Dataset Information

Skin vaccination against cervical cancer associated human papillomavirus with a novel micro-projection array in a mouse model.

ABSTRACT:

Background

Better delivery systems are needed for routinely used vaccines, to improve vaccine uptake. Many vaccines contain alum or alum based adjuvants. Here we investigate a novel dry-coated densely-packed micro-projection array skin patch (Nanopatch™) as an alternate delivery system to intramuscular injection for delivering an alum adjuvanted human papillomavirus (HPV) vaccine (Gardasil®) commonly used as a prophylactic vaccine against cervical cancer.

Methodology/principal findings

Micro-projection arrays dry-coated with vaccine material (Gardasil®) delivered to C57BL/6 mouse ear skin released vaccine within 5 minutes. To assess vaccine immunogenicity, doses of corresponding to HPV-16 component of the vaccine between 0.43 ± 0.084 ng and 300 ± 120 ng (mean ± SD) were administered to mice at day 0 and day 14. A dose of 55 ± 6.0 ng delivered intracutaneously by micro-projection array was sufficient to produce a maximal virus neutralizing serum antibody response at day 28 post vaccination. Neutralizing antibody titres were sustained out to 16 weeks post vaccination, and, for comparable doses of vaccine, somewhat higher titres were observed with intracutaneous patch delivery than with intramuscular delivery with the needle and syringe at this time point.

Conclusions/significance

Use of dry micro-projection arrays (Nanopatch™) has the potential to overcome the need for a vaccine cold chain for common vaccines currently delivered by needle and syringe, and to reduce risk of needle-stick injury and vaccine avoidance due to the fear of the needle especially among children.

SUBMITTER: Corbett HJ

PROVIDER: S-EPMC2956639 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

Skin vaccination against cervical cancer associated human papillomavirus with a novel micro-projection array in a mouse model.

Corbett Holly J HJ Fernando Germain J P GJ Chen Xianfeng X Frazer Ian H IH Kendall Mark A F MA

PloS one 20101018 10

<h4>Background</h4>Better delivery systems are needed for routinely used vaccines, to improve vaccine uptake. Many vaccines contain alum or alum based adjuvants. Here we investigate a novel dry-coated densely-packed micro-projection array skin patch (Nanopatch™) as an alternate delivery system to intramuscular injection for delivering an alum adjuvanted human papillomavirus (HPV) vaccine (Gardasil®) commonly used as a prophylactic vaccine against cervical cancer.<h4>Methodology/principal finding ...[more]

PMID: 20976136

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Project description:Cervical cancer is the fourth most common cancer in women with an estimated 570,000 new cases in 2018 which constitute about 6. 6% of all cancers in women according to WHO report 2018. Approximately 90% of the 270,000 deaths from cervical cancer in 2015 occurred in low- and middle-income countries. In cervical cancers, which is caused by human papillomavirus (HPV) infection, the expression of HPV 16 E6 and E7 proteins are essential for tumor cell transformation and maintenance of malignancy. Prophylactic vaccines against cervical cancer caused by human papillomavirus have not proven successful. Although virus-like particle-based (VLPs) vaccines have been developed with prophylactic activities to prevent most HPV infections, the therapeutic effect of VLP vaccines has yet to be demonstrated for those who were already infected. A recent study showed that pre-conditioning mice with a potent antigen such as tetanus toxoid significantly improves lymph node homing and efficacy of dendritic cells. Tetanus toxoid has also been used in combination with DNA vaccines designed from tumor based antigens. In the present study, we pre-conditioned mice with tetanus toxoid followed by vaccination with a Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) overexpressing tumor-cell based vaccine (GVAX). We observed that pre-conditioning with tetanus toxoid followed by vaccination with GVAX regressed tumor growth and enhanced the overall survival of the mice. Pre-conditioning with tetanus toxoid enhanced the immune response which was observed by enlarged spleen size, higher proliferation rate of lymphocytes, a higher level of IFN-?, TNF-?, and IL-4 antigen-specific secretions by the splenocytes. Pre-conditioning with tetanus toxoid increased memory T cell migration into the tumor site and spleen. The antigen-specific cytotoxic T cell lysis percentage was also found to be higher in the group of mice vaccinated with the combination of tetanus toxoid and GVAX. Hence, pre-conditioning with tetanus toxoid prior to vaccination with a tumor-cell based vaccine overexpressing GM-CSF might be an effective strategy for targeting E7-specific HPV-associated cervical malignancy.

