Abstract B93: Concatenated multitype L2 fusion proteins as prophylactic human papillomavirus vaccines

Abstract

Abstract B93 Vaccination with minor capsid protein L2, is known to induce antibodies that cross-neutralize diverse papillomavirus types.However, neutralizing titers against the homologous type are generally much higher than the titers against heterologous types. We hypothesized that vaccination with concatenated multi-type L2 fusion proteins derived from known cross-protective epitopes of several divergent HPV types might increase immunity across medically significant HPV genotypes. Here, the antibody responses of mice and rabbits to vaccination with HPV16 L2 polypeptides comprising residues 1-88 or 11-200, was compared with multi-type L2 fusion proteins, namely 11-200x3 types (HPV6, 16, 18), 11-88x5 types (HPV1, 5, 6,16, 18), or 17-36x22 types (5 cutaneous, 2 mucosal low risk and 15 oncogenic types), and with a licensed quadrivalent HPV L1 virus-like particle (VLP) vaccine, Gardasil. The monotype L2 polypeptides generated robust neutralization titers against HPV16 but lower titers against other HPV types. In contrast, the antisera to the multi-type L2 fusion proteins, notably 11-200x3 and 11-88x5, induced high neutralizing titers against all heterologous HPVs tested. However, in mice, these neutralizing titers were consistently lower than those to L1 VLP. The in vitro neutralization titers elicited by vaccination with 11-200x3 in different adjuvant combinations tested were not significantly different at two weeks after immunization. However, the vaccines formulated in GPI-0100 adjuvant or alum and ISS 1018 protected mice against HPV16 challenge at four months after immunization in the same manner as HPV16 L1 VLP, whereas 11-200x3 alone or formulated with either alum or ISS 1018 alone was significantly less effective. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B93.