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Immunization of mice by a multimeric L2-based linear epitope (17-36) from HPV type 16/18 induced cross reactive neutralizing antibodies

Current licensed and commercially available prophylactic human papillomavirus (HPV) vaccines (Cervarix and quadrivalent/nine valents Gardasil) are based on major capsid protein L1 virus-like particles (VLPs) production which are expensive and type specific. Minor capsid L2-RG1 linear epitope (17-36)...

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Autores principales: Khiavi, Farhad Motavalli, Arashkia, Arash, Nasimi, Maryam, Mahdavi, Mehdi, Golkar, Majid, Roohvand, Farzin, Azadmanesh, Kayhan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566000/
https://www.ncbi.nlm.nih.gov/pubmed/28855937
http://dx.doi.org/10.4103/1735-5362.212043
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author Khiavi, Farhad Motavalli
Arashkia, Arash
Nasimi, Maryam
Mahdavi, Mehdi
Golkar, Majid
Roohvand, Farzin
Azadmanesh, Kayhan
author_facet Khiavi, Farhad Motavalli
Arashkia, Arash
Nasimi, Maryam
Mahdavi, Mehdi
Golkar, Majid
Roohvand, Farzin
Azadmanesh, Kayhan
author_sort Khiavi, Farhad Motavalli
collection PubMed
description Current licensed and commercially available prophylactic human papillomavirus (HPV) vaccines (Cervarix and quadrivalent/nine valents Gardasil) are based on major capsid protein L1 virus-like particles (VLPs) production which are expensive and type specific. Minor capsid L2-RG1 linear epitope (17-36) is a known candidate for induction of cross-neutralizing antibodies to develop low-cost pan-HPV vaccines. Herein, we report construction and expression of a three tandem repeats of L2-RG1 derived from HPV16 and 18 fused with the same head to tail pattern (HPV16:17-36×3+ HPV18:17-36×3; hereafter termed dual-type fusion L2 peptide) in E. coli and provide the results of its immunogenicity in mice. SDS-PAGE and western blot analyses indicated proper expression of the peptide that could be further purified by Ni-NTA affinity chromatography via the located C-terminal 6xHis-tag. Mice immunized by formulation of the purified peptide and Freund adjuvant raised neutralizing antibodies which showed proper cross reactivity to HPV L2 (11-200) of types: 18, 16, 31 and 45 (which totally are responsible for 90% of cervical cancers) and efficiently neutralized HPV18/16 pseudoviruses in vitro. Our results imply the possibility of development of a simple, low-cost preventive HPV vaccine based on this dual-type fusion L2 peptide in bacterial expression system with broad spectrum.
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spelling pubmed-55660002017-08-30 Immunization of mice by a multimeric L2-based linear epitope (17-36) from HPV type 16/18 induced cross reactive neutralizing antibodies Khiavi, Farhad Motavalli Arashkia, Arash Nasimi, Maryam Mahdavi, Mehdi Golkar, Majid Roohvand, Farzin Azadmanesh, Kayhan Res Pharm Sci Original Article Current licensed and commercially available prophylactic human papillomavirus (HPV) vaccines (Cervarix and quadrivalent/nine valents Gardasil) are based on major capsid protein L1 virus-like particles (VLPs) production which are expensive and type specific. Minor capsid L2-RG1 linear epitope (17-36) is a known candidate for induction of cross-neutralizing antibodies to develop low-cost pan-HPV vaccines. Herein, we report construction and expression of a three tandem repeats of L2-RG1 derived from HPV16 and 18 fused with the same head to tail pattern (HPV16:17-36×3+ HPV18:17-36×3; hereafter termed dual-type fusion L2 peptide) in E. coli and provide the results of its immunogenicity in mice. SDS-PAGE and western blot analyses indicated proper expression of the peptide that could be further purified by Ni-NTA affinity chromatography via the located C-terminal 6xHis-tag. Mice immunized by formulation of the purified peptide and Freund adjuvant raised neutralizing antibodies which showed proper cross reactivity to HPV L2 (11-200) of types: 18, 16, 31 and 45 (which totally are responsible for 90% of cervical cancers) and efficiently neutralized HPV18/16 pseudoviruses in vitro. Our results imply the possibility of development of a simple, low-cost preventive HPV vaccine based on this dual-type fusion L2 peptide in bacterial expression system with broad spectrum. Medknow Publications & Media Pvt Ltd 2017-08 /pmc/articles/PMC5566000/ /pubmed/28855937 http://dx.doi.org/10.4103/1735-5362.212043 Text en Copyright: © 2017 Research in Pharmaceutical Sciences http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Original Article
Khiavi, Farhad Motavalli
Arashkia, Arash
Nasimi, Maryam
Mahdavi, Mehdi
Golkar, Majid
Roohvand, Farzin
Azadmanesh, Kayhan
Immunization of mice by a multimeric L2-based linear epitope (17-36) from HPV type 16/18 induced cross reactive neutralizing antibodies
title Immunization of mice by a multimeric L2-based linear epitope (17-36) from HPV type 16/18 induced cross reactive neutralizing antibodies
title_full Immunization of mice by a multimeric L2-based linear epitope (17-36) from HPV type 16/18 induced cross reactive neutralizing antibodies
title_fullStr Immunization of mice by a multimeric L2-based linear epitope (17-36) from HPV type 16/18 induced cross reactive neutralizing antibodies
title_full_unstemmed Immunization of mice by a multimeric L2-based linear epitope (17-36) from HPV type 16/18 induced cross reactive neutralizing antibodies
title_short Immunization of mice by a multimeric L2-based linear epitope (17-36) from HPV type 16/18 induced cross reactive neutralizing antibodies
title_sort immunization of mice by a multimeric l2-based linear epitope (17-36) from hpv type 16/18 induced cross reactive neutralizing antibodies
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566000/
https://www.ncbi.nlm.nih.gov/pubmed/28855937
http://dx.doi.org/10.4103/1735-5362.212043
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