Project description:BackgroundVaccination against human papillomavirus (HPV), predominantly targeting young females, has been introduced in many countries. Decisions to implement programs, which have involved substantial investment by governments, have in part been based on findings from cost-effectiveness models. Now that vaccination programs have been in place for some years, it is becoming possible to observe their effects, and compare these with model effectiveness predictions made previously.FindingsAustralia introduced a publicly-funded HPV vaccination program in 2007. Recently reported Australian data from a repeat cross-sectional survey showed a substantial (77%) fall in HPV16 prevalence in women aged 18-24 years in 2010-2011, compared to pre-vaccination levels. We have previously published model predictions for the population-wide reduction in incident HPV16 infections post-vaccination in Australia. We compared prior predictions from the same model (including the same assumed uptake rates) for the reduction in HPV16 prevalence in women aged 18-24 years by the end of 2010 with the observed data. Based on modelled vaccine uptake which is consistent with recent data on three-dose uptake (78% at 12-13 years; lower uptake in older catch-up age cohorts), we had predicted a 70% reduction in prevalence in 18-24 year old females by the end of 2010. Based on modelled vaccine uptake consistent with recent national data for two-dose coverage and similar to that reported by women in the cross-sectional study, we had predicted a 79% reduction.ConclusionsA close correspondence was observed between the prior model predictions and the recently reported findings on the rapid drop in HPV prevalence in Australia. Because broadly similar effectiveness predictions have been reported from other models used for cost-effectiveness predictions, this provides reassurance that the substantial public investment in HPV vaccination has been grounded in valid estimates of the effects of vaccination.

Project description:ImportanceBarriers to childhood vaccination against vaccine-preventable diseases, such as those due to human papillomavirus (HPV), are well known. However, the role of salience bias-the change in perception of risk due to increased familiarity with the outcome-in decisions to vaccinate children has not been explicitly studied.ObjectiveTo assess for salience bias in parental decisions to vaccinate children.Design, setting, and participantsThis retrospective cohort study used a time-to-event (survival) analysis to compare vaccination rates of children whose mothers had a history of cervical cancer or a cervical biopsy, who have experienced adverse vaccine-preventable outcomes, and for whom vaccination may be more salient, with a control group of children whose mothers had no such history. Participants were accrued from the MarketScan Commercial Database, including US children who turned 11 years old, when HPV vaccination is recommended, from January 1, 2014, to December 31, 2018. Data were analyzed from December 29, 2020, to September 17, 2021.ExposuresMaternal history of cervical cancer or cervical biopsy.Main outcomes and measuresVaccination against HPV.ResultsA total of 757 428 children (370 878 girls [49.0%] and 386 550 boys [51.0%]) were identified, of whom 38 366 had mothers with a history of cervical biopsy alone and 1084 had mothers with a history of cervical cancer. Overall, 54.2% of children (55.7% of girls and 52.7% of boys) received at least 1 vaccination by 16 years of age. In a time-to-event analysis, HPV vaccination did not differ between children whose mothers had cervical cancer vs those whose mothers did not (hazard ratio [HR] for girls, 0.99 [95% CI, 0.86-1.13]; HR for boys, 1.08 [95% CI, 0.94-1.24]). Maternal history of cervical biopsy was associated with a minimally increased hazard of vaccination (HR for girls, 1.06 [95% CI, 1.04-1.09]; HR for boys, 1.04 [95% CI, 1.01-1.06]). There were no clinically meaningful differences between groups for the tetanus/diphtheria/acellular pertussis and meningococcal vaccinations, which are also recommended at 11 years of age.Conclusions and relevanceIn this analysis of salience bias in childhood vaccination decisions, mothers' personal history of cervical cancer or cervical biopsy was not associated with greater vaccination rates among children against HPV. These findings suggest that salience of vaccine-preventable outcomes may not have a major impact on childhood vaccine hesitancy in HPV; the role of salience should be investigated for other vaccines.

Dataset Information

Skin vaccination against cervical cancer associated human papillomavirus with a novel micro-projection array in a mouse model.

Background

Methodology/principal findings

Conclusions/significance

Publications

Skin vaccination against cervical cancer associated human papillomavirus with a novel micro-projection array in a mouse model.

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