Clinico-pathological study of schistosoma mansoni in olive baboons (papio cyanocephalus anubis) vaccinated with S. mansoni anti-oxidant enzymes and filamin encoding genes
Loading...
Date
2014-03-17
Authors
Omedo, Robin C. A.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Schistosomiasis is a parasitic disease caused by blood flukes of the genus
Schistosoma. It is second to malaria in importance and at present the most
effective control method is chemotherapy with use of praziquantel as the drug
of choice. With the rising cases of drug resistance and re-infection, the focus is
on development of a vaccine that can significantly reduce the incidence of the
disease. The ability of genes encoding S. mansoni CulZn superoxide dismutase
(CT-SOD) and glutathione peroxidase (GPX) to confer significant levels of
protective immunity in a murine model of S. mansoni have been demonstrated.
In addition to anti-oxidant enzymes, a gene encoding Sm- filamin has also
been shown to consistently induce a significant level of protection against
schistosomiasis in mice. In this study, therefore the aim was to determine
whether the protection observed in murine models can be replicated in the
olive baboons as no such work has been done in higher mammals. In the
study, animals in three groups were inoculated with 500J!g each of DNA
vaccines containing genes encoding S. mansoni CT-SOD, GPX and Smfilamin
respectively. The baboons in the fourth group received 500J!g each of
a vaccine containing a gene encoding GPX cloned in the reverse orientation
(XPG) and the animals in the fifth group were injected with normal saline
(0.85% NaCI). The animals were boosted at week 4, 8 and 12, and then rested
for 4 weeks. Thereafter, the animals were challenged with 800 S. mansoni
cercariae per animal percutaneously. The DNA vaccines did not alter the
blood parameters, indicating that they are safe for use in animal models. Genes
encoding S. mansoni anti-oxidant enzymes (CT-SOD and GPX) and Smfilamin
induced production of specific IgG against SEA, and the response to
SWAP was low, but this immune response was un-protective to baboons
against S. mansoni infection. The egg out-put was low in SOD, GPX and XPG
vaccinated baboons and highest in Sm-filamin vaccinated and normal saline
injected baboons. Worm burdens, gross and histo-hepato-intestinal pathology
including the mean hepatic egg-granuloma sizes in vaccinated and nonvaccinated
controls were statistically insignificant. Although the baboons
inoculated with Sm-pcGPX and Sm-pcXPG had a worm reduction of 7.47%
and 2.63% respectively, this was insignificant and below the WHO
requirement for vaccine. Those vaccinated with pcCT-SOD and Sm-filamin
had also insignificant worm reductions as compared to the controls. However,
all animals gained weight before inoculation, but lost weight after challenge
infection, with those vaccinated with SOD and GPX loosing less weight than
other groups and those vaccinated with XPG loosing more weight. Although,
these vaccines were able to induce immune responses to some worm antigens,
some of them (SOD and GPX) were able to cause less weight loss pi and also
low egg out put, but worm reduction and pathology in both vaccinated and
non-vaccinated were insignificant to indicate any protection. This study
recommends several things; these vaccines should be used with suitable
adjuvant in future studies, vaccines should also be combined into one
polyvalent vaccine, less weight loss and anti-fecundity effects of SOD and
GPX should also be further investigated. Genes encoding other schistosome
antigens that have shown protection in murine models should also be tested in
non-human primates as a prelude to human clinical trials.
Description
Department of Biochemistry and Biotechnology, 89p. The RA 644 .S3O4 2009
Keywords
Schistomiasis --Kenya --Prevention