Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax
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 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 (PA63).
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 PA63 and the DNA vaccines expressing fusion proteins of PA63 with VP22.
Conclusion:
VP22 fusion does not improve the protection of A/J mice against live spore challenge following immunisation of DNA vaccines expressing PA63.
Perkins, Stuart D.
488070a7-a460-48a7-8ae5-bd3f3d195226
Flick-Smith, Helen C.
fee4da3f-bd48-4e85-803f-9589fa942964
Garmory, Helen S.
ccf884a2-a30a-417e-b769-dfa130656380
Essex-Lopresti, Angela E.
c2309a6b-5bf7-44b3-bd53-d48181d5ea52
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Phillpotts, Robert J.
a39782ff-2696-48de-8cf5-08fe6b6578c8
2005
Perkins, Stuart D.
488070a7-a460-48a7-8ae5-bd3f3d195226
Flick-Smith, Helen C.
fee4da3f-bd48-4e85-803f-9589fa942964
Garmory, Helen S.
ccf884a2-a30a-417e-b769-dfa130656380
Essex-Lopresti, Angela E.
c2309a6b-5bf7-44b3-bd53-d48181d5ea52
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Phillpotts, Robert J.
a39782ff-2696-48de-8cf5-08fe6b6578c8
Perkins, Stuart D., Flick-Smith, Helen C., Garmory, Helen S., Essex-Lopresti, Angela E., Stevenson, Freda K. and Phillpotts, Robert J.
(2005)
Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax.
Genetic Vaccines and Therapy, 3 (1).
(doi:10.1186/1479-0556-3-3).
Abstract
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 (PA63).
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 PA63 and the DNA vaccines expressing fusion proteins of PA63 with VP22.
Conclusion:
VP22 fusion does not improve the protection of A/J mice against live spore challenge following immunisation of DNA vaccines expressing PA63.
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Published date: 2005
Identifiers
Local EPrints ID: 26519
URI: http://eprints.soton.ac.uk/id/eprint/26519
ISSN: 1479-0556
PURE UUID: f7cee06e-d1c3-4463-958a-25b565c3b919
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Date deposited: 10 Apr 2006
Last modified: 16 Mar 2024 02:54
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Contributors
Author:
Stuart D. Perkins
Author:
Helen C. Flick-Smith
Author:
Helen S. Garmory
Author:
Angela E. Essex-Lopresti
Author:
Robert J. Phillpotts
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