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 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.
Perkins
Stuart D
SD
Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 OJQ, UK. sdperkins@dstl.gov.uk
Hartley
M Gill
MG
Lukaszewski
Roman A
RA
Phillpotts
Robert J
RJ
Stevenson
Freda K
FK
Bennett
Alice M
AM
D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D049452:Green Fluorescent Proteins / Q000276:immunology; D000432:Methanol; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000276:immunology; D016707:Tissue Fixation; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000494:pharmacology; D015678:Viral Structural Proteins / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D019444:Vaccines, DNA; D014760:Viral Fusion Proteins; D015678:Viral Structural Proteins; C485184:enhanced green fluorescent protein; C073413:herpes simplex virus type 1 protein VP22; D049452:Green Fluorescent Proteins; D000432:Methanol