The licensed HPV vaccines are highly efficacious and induce high levels of neutralizing antibody levels, the assumed mediators of protection. However, a correlate of protection against HPV is lacking, and the evidence is still limited as to long-term persistence of antibodies, especially following reduced dosing schedules. The World Health Organization (WHO) urges immunization of young girls as part of the strategy to eliminate cervical cancer, thus long-lasting protection is required. The current review describes longterm follow-up regarding vaccine-induced seropositivity and antibody level development following the different vaccines and dosing schedules. Implications and opportunities of long-term vaccine-induced immune responses are discussed, such as the gaps in monitoring of long-term immunogenicity, the possibilities of reduced dosing schedules, and the importance of evidence for durable immunity.
Background
In the Netherlands, the bivalent HPV vaccine (2vHPV) has been offered to preadolescent girls via the National Immunization Program (NIP) in a two-dose (2D) schedule since 2014. The current study estimates vaccine effectiveness (VE) against HPV infections up to four years post-vaccination among girls eligible for routine 2D immunization.
Methods
A cohort study (HAVANA2) was used in which participants annually filled out an online questionnaire and provided a vaginal self-sample for determination of HPV by the SPF10-LiPA25 assay, able to detect 25 HPV types. VE against incident type-specific infections and pooled outcomes was estimated by a Cox proportional hazards model with shared frailty between the HPV types.
Results
In total, 2027 girls were included in the study, 1098 (54.2%) of whom were vaccinated with two doses. Highest incidence rate was 5.0/1000 person-years (HPV51) among vaccinated participants and 9.1/1000 person-years (HPV74) among unvaccinated participants. Adjusted pooled VE was 84.0% (95%CI, 27.0-96.5%) against incident HPV16/18 infections and 86.5% (95%CI, 39.5-97.08%) against cross-protective types HPV31/33/45.
Conclusion
Four years post-vaccination, two doses of 2vHPV vaccination were effective in the prevention of incident HPV16/18 infections and provided cross-protection to HPV31/33/45. Our VE estimates rival those from three-dose schedules, indicating comparable protection by 2D schedules.
Background
In the Netherlands, the HPV-vaccine uptake was 52% during the 2009 catch-up campaign (birth cohorts 1993–1996). This increased to 61% in the regular immunization program (birth cohorts 2000–2001). However for birth cohorts 2003–2004 the uptake declined to 45.5%. With this study we aimed to gain insight into social, economic and cultural determinants that are associated with HPV-vaccination uptake and which subgroups with a lower HPV-vaccination uptake can be identified. In addition, we investigated whether the influence of these factors changed over time.
Methods
To study the determinants of HPV-vaccine uptake we performed a database study using different aggregation levels, i.e. individual level, postal code level and municipality level. All Dutch girls who were invited for HPV-vaccination through the National Immunization Program in the years 2012, 2014 and 2017 (i.e. birth cohorts 1999, 2001 and 2004, respectively) were included in the study population. We conducted multilevel logistic regression analyses to analyze the influence of the determinants on HPV-vaccination uptake, taking into account that the delivery of HPV-vaccine was nested within municipalities.
Results
Results showed that in particular having not received a MMR-vaccination, having one or two parents born in Morocco or Turkey, living in an area with lower socioeconomic status and higher municipal voting proportions for Christian political parties or populist parties with liberal-conservative views were associated with a lower HPV-vaccination uptake. Besides some changes in political preferences of the population and changes in the association between HPV uptake and urbanization level we found no clear determinants which could possibly explain the decrease in the HPV-vaccination uptake.
Conclusions
In this study we identified current social, economic and cultural determinants that are associated with HPV-vaccination uptake and which low-vaccination subgroups can be identified. However, no clear determinants were found which could explain the decrease in the HPV-vaccination uptake. Tailored information and/or consultation for groups that are associated with a lower HPV-vaccination uptake might help to increase the HPV-vaccination uptake in the future.
GMCs for HPV-16/18 were not noninferior for 2 versus 3 doses, except for HPV-18 (at 2-3 years after first dose). However, antibody avidity for these types showed noninferiority, independent of concentrations.
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