Introduction: Current human papillomavirus (HPV) vaccines consist of virus-like particles (VLPs) which are based on the L1 protein, but they are produced by different expression systems and use... Show moreIntroduction: Current human papillomavirus (HPV) vaccines consist of virus-like particles (VLPs) which are based on the L1 protein, but they are produced by different expression systems and use different adjuvants. We performed in-depth immunophenotyping of multiple innate and adaptive immune cells after vaccination with bivalent versus nonavalent HPV vaccines. Method: Twenty pre-menopausal HPV-seronegative women were enrolled and randomized to receive three-doses of either the bivalent or the nonavalent HPV vaccine. Blood samples were collected at multiple time points from baseline up to 7 months after first vaccination. Four extensive EuroFlow flow cytometry antibody panels were used to monitor various immune cell subsets. Additionally, HPV-specific memory B- and T cells were determined by ELISPOT and HPV-specific antibody levels were measured by a VLP-based multiplex immunoassay. Results: In both cohorts, the numbers of plasma cells expanded in the first week after both primary and tertiary vaccination. HPV16 and HPV18-specific antibody levels and memory B and T-cell responses were higher in the bivalent than in the nonavalent vaccinees one month post third vaccination. For HPV31 and HPV45-specific antibody levels this pattern was reversed. Monocytes showed an expansion one day after vaccination in both cohorts but were significantly higher in the bivalent vaccine cohort. Large heterogeneity in responses of the other cell subsets was observed between donors. Conclusion: This pilot study showed a consistent response of monocytes and plasma cells after vaccination and a considerable variation in other circulating immune cells in both types of HPV vaccines between donors. Show less
This thesis contains a variety of information about the natural and vaccine induced immunity against the human papillomavirus. The spontaneously induced HPV-specific humoral response after... Show moreThis thesis contains a variety of information about the natural and vaccine induced immunity against the human papillomavirus. The spontaneously induced HPV-specific humoral response after infection was assessed in population-based studies. The vaccine-induced changes in HPV-seroprevalence among the HPV unvaccinated Dutch population aged 0-89 years, where we compared the HPV-seroprevalence before the introduction of the HPV vaccine with data of approximately six years post-implementation of the national HPV vaccination program. Also, the HPV immune status of the Dutch Caribbean population just after introduction of HPV vaccination was determined. Moreover, the longitudinal relation between the hr-HPV antibody levels and the prevalence of HPV infections in three-dose vaccinated girls were studied. And more insight was gained into humoral and cellular immune responses after just a one-dose of the HPV vaccine. At last, the kinetics of innate and adaptive immune responses directly after vaccination different HPV vaccines were investigated. In the coming years some important changes are expected regarding HPV screening and vaccination. The effectiveness of the one-dose schedule will become clear as clinical trials end. In the Netherlands, a sex-neutral vaccination will be implemented soon. These changes will need to be monitored to provide scientific answers about the effectiveness and immunogenicity. Show less
Grein, I.H.R.; Pinto, N.F.; Lobo, A.; Groot, N.; Sztajnbok, F.; Silva, C.A.A. da; ... ; Pileggi, G. 2020
ObjectiveThis study aimed to assess the safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccination in childhood-onset systemic lupus erythematosus (cSLE) patients... Show moreObjectiveThis study aimed to assess the safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccination in childhood-onset systemic lupus erythematosus (cSLE) patients.MethodsVolunteer cSLE patients aged 9-20 years and healthy controls (HC) were enrolled to receive a two- or three-dose qHPV vaccination schedule from March 2014 to March 2016. Study visits were performed before the first dose, one month after the second and third doses and one year after the first dose. In each study visit, disease activity and adverse events following vaccination were analyzed, and a serum sample was collected for testing antibody concentrations. Participant recruitment was conducted in 15 Brazilian paediatric rheumatology units. Of the 256 cSLE patients included, 210 completed the two- or three-dose schedules; 15 had previously received one dose, and 18 had received two doses of the vaccine. The analysis was based on intention-to-treat so that participants who did not complete the entire study protocol were also included.ResultsNo severe adverse events were related to the vaccination. Disease activity was generally low and remained stable or even improved. The HC presented 100% seropositivity to HPV16 and HPV18, whereas the two- and three-dose cSLE groups presented 93% and 83% versus 97% and 91%, respectively. One year after the first dose, seropositivity of the three-dose cSLE group was 91% to HPV16 and 84% to HPV18.ConclusionsHPV vaccination in cSLE patients is safe and immunogenic. Since the seropositivity to HPV16 and HPV18 was higher for the three-dose schedule group, this regimen should be recommended for cSLE patients. Show less
Hoes, J.; Pasmans, H.; Knol, M.J.; Donken, R.; Marm-Wattimena, N. van; Schepp, R.M.; ... ; Melker, H.E. de 2020
