Antibodies from Women Immunized with Gardasil ® Cross-Neutralize HPV 45 Pseudovirions

Abstract

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 L1 homology between HPV types and it is likely that there is a substantial degree of surface exposed viral epitope similarity. An investigation of vaccine-induced antibody binding and neutralization was undertaken focusing on A7 species members, HPV 18 and 45. Polyclonal sera from Gardasil ® recipients and from HPV 18 L1 VLP recipients were evaluated. Vaccine-induced antibodies were found to cross-neutralize HPV 45 pseudovirions (PsV) in vitro. 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(r) immunization induces antibodies capable of neutralizing HPV 18 PsV and HPV 45 PsV in vitro.

Circulation of human papillomavirus (HPV) genotypes in women from Córdoba, Argentina, with squamous intraepithelial lesions

“…1, although immunization with existing vaccines would cover more than 50% of infections, a high percentage (45.3%) of HR-HPV infections would not be prevented by these vaccines. Although the cross-protection data are encouraging 16,30 , the titers of the neutralizing antibodies for the genotypes not included in the formulation are about ten times lower than those for the genotypes that are included. This generates uncertainty about whether they will disappear more rapidly than the specific antibodies.…”

“…It has also been reported that the protection against HPV 52 and HPV 58 (two of the four most frequent HR-HPV in our study) is not significant. These data have led some authors to infer that the cross-protection seems to be limited 27,30 .…”

The humoral response to Gardasil over four years as defined by Total IgG and competitive Luminex immunoassay

“…46,47 The H18.R5 antibody has been shown to recognize both HPV 18 and HPV 45 conformational VLPs and neutralize both A7 species members. 46,48 This observation suggests variability between HPV types in utilization of immunodominant epitope on L1 VLPs. Thus, some women may make highly efficient, neutralizing antibodies to epitopes on HPV 18 VLPs that differ from the HPV 18 type-specific epitope monitored in the cLIA by H18.…”

Naturally Occurring Major and Minor Capsid Protein Variants of Human Papillomavirus 45 (HPV45): Differential Recognition by Cross-Neutralizing Antibodies Generated by HPV Vaccines

“…Structural alterations of the external surface topography of L1 can be conferred by minor sequence differences between genotypes (13), supporting observations that almost all neutralizing monoclonal antibodies (MAbs) that target these external surfaces are type specific (14)(15)(16)(17). Nevertheless, functional antibody cross-reactivity is a common feature of sera from recipients of the Cervarix (bivalent) and Gardasil (quadrivalent) vaccines (18)(19)(20)(21)(22) and may be responsible for conferring HPV vaccine-induced cross-protection (23).…”