Human papillomavirus (HPV) types 6, 11, 16 and 18 L1 virus-like particles (VLPs) have been used to generate the prophylactic quadrivalent vaccine, Gardasil®. There is a high degree of homology within the L1 major capsid protein sequence of genital HPV types and it is therefore likely that there is a substantial degree of antigenic similarity of the surface exposed epitopes on the virion particles or on VLPs. It is possible then, that antibodies induced by immunization with Gardasil® could bind, and even neutralize HPV types that are closely related to the vaccine types. An investigation of antibody binding and neutralization was undertaken focusing on two members of the A7 species, HPV 18 and HPV 45. Polyclonal sera from Gardasil® recipients and from HPV 18 L1 VLP recipients were evaluated. Utilizing the pseudovirus neutralization assay developed by the National Cancer Institute, antibodies induced by the vaccines were found to cross-neutralize HPV 45 pseudovirions (PsV). Examination of a panel of monoclonal antibodies made against L1 VLPs revealed the presence of conformational, neutralizing epitopes on the surface of VLPs that may be shared between HPV 18 and HPV 45. These data demonstrate that Gardasil® immunization induces antibodies capable of neutralizing HPV 18 PsV and HPV 45 PsV in vitro.