Abstract
BackgroundPreviously, 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.MethodsIn 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).ResultsFollowing 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.ConclusionVP22 fusion does not improve the protection of A/J mice against live spore challenge following immunisation of DNA vaccines expressing PA63.
Highlights
Antigens expressed from DNA vaccines have been fused to the VP22 protein from Herpes Simplex Virus type I in order to improve efficacy
P53 delivered by an adenovirus vector [5,6], GFP delivered by a lentivirus vector [7] and Human papillomavirus E7 antigen delivered by a Sindbis replicon [8,9] have all proved more effective after VP22 fusion
Cells transfected with the PA63-encoding DNA vaccine expressed a protein of approximately 68 kDa that reacted with Protective Antigen (PA)-specific antibody
Summary
Antigens expressed from DNA vaccines have been fused to the VP22 protein from Herpes Simplex Virus type I in order to improve efficacy. Fusion of VP22 to antigens expressed from DNA vaccines has improved immune responses, to non-secreted antigens. Composed of 301 amino acids, it has become known as a protein transduction domain able to mediate intercellular spread. VP22 has been reported as being able to exit the cell in which it is synthesised via an uncharacterised, golgi-independent secretory pathway and subsequently enter surrounding cells by a non-endocytic mechanism. These properties may be retained after fusion to other proteins [2]. P53 delivered by an adenovirus vector [5,6], GFP delivered by a lentivirus vector [7] and Human papillomavirus E7 antigen delivered by a Sindbis replicon [8,9] have all proved more effective after VP22 fusion
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
