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Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles

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 intravagina...

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Autores principales: Kines, Rhonda C., Zarnitsyn, Vladimir, Johnson, Teresa R., Pang, Yuk-Ying S., Corbett, Kizzmekia S., Nicewonger, John D., Gangopadhyay, Anu, Chen, Man, Liu, Jie, Prausnitz, Mark R., Schiller, John T., Graham, Barney S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364728/
https://www.ncbi.nlm.nih.gov/pubmed/25785935
http://dx.doi.org/10.1371/journal.pone.0120797
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author Kines, Rhonda C.
Zarnitsyn, Vladimir
Johnson, Teresa R.
Pang, Yuk-Ying S.
Corbett, Kizzmekia S.
Nicewonger, John D.
Gangopadhyay, Anu
Chen, Man
Liu, Jie
Prausnitz, Mark R.
Schiller, John T.
Graham, Barney S.
author_facet Kines, Rhonda C.
Zarnitsyn, Vladimir
Johnson, Teresa R.
Pang, Yuk-Ying S.
Corbett, Kizzmekia S.
Nicewonger, John D.
Gangopadhyay, Anu
Chen, Man
Liu, Jie
Prausnitz, Mark R.
Schiller, John T.
Graham, Barney S.
author_sort Kines, Rhonda C.
collection PubMed
description 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.
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spelling pubmed-43647282015-03-23 Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles Kines, Rhonda C. Zarnitsyn, Vladimir Johnson, Teresa R. Pang, Yuk-Ying S. Corbett, Kizzmekia S. Nicewonger, John D. Gangopadhyay, Anu Chen, Man Liu, Jie Prausnitz, Mark R. Schiller, John T. Graham, Barney S. PLoS One Research Article 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. Public Library of Science 2015-03-18 /pmc/articles/PMC4364728/ /pubmed/25785935 http://dx.doi.org/10.1371/journal.pone.0120797 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Kines, Rhonda C.
Zarnitsyn, Vladimir
Johnson, Teresa R.
Pang, Yuk-Ying S.
Corbett, Kizzmekia S.
Nicewonger, John D.
Gangopadhyay, Anu
Chen, Man
Liu, Jie
Prausnitz, Mark R.
Schiller, John T.
Graham, Barney S.
Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles
title Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles
title_full Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles
title_fullStr Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles
title_full_unstemmed Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles
title_short Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles
title_sort vaccination with human papillomavirus pseudovirus-encapsidated plasmids targeted to skin using microneedles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364728/
https://www.ncbi.nlm.nih.gov/pubmed/25785935
http://dx.doi.org/10.1371/journal.pone.0120797
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