Dr. Drew et al., Humoral immune responses to DNA vaccines expressing secreted, membrane bound and non-secreted forms of the Taenia ovis 45W antigen, VACCINE, 18(23), 2000, pp. 2522-2532
The antibody response to DNA vaccines expressing secreted, membrane bound a
nd non-secreted forms of the same antigen was investigated. The antigen gen
e selected for these studies was the full length 45W antigen gene from Taen
ia ovis. This gene encodes a host protective membrane bound antigen with a
native secretion signal at the amino terminus and a hydrophobic anchor doma
in at the carboxyl terminus. Full length and rationally truncated forms of
the 45W antigen gene were generated and used to construct DNA vaccines enco
ding membrane bound, secreted and non-secreted forms of the 45W antigen. Th
e cellular localisation of these antigen forms was confirmed by Western blo
t studies. BALB/c mice were immunised intramuscularly with plasmid DNA and
serum antibody responses measured by enzyme linked immunosorbant assay (ELI
SA). The cellular localisation of DNA vaccine antigen had a significant eff
ect on the magnitude but not the subclass of antibody responses. Immunisati
on with DNA expressing secreted 45W generated three-fold higher antibody ti
tres than immunisation with DNA expressing membrane bound 45W, and 18-fold
higher antibody titres than DNA expressing non-secreted 45W. All mice gener
ated a predominantly IgG1 antibody response indicative of a TH-2 type immun
e response. These results indicate that the optimal induction of humoral im
mune responses to intramuscular genetic immunisation with the 45W antigen,
requires the active secretion of antigen. This observation may be of value
during the design of DNA vaccines in the future. (C) 2000 Published by Else
vier Science Ltd. All rights reserved.