Optimization of multimeric human papillomavirus L2 vaccines

Area of Science:

• Immunology
• Virology
• Vaccine Development

Background:

• Human papillomavirus (HPV) L1 virus-like particles (VLPs) induce type-specific neutralizing antibodies.
• The minor capsid protein L2, particularly its amino terminus, contains broadly protective epitopes.
• Developing vaccines that elicit broad-spectrum immunity against diverse HPV types is a critical goal.

Purpose of the Study:

• To define protective epitopes within the amino terminus of HPV type 16 L2.
• To design and evaluate novel L2-based fusion proteins for enhanced immunogenicity and broader protection.
• To investigate the contribution of specific L2 regions to vaccine efficacy.

Main Methods:

• Passive transfer of antisera against specific HPV16 L2 peptides in mice challenged with HPV16.
• Vaccination of mice with L2 fusion proteins (11-88×8 and 13-47×15) and their variants (11-88×8Δ, 11-88×8ΔPADRE).
• Assessment of antibody titers and neutralizing activity against various HPV types.

Main Results:

• Antisera to HPV16 L2 peptides 17-36, 32-51, and 65-81 conferred significant protection against HPV16 challenge.
• The 11-88×8 fusion protein was more immunogenic than 13-47×15, highlighting the importance of the 65-81 epitope.
• Deletion of the non-protective 47-66 region (11-88×8Δ) reduced immunogenicity, indicating its contribution to overall vaccine response.

Conclusions:

• The amino terminus of HPV16 L2 contains critical protective epitopes, notably residues 65-81.
• L2-based fusion proteins, like 11-88×8, can induce broader and more potent immune responses than L1 VLPs.
• The 47-66 region, while not a key protective epitope, plays a role in the immunogenicity of L2 fusion protein vaccines.