Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data

Vaccines composed of virus-like particles (VLPs) made from the L1 major capsid protein of specific HPV types induce a polyclonal antibody response. In the clinical trials of the quadrivalent vaccine, antibodies to the HPV L1 VLPs were measured by a competitive Luminex immunoassay (cLIA).[1,2] This type-specific assay measures antibody binding to a single neutralizing epitope for each HPV-type VLP, that is, it measures a subset of the total immune response to quadrivalent HPV VLP vaccination.[1, 2] Other immunoassays have also been developed that measure total IgG antibody binding to HPV VLPs.[3]

A recent study illustrated potential important differences in serologic assays utilized in the clinical trials of the two currently available HPV VLP vaccines (quadrivalent and bivalent).[4] The conclusion of Brown and coworkers was "Differences in seropositivity status are attributed to the measurement parameters and sensitivity of the individual immunoassays and do not indicate reduced anti-HPV18 protective antibodies." In the study by Brown and coworkers, the same sera from women vaccinated with the quadrivalent HPV vaccine were tested in both the total IgG LIA and the cLIA assays. Seropositivity for HPV18 remained high (96.7%) in the total IgG LIA at 48 months, but was 64.8% in the cLIA. This study illustrates potential important differences in serologic assays utilized in the clinical trials of the two currently available HPV VLP vaccines.

Recently, the CDC published a review of the systems in place or being established for post-licensure monitoring of HPV vaccines in the US.[5] A summary of the post-licensure safety and effectiveness studies being conducted in collaboration with the vaccine’s manufacturers and marketers (Merck and Co., Inc., Sanofi Pasteur MSD) as well as other known independent initiatives in Europe, Canada, and Australia have also been published.[6]

The understanding of the antibody responses to these vaccines is not complete, and there is no established immune correlate of protection or antibody threshold that correlates with protection against HPV infection or disease.[4] In addition, there is no standardized commercially available assay to measure antibody levels. The surveillance efforts for the quadrivalent vaccine represent one of the most comprehensive vaccine surveillance programs to date and will ultimately assess its long-term safety and effectiveness in vaccinated populations.

References

1. Opalka D, Lachman CE, MacMullen SA et al. Simultaneous quantitation of antibodies to neutralizing epitopes on virus-like particles for human papillomavirus types 6, 11, 16 and 18 by a multiplexed luminex assay. Clin Diagn Lab Immunol 2003;10(1):108-115.

2. Dias D, Van Doren J, Schlottmann S et al. Optimization and validation of a multiplexed luminex assay to quantify antibodies to neutralizing epitopes on human papillomavirus 6, 11, 16 and 18. Clin Diagn Lab Immunol 2005;12(8):959-969.

3. Opalka D, Matys K, Bojczuk P et al. Multiplexed serologic assay for nine anogenital human papillomavirus types. Clin Vaccine Immunol 2010;17(5):818-827.

4. Brown DR, Garland SM, Ferris DG et al. The humoral response to Gardasil(R) over four years as defined by Total IgG and competitive Luminex immunoassay. Hum Vaccin 2011;7(2):epub ahead of print.

5. Markowitz LE, Hariri S, Unger ER, Saraiya M, Datta SD, Dunne EF. Post-licensure monitoring of HPV vaccine in the United States. Vaccine 2010;28(30):4731-4737.

6. Bonanni P, Cohet C, Kjaer SK et al. A summary of the post-licensure surveillance initiatives for GARDASIL/SILGARD(R). Vaccine 2010;28(30):4719-4730.