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Development of AAVLP(HPV16/31L2) Particles as Broadly Protective HPV Vaccine Candidate
The human papillomavirus (HPV) minor capsid protein L2 is a promising candidate for a broadly protective HPV vaccine yet the titers obtained in most experimental systems are rather low. Here we examine the potential of empty AAV2 particles (AAVLPs), assembled from VP3 alone, for display of L2 epitop...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384601/ https://www.ncbi.nlm.nih.gov/pubmed/22761884 http://dx.doi.org/10.1371/journal.pone.0039741 |
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author | Nieto, Karen Weghofer, Margit Sehr, Peter Ritter, Mirko Sedlmeier, Sebastian Karanam, Balasubramanyam Seitz, Hanna Müller, Martin Kellner, Markus Hörer, Markus Michaelis, Uwe Roden, Richard B. S. Gissmann, Lutz Kleinschmidt, Jürgen A. |
author_facet | Nieto, Karen Weghofer, Margit Sehr, Peter Ritter, Mirko Sedlmeier, Sebastian Karanam, Balasubramanyam Seitz, Hanna Müller, Martin Kellner, Markus Hörer, Markus Michaelis, Uwe Roden, Richard B. S. Gissmann, Lutz Kleinschmidt, Jürgen A. |
author_sort | Nieto, Karen |
collection | PubMed |
description | The human papillomavirus (HPV) minor capsid protein L2 is a promising candidate for a broadly protective HPV vaccine yet the titers obtained in most experimental systems are rather low. Here we examine the potential of empty AAV2 particles (AAVLPs), assembled from VP3 alone, for display of L2 epitopes to enhance their immunogenicity. Insertion of a neutralizing epitope (amino acids 17–36) from L2 of HPV16 and HPV31 into VP3 at positions 587 and 453, respectively, permitted assembly into empty AAV particles (AAVLP(HPV16/31L2)). Intramuscularly vaccination of mice and rabbits with AAVLP(HPV16/31L2)s in montanide adjuvant, induced high titers of HPV16 L2 antibodies as measured by ELISA. Sera obtained from animals vaccinated with the AAVLP(HPV16/31L2)s neutralized infections with several HPV types in a pseudovirion infection assay. Lyophilized AAVLP(HPV16/31L2) particles retained their immunogenicity upon reconstitution. Interestingly, vaccination of animals that were pre-immunized with AAV2 - simulating the high prevalence of AAV2 antibodies in the population - even increased cross neutralization against HPV31, 45 and 58 types. Finally, passive transfer of rabbit antisera directed against AAVLP(HPV16/31L2)s protected naïve mice from vaginal challenge with HPV16 pseudovirions. In conclusion, AAVLP(HPV16/31L2) particles have the potential as a broadly protective vaccine candidate regardless of prior exposure to AAV. |
format | Online Article Text |
id | pubmed-3384601 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33846012012-07-03 Development of AAVLP(HPV16/31L2) Particles as Broadly Protective HPV Vaccine Candidate Nieto, Karen Weghofer, Margit Sehr, Peter Ritter, Mirko Sedlmeier, Sebastian Karanam, Balasubramanyam Seitz, Hanna Müller, Martin Kellner, Markus Hörer, Markus Michaelis, Uwe Roden, Richard B. S. Gissmann, Lutz Kleinschmidt, Jürgen A. PLoS One Research Article The human papillomavirus (HPV) minor capsid protein L2 is a promising candidate for a broadly protective HPV vaccine yet the titers obtained in most experimental systems are rather low. Here we examine the potential of empty AAV2 particles (AAVLPs), assembled from VP3 alone, for display of L2 epitopes to enhance their immunogenicity. Insertion of a neutralizing epitope (amino acids 17–36) from L2 of HPV16 and HPV31 into VP3 at positions 587 and 453, respectively, permitted assembly into empty AAV particles (AAVLP(HPV16/31L2)). Intramuscularly vaccination of mice and rabbits with AAVLP(HPV16/31L2)s in montanide adjuvant, induced high titers of HPV16 L2 antibodies as measured by ELISA. Sera obtained from animals vaccinated with the AAVLP(HPV16/31L2)s neutralized infections with several HPV types in a pseudovirion infection assay. Lyophilized AAVLP(HPV16/31L2) particles retained their immunogenicity upon reconstitution. Interestingly, vaccination of animals that were pre-immunized with AAV2 - simulating the high prevalence of AAV2 antibodies in the population - even increased cross neutralization against HPV31, 45 and 58 types. Finally, passive transfer of rabbit antisera directed against AAVLP(HPV16/31L2)s protected naïve mice from vaginal challenge with HPV16 pseudovirions. In conclusion, AAVLP(HPV16/31L2) particles have the potential as a broadly protective vaccine candidate regardless of prior exposure to AAV. Public Library of Science 2012-06-27 /pmc/articles/PMC3384601/ /pubmed/22761884 http://dx.doi.org/10.1371/journal.pone.0039741 Text en Nieto et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Nieto, Karen Weghofer, Margit Sehr, Peter Ritter, Mirko Sedlmeier, Sebastian Karanam, Balasubramanyam Seitz, Hanna Müller, Martin Kellner, Markus Hörer, Markus Michaelis, Uwe Roden, Richard B. S. Gissmann, Lutz Kleinschmidt, Jürgen A. Development of AAVLP(HPV16/31L2) Particles as Broadly Protective HPV Vaccine Candidate |
title | Development of AAVLP(HPV16/31L2) Particles as Broadly Protective HPV Vaccine Candidate |
title_full | Development of AAVLP(HPV16/31L2) Particles as Broadly Protective HPV Vaccine Candidate |
title_fullStr | Development of AAVLP(HPV16/31L2) Particles as Broadly Protective HPV Vaccine Candidate |
title_full_unstemmed | Development of AAVLP(HPV16/31L2) Particles as Broadly Protective HPV Vaccine Candidate |
title_short | Development of AAVLP(HPV16/31L2) Particles as Broadly Protective HPV Vaccine Candidate |
title_sort | development of aavlp(hpv16/31l2) particles as broadly protective hpv vaccine candidate |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384601/ https://www.ncbi.nlm.nih.gov/pubmed/22761884 http://dx.doi.org/10.1371/journal.pone.0039741 |
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