Modification of human papillomavirus-like particle vaccine by insertion of the cross-reactive L2-epitopes.

Infection with human papillomavirus 16 (HPV16), which is one of the 15 types of HPV causally associated with cervical cancer and accounts for 50% of the cases, can be prevented in a type-specific manner by an HPV16 virus-like particle (VLP) vaccine comprised of particles of the L1 protein alone. We attempted to modify the VLP vaccine by inserting the HPV16 L2-peptides including cross-neutralization epitopes into the L1 polypeptide. The chimeric L1 had, between L1 amino acids (aa) 430 and 433, the L2 sequence of aa 18-38, 56-75, or 96-115 (with the replacements of S at aa 101 and T at aa 112 with L and S, respectively). The three chimeric L1s were each expressed from the recombinant baculovirus in insect Sf9 cells, and the resultant VLPs were characterized. The chimeric VLPs were shown to present the L2-peptides on their surface. By immunizing rabbits with the VLPs, it was shown that they retained capability to induce the antibody neutralizing HPV16 and acquired capability to elicit antibodies cross-neutralizing the infectious HPV18, 31, 52, and 58 pseudovirions. Although the cross-neutralizing titers were lower than the type-specific neutralizing titer, the results suggest that the chimeric VLPs have potential to serve as a vaccine candidate for a broad spectrum of high-risk HPVs.