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Vaccination with human papillomavirus pseudovirus-encapsidated plasmids targeted to skin using microneedles.

ABSTRACT: Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.

SUBMITTER: Kines RC

PROVIDER: S-EPMC4364728 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Vaccination with human papillomavirus pseudovirus-encapsidated plasmids targeted to skin using microneedles.

Kines Rhonda C RC Zarnitsyn Vladimir V Johnson Teresa R TR Pang Yuk-Ying S YY Corbett Kizzmekia S KS Nicewonger John D JD Gangopadhyay Anu A Chen Man M Liu Jie J Prausnitz Mark R MR Schiller John T JT Graham Barney S BS

PloS one 20150318 3

Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 V ...[more]

PMID: 25785935

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Project description:BackgroundClaims of non-live vaccines having deleterious effects on non-targeted infectious disease and mortality among females persists. The majority of the available evidence is from West Africa and consists of observational studies and the interpretation and implications are controversial. Results from high-income countries have been conflicting. We evaluated the association between a human papillomavirus vaccine, a non-live vaccine primarily administered to pre-adolescent females, and non-targeted infectious disease in a high-income country.MethodsWe constructed a nationwide cohort of all Danish females 10 to 29 years of age during 2007 to 2016 with information on quadrivalent human papillomavirus vaccination status and infectious disease hospital contacts using national registers. Nested in this cohort, we conducted a self-controlled case series (SCCS) analysis comparing the rates of hospitalisation in a 90-day main risk period following the latest vaccination to reference period rates with adjustment for age and season.FindingsWe included 853,879 Danish-born females aged 10 to 29 years of age during the 2007 to 2016 study period in the study cohort. We identified a total of 65,293 infectious disease hospitalisations among 50,599 participants; 46,955 cases among 37,003 participants vaccinated during follow-up were included in the SCCS analysis. There was no statistically significantly increased risk of infectious disease hospitalisation in the 90-day main risk period (rate ratio 0.92, 95% CI 0.88 to 0.95).InterpretationReassuringly, our large well-controlled study does not support that human papillomavirus vaccination increases the risk of non-targeted infectious disease in any clinically meaningful way. While our study does not provide evidence against adverse effects of other non-live vaccines, it does provide evidence against the claim that all non-live vaccines increase risk of heterologous infections in females.FundingThe study was supported by the Novo Nordisk Foundation.

Dataset Information

Vaccination with human papillomavirus pseudovirus-encapsidated plasmids targeted to skin using microneedles.

Publications

Vaccination with human papillomavirus pseudovirus-encapsidated plasmids targeted to skin using microneedles.

Similar Datasets

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