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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.

SUBMITTER: Toft L

PROVIDER: S-EPMC4896591 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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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.

Toft Lars L Tolstrup Martin M Müller Martin M Sehr Peter P Bonde Jesper J Storgaard Merete M Østergaard Lars L Søgaard Ole S OS

Human vaccines & immunotherapeutics 20140219 5

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 n ...[more]

PMID: 24553190

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Project description:BackgroundThe current generation of Human Papillomavirus (HPV) vaccines, Cervarix® and Gardasil®, exhibit a high degree of efficacy in clinical trials against the two high-risk (HR) genotypes represented in the vaccines (HPV16 and HPV18). High levels of neutralizing antibodies are elicited against the vaccine types, consistent with preclinical data showing that neutralizing antibodies can mediate type-specific protection in the absence of other immune effectors. The vaccines also confer protection against some closely related non-vaccine HR HPV types, although the vaccines appear to differ in their degree of cross-protection. The mechanism of vaccine-induced cross-protection is unknown. This study sought to compare the breadth and magnitudes of neutralizing antibodies against non-vaccine types elicited by both vaccines and establish whether such antibodies could be detected in the genital secretions of vaccinated individuals.Methods and findingsSerum and genital samples were collected from 12-15 year old girls following vaccination with either Cervarix® (n = 96) or Gardasil® (n = 102) HPV vaccine. Serum-neutralizing antibody responses against non-vaccine HPV types were broader and of higher magnitude in the Cervarix®, compared to the Gardasil®, vaccinated individuals. Levels of neutralizing and binding antibodies in genital secretions were closely associated with those found in the serum (r = 0.869), with Cervarix® having a median 2.5 (inter-quartile range, 1.7-3.5) fold higher geometric mean HPV-specific IgG ratio in serum and genital samples than Gardasil® (p = 0.0047). There was a strong positive association between cross-neutralizing antibody seropositivity and available HPV vaccine trial efficacy data against non-vaccine types.ConclusionsThese data demonstrate for the first time that cross-neutralizing antibodies can be detected at the genital site of infection and support the possibility that cross-neutralizing antibodies play a role in the cross-protection against HPV infection and disease that has been reported for the current HPV vaccines.Trial registrationClinicalTrials.gov NCT00956553.

Project description:Gardasil®, a quadrivalent vaccine targeting low-risk (6, 11) and high-risk (16, 18) human papillomaviruses (HPV), has been offered to 11-14 year-old schoolgirls in Switzerland since 2008. To evaluate its success and its potential impact on cervical cancer screening, HPV genotypes were examined in 18-year-old girls five years later (sub-study 1) and in outpatients participating to cervical cancer screening before and after vaccine implementation (sub-study 2).For sub-study 1, 3726 females aged 18 in 2013 were invited to fill a questionnaire on personal demographics and HPV risk factors and to provide a self-collected cervicovaginal sample for HPV genotyping and Chlamydia trachomatis PCR. Personal data were evaluated by univariable and multivariable statistics. In sub-study 2, the proportion of the vaccine-type HPV among anogenital HPV was examined with archived genotyping data of 8039 outpatients participating to cervical cancer screening from 1999 till 2015. The yearly evolution of this proportion was evaluated by segmented logistic regression.690 (18.5%) women participated to sub-study 1 and 327 (8.8%) provided a self-collected sample. Prevalence of Chlamydia trachomatis (4.6%) and demographics confirmed that the subjects were representative of sexually-active Swiss young women. Vaccine (five-year coverage: 77.5%) was preferentially accepted by contraceptive-pill users (P = 0.001) and samples were mainly provided by sexually-active subjects (P < 0.001). The proportion (4%) of the vaccine-type HPV in this population was lower than in sub-study 2 outpatients (n = 849, <26 years old) in the pre-vaccine era (25.7%). The proportion of the high-risk vaccine-type HPV decreased significantly (59%, P = 0.0048) in the outpatients during the post-vaccine era, yet this decrease was restricted to those aged less than 26 years (n = 673, P < 0.0001).The low proportion of vaccine-type HPV in 18-year-old females and its rapid decrease in young women participating to cervical cancer screening extend the success of HPV vaccination to Switzerland. Our data suggest that cervical cancer screening is now entering a stage of reduced proportion of HPV16 and/or 18 in samples reported positive by cytology. In view of the high likelihood of reduced clinical specificity of cytology, primary screening modalities involving HPV testing and cytology should now be re-evaluated in Switzerland.

Project description:BACKGROUND:Human papillomavirus (HPV) vaccines confer protection against the oncogenic genotypes HPV16 and HPV18 through the generation of type-specific neutralizing antibodies raised against virus-like particles (VLP) representing these genotypes. The vaccines also confer a degree of cross-protection against HPV31 and HPV45, which are genetically-related to the vaccine types HPV16 and HPV18, respectively, although the mechanism is less certain. There are a number of humoral immune measures that have been examined in relation to the HPV vaccines, including VLP binding, pseudovirus neutralization and the enumeration of memory B cells. While the specificity of responses generated against the vaccine genotypes are fairly well studied, the relationship between these measures in relation to non-vaccine genotypes is less certain. METHODS:We carried out a comparative study of these immune measures against vaccine and non-vaccine genotypes using samples collected from 12-15 year old girls following immunization with three doses of either Cervarix® or Gardasil® HPV vaccine. RESULTS:The relationship between neutralizing and binding antibody titers and HPV-specific memory B cell levels for the vaccine genotypes, HPV16 and HPV18, were very good. The proportion of responders approached 100% for both vaccines while the magnitude of these responses induced by Cervarix® were generally higher than those following Gardasil® immunization. A similar pattern was found for the non-vaccine genotype HPV31, albeit at a lower magnitude compared to its genetically-related vaccine genotype, HPV16. However, both the enumeration of memory B cells and VLP binding responses against HPV45 were poorly related to its neutralizing antibody responses. Purified IgG derived from memory B cells demonstrated specificities similar to those found in the serum, including the capacity to neutralize HPV pseudoviruses. CONCLUSIONS:These data suggest that pseudovirus neutralization should be used as the preferred humoral immune measure for studying HPV vaccine responses, particularly for non-vaccine genotypes.

Dataset Information

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.

Publications

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.

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