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Research Paper

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

Judith F. Smith, Michelle Brownlow, Martha Brown, Rose Kowalski, Mark T. Esser, Wanda Ruiz, Eliav Barr, Darron R. Brown and Janine T. Bryan

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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.

Authors

Judith F. Smith

Vaccine and Biologics Research, MRL, Merck & Co., Inc.; West Point, PA USA

Michelle Brownlow

Vaccine and Biologics Research, MRL, Merck & Co., Inc.; West Point, PA USA

Martha Brown

Vaccine and Biologics Research, MRL, Merck & Co., Inc.; West Point, PA USA

Rose Kowalski

Vaccine and Biologics Research, MRL, Merck & Co., Inc.; West Point, PA USA

Mark T. Esser

Vaccine and Biologics Research, MRL, Merck & Co., Inc.; Wayne, PA USA

Wanda Ruiz

Vaccine and Biologics Research, MRL, Merck & Co., Inc.; Wayne, PA USA

Eliav Barr

Clinical Research, MRL, Merck & Co, Inc.; Upper Gwynedd, PA USA

Darron R. Brown

Indiana University, Dept. of Medicine, Infectious Disease Division; Indianapolis, IN USA

Janine T. Bryan

Vaccine and Biologics Research, MRL, Merck & Co., Inc.; West Point, PA USA

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.