title: 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.
authors.affiliation: Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Rhonda C
authors.initials: RC
authors.lastname: Kines
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zarnitsyn
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Teresa R
authors.initials: TR
authors.lastname: Johnson
authors.affiliation: Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Yuk-Ying S
authors.initials: YY
authors.lastname: Pang
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Kizzmekia S
authors.initials: KS
authors.lastname: Corbett
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Nicewonger
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Anu
authors.initials: A
authors.lastname: Gangopadhyay
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Man
authors.initials: M
authors.lastname: Chen
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
authors.affiliation: Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000276:immunology; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D052162:Human papillomavirus 16 / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008845:Microinjections; D009339:Needles; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology*; D019076:Transgenes; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014760:Viral Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004279:DNA, Viral; D053918:Papillomavirus Vaccines; D058425:Vaccines, Virus-Like Particle; D014760:Viral Fusion Proteins; D014763:Viral Matrix Proteins; D008156:Luciferases