VP22 enhances antibody responses from DNA vaccines but not by intercellular spread

In some species DNA vaccines elicit potent humoral and cellular immune responses. However, their performance in humans and non-human primates is less impressive. There are suggestions in the literature that an increase in the intercellular distribution of protein expressed from a DNA vaccine may enh...

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Veröffentlicht in:Vaccine 2005-03, Vol.23 (16), p.1931-1940
Hauptverfasser: Perkins, Stuart D., Hartley, M. Gill, Lukaszewski, Roman A., Phillpotts, Robert J., Stevenson, Freda K., Bennett, Alice M.
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container_end_page 1940
container_issue 16
container_start_page 1931
container_title Vaccine
container_volume 23
creator Perkins, Stuart D.
Hartley, M. Gill
Lukaszewski, Roman A.
Phillpotts, Robert J.
Stevenson, Freda K.
Bennett, Alice M.
description In some species DNA vaccines elicit potent humoral and cellular immune responses. However, their performance in humans and non-human primates is less impressive. There are suggestions in the literature that an increase in the intercellular distribution of protein expressed from a DNA vaccine may enhance immunogenicity. We incorporated the Herpes Simplex Virus type 1 (HSV) VP22 gene, which encodes a protein that has been described as promoting intercellular spread, into a DNA vector in which it was fused to enhanced green fluorescent protein (EGFP). Following transfection of the plasmid DNA into mammalian cells, distribution of the fusion protein VP22-EGFP was not increased compared to EGFP alone. Furthermore, we found no evidence to suggest that VP22 was capable of mediating intercellular spread. However, when these constructs were used as DNA vaccines to immunise mice, antibody levels specific to EGFP were significantly enhanced when EGFP was fused to VP22. These data suggest that amplification of the immune response may occur via mechanisms other than VP22-mediated intercellular spread of antigen.
doi_str_mv 10.1016/j.vaccine.2004.10.033
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Gill ; Lukaszewski, Roman A. ; Phillpotts, Robert J. ; Stevenson, Freda K. ; Bennett, Alice M.</creator><creatorcontrib>Perkins, Stuart D. ; Hartley, M. Gill ; Lukaszewski, Roman A. ; Phillpotts, Robert J. ; Stevenson, Freda K. ; Bennett, Alice M.</creatorcontrib><description>In some species DNA vaccines elicit potent humoral and cellular immune responses. However, their performance in humans and non-human primates is less impressive. There are suggestions in the literature that an increase in the intercellular distribution of protein expressed from a DNA vaccine may enhance immunogenicity. We incorporated the Herpes Simplex Virus type 1 (HSV) VP22 gene, which encodes a protein that has been described as promoting intercellular spread, into a DNA vector in which it was fused to enhanced green fluorescent protein (EGFP). Following transfection of the plasmid DNA into mammalian cells, distribution of the fusion protein VP22-EGFP was not increased compared to EGFP alone. Furthermore, we found no evidence to suggest that VP22 was capable of mediating intercellular spread. However, when these constructs were used as DNA vaccines to immunise mice, antibody levels specific to EGFP were significantly enhanced when EGFP was fused to VP22. These data suggest that amplification of the immune response may occur via mechanisms other than VP22-mediated intercellular spread of antigen.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2004.10.033</identifier><identifier>PMID: 15734065</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Adjuvants, Immunologic ; Amino acids ; Animals ; Antibody Formation - drug effects ; Antigens ; Applied microbiology ; Biological and medical sciences ; Blotting, Western ; Cercopithecus aethiops ; COS Cells ; Deoxyribonucleic acid ; DNA ; DNA vaccine ; Fundamental and applied biological sciences. 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These data suggest that amplification of the immune response may occur via mechanisms other than VP22-mediated intercellular spread of antigen.</description><subject>Adjuvants, Immunologic</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Antibody Formation - drug effects</subject><subject>Antigens</subject><subject>Applied microbiology</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cercopithecus aethiops</subject><subject>COS Cells</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA vaccine</subject><subject>Fundamental and applied biological sciences. 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subjects Adjuvants, Immunologic
Amino acids
Animals
Antibody Formation - drug effects
Antigens
Applied microbiology
Biological and medical sciences
Blotting, Western
Cercopithecus aethiops
COS Cells
Deoxyribonucleic acid
DNA
DNA vaccine
Fundamental and applied biological sciences. Psychology
GFP
Green Fluorescent Proteins - immunology
Herpes simplex virus 1
Immune response
Immunization
Immunogenicity
Intercellular spread
Kinases
Laboratories
Methanol
Mice
Mice, Inbred BALB C
Microbiology
Plasmids - immunology
Primates
Protein transduction domain
Proteins
Studies
Tissue Fixation
Transfection
Tumors
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Vaccines, DNA - immunology
Viral Fusion Proteins - pharmacology
Viral Structural Proteins - pharmacology
VP22
title VP22 enhances antibody responses from DNA vaccines but not by intercellular spread
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