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Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax

BACKGROUND: Previously, antigens expressed from DNA vaccines have been fused to the VP22 protein from Herpes Simplex Virus type I in order to improve efficacy. However, the immune enhancing mechanism of VP22 is poorly understood and initial suggestions that VP22 can mediate intercellular spread have...

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Autores principales: Perkins, Stuart D, Flick-Smith, Helen C, Garmory, Helen S, Essex-Lopresti, Angela E, Stevenson, Freda K, Phillpotts, Robert J
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1087864/
https://www.ncbi.nlm.nih.gov/pubmed/15842732
http://dx.doi.org/10.1186/1479-0556-3-3
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author Perkins, Stuart D
Flick-Smith, Helen C
Garmory, Helen S
Essex-Lopresti, Angela E
Stevenson, Freda K
Phillpotts, Robert J
author_facet Perkins, Stuart D
Flick-Smith, Helen C
Garmory, Helen S
Essex-Lopresti, Angela E
Stevenson, Freda K
Phillpotts, Robert J
author_sort Perkins, Stuart D
collection PubMed
description BACKGROUND: Previously, antigens expressed from DNA vaccines have been fused to the VP22 protein from Herpes Simplex Virus type I in order to improve efficacy. However, the immune enhancing mechanism of VP22 is poorly understood and initial suggestions that VP22 can mediate intercellular spread have been questioned. Despite this, fusion of VP22 to antigens expressed from DNA vaccines has improved immune responses, particularly to non-secreted antigens. METHODS: In this study, we fused the gene for the VP22 protein to the gene for Protective Antigen (PA) from Bacillus anthracis, the causative agent of anthrax. Protective immunity against infection with B. anthracis is almost entirely based on a response to PA and we have generated two constructs, where VP22 is fused to either the N- or the C-terminus of the 63 kDa protease-cleaved fragment of PA (PA(63)). RESULTS: Following gene gun immunisation of A/J mice with these constructs, we observed no improvement in the anti-PA antibody response generated. Following an intraperitoneal challenge with 70 50% lethal doses of B. anthracis strain STI spores, no difference in protection was evident in groups immunised with the DNA vaccine expressing PA(63 )and the DNA vaccines expressing fusion proteins of PA(63 )with VP22. CONCLUSION: VP22 fusion does not improve the protection of A/J mice against live spore challenge following immunisation of DNA vaccines expressing PA(63).
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spelling pubmed-10878642005-04-30 Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax Perkins, Stuart D Flick-Smith, Helen C Garmory, Helen S Essex-Lopresti, Angela E Stevenson, Freda K Phillpotts, Robert J Genet Vaccines Ther Research BACKGROUND: Previously, antigens expressed from DNA vaccines have been fused to the VP22 protein from Herpes Simplex Virus type I in order to improve efficacy. However, the immune enhancing mechanism of VP22 is poorly understood and initial suggestions that VP22 can mediate intercellular spread have been questioned. Despite this, fusion of VP22 to antigens expressed from DNA vaccines has improved immune responses, particularly to non-secreted antigens. METHODS: In this study, we fused the gene for the VP22 protein to the gene for Protective Antigen (PA) from Bacillus anthracis, the causative agent of anthrax. Protective immunity against infection with B. anthracis is almost entirely based on a response to PA and we have generated two constructs, where VP22 is fused to either the N- or the C-terminus of the 63 kDa protease-cleaved fragment of PA (PA(63)). RESULTS: Following gene gun immunisation of A/J mice with these constructs, we observed no improvement in the anti-PA antibody response generated. Following an intraperitoneal challenge with 70 50% lethal doses of B. anthracis strain STI spores, no difference in protection was evident in groups immunised with the DNA vaccine expressing PA(63 )and the DNA vaccines expressing fusion proteins of PA(63 )with VP22. CONCLUSION: VP22 fusion does not improve the protection of A/J mice against live spore challenge following immunisation of DNA vaccines expressing PA(63). BioMed Central 2005-04-20 /pmc/articles/PMC1087864/ /pubmed/15842732 http://dx.doi.org/10.1186/1479-0556-3-3 Text en Copyright © 2005 Perkins et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Perkins, Stuart D
Flick-Smith, Helen C
Garmory, Helen S
Essex-Lopresti, Angela E
Stevenson, Freda K
Phillpotts, Robert J
Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax
title Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax
title_full Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax
title_fullStr Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax
title_full_unstemmed Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax
title_short Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax
title_sort evaluation of the vp22 protein for enhancement of a dna vaccine against anthrax
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1087864/
https://www.ncbi.nlm.nih.gov/pubmed/15842732
http://dx.doi.org/10.1186/1479-0556-3-3
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