The bivalent human papillomavirus (HPV) vaccine is highly effective and induces robust serological responses. Using a Dutch prospective cohort initiated in 2009, including 744 vaccinated and 294... Show moreThe bivalent human papillomavirus (HPV) vaccine is highly effective and induces robust serological responses. Using a Dutch prospective cohort initiated in 2009, including 744 vaccinated and 294 unvaccinated girls (1993-1994) who provide a vaginal self-swab sample, serum sample, and questionnaire yearly, we report a high, persisting antibody response up to 9 years after vaccination for vaccine types HPV-16 or HPV-18. Antibodies against nonvaccine HPV types 31, 33, 45, 52, and 58 were lower but still significantly higher than in unvaccinated individuals. This was also reflected in the seroprevalence. We compared participant characteristics and antibody levels between vaccinated women with and those without HPV infections 1 year before infection (204 incident and 64 persistent infections), but we observed no consistent difference in type-specific antibody levels. Having a high-risk HPV infection was associated with sexual risk behavior and smoking 1 year before infection. Although high antibody levels are necessary for protection, our study suggests that on the individual level other factors such as HPV exposure or antibody avidity could be important. Show less
Introduction: In 2009, girls-only HPV16/18 vaccination was introduced in the Netherlands which has achieved 46-61% uptake. Heterosexual men have benefitted from herd protection, but it is unknown... Show moreIntroduction: In 2009, girls-only HPV16/18 vaccination was introduced in the Netherlands which has achieved 46-61% uptake. Heterosexual men have benefitted from herd protection, but it is unknown whether men who have sex with men (MSM) also benefit from herd effects of the girls-only HPV16/18 vaccination program. Because MSM bear a high HPV-related disease burden, countries might consider targeted vaccination for MSM. To study possible herd effects and prior HPV exposure at a potential moment of vaccination, we assessed trends in the HPV prevalence and proportions (sero)negative for the various vaccine types among young MSM visiting sexual health centers (SHCs).Methods: We used data from MSM included in PASSYON study years 2009-2017. In this biennial cross-sectional study among visitors of SHCs aged 16-24 years, MSM provided a penile and anal swab for HPV DNA testing (including vaccine types HPV6/11/16/18/31/33/45/52/58) and blood for HPV antibody testing (HPV16/18/31/33/45/52/58).Results: In total 575 MSM were included, with a median of 22 years of age and 15 lifetime sex partners and 3.5% HIV positive. Trends in penile or anal HPV prevalence during 2009-2017 were statistically non-significant for all vaccine types. Of the 455 MSM with a penile and anal swab, 360 (79%), 283 (62%) and 242 (53%) were HPV DNA negative at both anatomical sites for HPV16/18, HPV6/11/16/18 and HPV6/11/16/18/31/33/45/52/58 respectively. Among MSM who were HPV16/18 and HPV16/18/31/33/45/52/58 DNA negative and were tested for serology (n = 335 and 279 respectively), 82% and 71% were also seronegative for the respective types.Discussion: There were no significant declines in the HPV prevalence among MSM up to eight years after introduction of girls-only HPV16/18 vaccination, indicating that MSM are unlikely to benefit largely from herd effects from girls-only vaccination. Most MSM were vaccine-type DNA negative and seronegative, suggesting that vaccination of young MSM visiting SHCs could still be beneficial. (C) 2020 The Author(s). Published by Elsevier Ltd. Show less
Vos, R.A.; Pasmans, H.; Tymchenko, L.; Janga-Jansen, A.V.A.; Baboe-Kalpoe, S.; Hulshof, K.; ... ; Klis, F.R.M. van der 2020
Background: Incidence and mortality of human papillomavirus (HPV)-related cancers differs geographically, with high rates in Caribbean countries. Seroepidemiological data provide information on... Show moreBackground: Incidence and mortality of human papillomavirus (HPV)-related cancers differs geographically, with high rates in Caribbean countries. Seroepidemiological data provide information on lifetime cumulative HPV exposure and contributing risk factors, but has not been available yet for Caribbean Netherlands (CN), comprising the islands Bonaire, St. Eustatius and Saba. Therefore, a cross-sectional population-based serosurveillance study was performed in this (recently girls-only HPV-vaccinated) population in 2017.Methods: Blood samples from participants (n = 1,823, 0-90 years) were tested for seven high-risk (hr)-HPV-specific IgG-antibodies using a VLP-based multiplex-immunoassay. Risk factors for HPV-seropositivity were analysed among persons unvaccinated aged >= 15 years who ever had sex (n = 1,080).Results: Among unvaccinated individuals aged >= 15 years, overall seropositivity was high (34%), with over half of them being seropositive for >= 2 hr-HPV types, and HPV16 and 52 being most prevalent (13%). Seroprevalence was substantial higher in unvaccinated women (51%) than men (18%), predominantly peaking in women aged 20-59 years, and was highest on St. Eustatius (38%). Besides age and sex, sexual risk factors were associated with HPV-seropositivity.Conclusions: In accordance with the Caribbean region, seroprevalence of multiple hr-HPV types was high in CN. These data corroborate the decision regarding introduction of a sex-neutral HPV-vaccination program and the relevance for considering a population-based cervical cancer screening program. (C) 2020 The Authors. Published by Elsevier Ltd. Show less
