Minor capsid protein of human genital papillomaviruses contains subdominant, cross-neutralizing epitopes

Vaccination with virus-like particles (VLP), comprising both L1 and L2 of human papillomavirus (HPV) genital types 6, 16, and 18, induces predominantly type-specific neutralizing antibodies. L2 polypeptide vaccines protect animals against experimental challenge with homologous papillomavirus and cross-reactive epitopes are present in HPV L2. To assess L2-specific cross-neutralization of HPV genotypes, sheep were immunized with purified, bacterially expressed HPV6, 16, or 18 L2. In addition to neutralizing the homologous HPV type in vitro, antisera to each HPV L2 also cross-neutralized both heterologous HPV types. This suggests that unlike VLP-based prophylactic HPV vaccines, an L2 polypeptide vaccine may provide broad-spectrum protection.