Comparison of the immunogenicity of Cervarix® and Gardasil® human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults

Abstract

Individuals infected with human immunodeficiency virus (HIV) have excess risk of developing human papillomavirus (HPV)-related disease. A substantial fraction of HPV-associated cancers is caused by HPV serotypes not included in the currently available vaccines. Among healthy women, both Cervarix(®) (HPV-16/18, GlaxoSmithKline Biologicals, GSK) and Gardasil(®) (HPV-6/11/16/18, Merck) have demonstrated partial cross-protection against certain oncogenic non-vaccine HPV-types. Currently, there are no available data on vaccine-induced cross-protection in men and little is known about cross-reactive immunity after HPV-vaccination of HIV-infected individuals. In an investigator-initiated trial, we randomized 91 HIV-positive men and women to receive vaccination with Cervarix(®) or Gardasil(®). The HPV-DNA status of the participants was determined with pcr before and after immunization. Cross-reactive antibody responses against HPV-31, HPV-33, and HPV-45 were evaluated for up to 12 months using a pseudovirion-based neutralization assay (PBNA). Geometric mean antibody titers (GMTs) were compared among vaccine groups and genders at 7 and 12 months.: Both vaccines induced anti-HPV-31, -33, and -45 neutralizing antibodies in participants who were seronegative and HPV-DNA negative for those types at study entry. Geometric mean antibody titers were comparable between vaccine groups. Interestingly, anti-HPV-31 and -33 antibody titers were higher among women compared with men at 7 and 12 months.: In conclusion, both licensed HPV-vaccines induced cross-neutralizing antibodies against frequent oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults, and women had greater serological responses against HPV-31 and -33 compared with men.

Trial registration: ClinicalTrials.gov NCT01386164.

Keywords: Cervarix; Gardasil; HPV vaccines; cross neutralization; neutralizing antibodies; serology.

Figures

Figure 1. Seropositivity rates for neutralizing anti-HPV-31, -33, and -45 antibodies in baseline HPV-negative cohorts. Seropositivity rates for neutralizing anti-HPV-31, -33, and -45 antibodies measured by Pseudovirion-based neutralization assay at months 7 and 12. (HPV-negative cohorts, seronegative, and DNA-negative at baseline for HPV type analyzed). N, number of evaluable subjects; n, number of seropositive subjects, per vaccine, per timepoint. Percentages indicate seropositivity rates at each timepoint (seropositivity defined as PBNA ED50 > 40). HPV, human papillomavirus; GMTs, geometric mean titers.

Figure 2. Gender-specific geometric mean titers (GMTs) and seropositivity rates for neutralizing anti-HPV-31, -33, and -45 antibodies in baseline HPV-negative cohorts. (A) Gender-specific geometric mean antibody titer computed using the log10 transformation of titers as measured by Pseudovirion-based neutralization assay at months 7 and 12. (HPV-negative cohorts, seronegative, and DNA-negative at baseline for HPV type analyzed). N, number of evaluable subjects. *P < 0.05, **P < 0.001. HPV, human papillomavirus; GMTs, geometric mean titers. (B) Gender-specific seropositivity rates for neutralizing anti-HPV-31, -33, and -45 antibodies measured by Pseudovirion-based neutralization assay at months 7 and 12. (HPV-negative cohorts, seronegative, and DNA-negative at baseline for HPV type analyzed). N, number of evaluable subjects; n, number of seropositive subjects, per gender, per timepoint. Percentages indicate seropositivity rates at each timepoint (seropositivity defined as PBNA ED50 > 40). HPV, human papillomavirus; GMTs, geometric mean titers.