Inter-epitope spacer variation within polytopic L2-based human papillomavirus antigens affects immunogenicity

Area of Science:

• Vaccinology
• Immunology
• Structural Biology

Background:

• Human papillomavirus (HPV) minor capsid protein L2 is a promising vaccine antigen.
• Existing L2-based nanoparticle antigens (PANHPVAX, CUT-PANHPVAX) show variable neutralizing antibody responses.
• Optimization of L2 antigen immunogenicity is crucial for effective HPV vaccines.

Purpose of the Study:

• To investigate the impact of six distinct glycine-proline spacers on the immunogenicity of L2-based HPV vaccine antigens.
• To identify specific spacer variants that enhance neutralizing antibody responses against HPV.

Main Methods:

• Development of L2-based nanoparticle antigens with varying glycine-proline spacers.
• Assessment of immunogenicity in a mouse model using pseudovirus-based neutralization assays (PBNAs).
• Quantification of total anti-L2 antibody levels via ELISA and analysis of monoclonal antibody (mAb) avidity using Surface Plasmon Resonance (SPR).

Main Results:

• Spacer variants differentially influenced antigen immunogenicity, with M8merV6 and C12merV6 showing superior neutralizing antibody induction.
• A correlation was observed between total anti-L2 antibody levels and neutralizing antibody levels for most sera.
• Monoclonal antibody affinity to specific spacer variants correlated well with their capacity for neutralizing antibody induction, suggesting affinity as a predictor of immunogenicity.

Conclusions:

• Glycine-proline spacers significantly impact the immunogenicity of L2-based HPV vaccine antigens.
• Specific spacer variants enhance the induction of broadly neutralizing antibodies.
• Monoclonal antibody affinity assays can predict the immunogenicity of L2-based antigens, guiding future HPV vaccine optimization.