Abstract:
:The natural site of infection for T. gondii is the mucosal surface of the intestine, so the protective immunity obtained after natural infection with T. gondii points to the importance of developing a vaccine that stimulates mucosal defences. In this study, an aroA- and aroD- attenuated strain of Salmonella typhimurium (BRD509) has been used to deliver the recombinant eukaryotic plasmid pSAG(1-2)/CTA2/B expressing a multi-antigenic gene encoding SAG1 and SAG2 of T. gondii linked to A2/B subunits of cholera toxin as a candidate oral T. gondii vaccine. Immunoblot analysis showed compound gene expression in HeLa cells in vitro and intragastric immunization of mice with the recombinant salmonella resulted in the induction of humoral and Th1 type cellular immune responses and afforded protection against RH strain T. gondii challenge. Anti-T. gondii IgG values increased markedly in the BRD509/pSAG(1-2)-CTA2/B immunized group; these values were significantly higher than those in the negative controls (P = 0.008). With CTA2/B genetic adjuvant, the T. gondii-specific response was predominantly Th1, indicating that the CTA(2)/B genetic adjuvant was able to overcome the strong Th2-bias of the antigen (IgG2a > IgG1). Antigen-specific T cell proliferative responses and CTL activity were significantly enhanced when cholera toxin CTA2/B genetic adjuvant was used (P = 0.009; P = 0.006). Culture supernatants from antigen-stimulated splenocytes from mice in these groups were also examined by ELISA for Th1- and Th2-type cytokines; mean IFN-gamma levels produced after oral immunization with BRD509/pSAG(1-2)-CTA2/B were about nine-fold higher than after immunization with BRD509/pSAG(1-2) (P = 0.007). On the other hand, the levels of IL-4 were low for all groups and no increase was seen in the presence of CTA2/B genetic adjuvant. When the immunized mice were intraperitoneally challenged with 10(3) tachyzoites of the highly virulent RH strain, the survival time of the mice immunized with BRD509/pSAG(1-2)-CTA2/B was markedly longer than other groups (P = 0.003) and a 40% survival rate was achieved. This is the first report that demonstrates that an oral attenuated salmonella DNA vaccine can induce protective immunity against the acute phase of T. gondii infection.
journal_name
Parasite Immunoljournal_title
Parasite immunologyauthors
Cong H,Gu QM,Jiang Y,He SY,Zhou HY,Yang TT,Li Y,Zhao QLdoi
10.1111/j.1365-3024.2005.00738.xkeywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
29-35issue
1-2eissn
0141-9838issn
1365-3024pii
PIM738journal_volume
27pub_type
杂志文章abstract::We have investigated whether a protective immune response occurred in mice infected with a virulent cloned strain of Plasmodium chabaudi. Animals inoculated intravenously with 10(7) parasitized erythrocytes (PE) showed an exponentially increasing parasitaemia and died by day 6 of the infection, presenting a pronounced...
journal_title:Parasite immunology
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journal_title:Parasite immunology
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journal_title:Parasite immunology
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journal_title:Parasite immunology
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journal_title:Parasite immunology
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journal_title:Parasite immunology
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journal_title:Parasite immunology
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journal_title:Parasite immunology
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journal_title:Parasite immunology
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journal_title:Parasite immunology
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journal_title:Parasite immunology
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journal_title:Parasite immunology
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journal_title:Parasite immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3024.1985.tb00091.x
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journal_title:Parasite immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3024.1983.tb00738.x
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journal_title:Parasite immunology
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journal_title:Parasite immunology
pub_type: 杂志文章,评审
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journal_title:Parasite immunology
pub_type: 杂志文章
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journal_title:Parasite immunology
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