for vaccine development.
• To identify the key viral determinants responsible for Vero cell adaptation.
• To assess the immunogenicity of the adapted CVA10 strain and its potential in multivalent vaccines.

Main Methods:

• Isolation and adaptation of a CVA10 strain (CVA10-V) in Vero cells.
• Propagation and purification of CVA10-V full particles (F-particles) and empty particles.
• Immunization of a mouse model with CVA10-V F-particles, alone and combined with EV-A71.
• Construction and analysis of infectious CVA10 clones with specific P1 protein mutations.

Main Results:

• A highly Vero cell-adapted CVA10 strain (CVA10-V) was successfully generated.
• CVA10-V F-particles induced strong immunogenicity in mice, while empty particles did not.
• Co-immunization with CVA10-V F-particles and EV-A71 elicited good neutralization responses to both viruses.
• A single amino acid substitution (VP1-141) was identified as critical for CVA10 adaptation to Vero cells, affecting viral attachment.

Conclusions:

• The Vero-adapted CVA10-V strain is suitable for large-scale vaccine production using Vero cell culture.
• The identified VP1-141 substitution is a key determinant for CVA10 Vero cell adaptation.
• This adapted strain is a valuable component for developing effective multivalent HFMD vaccines.