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

Stuart D Perkins1 email, Helen C Flick-Smith1 email, Helen S Garmory1 email, Angela E Essex-Lopresti1 email, Freda K Stevenson2 email and Robert J Phillpotts1 email

Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 OJQ, UK

Tenovus Laboratory, University of Southampton Hospital NHS Trust, Southampton, SO16 6YD, UK

author email corresponding author email

Genetic Vaccines and Therapy 2005, 3:3doi:10.1186/1479-0556-3-3

Published: 20 April 2005

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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