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Article: A single dose of oral DNA immunization delivered by attenuated Salmonella typhimurium down-regulates transgene expression in HBsAg transgenic mice

TitleA single dose of oral DNA immunization delivered by attenuated Salmonella typhimurium down-regulates transgene expression in HBsAg transgenic mice
Authors
KeywordsInhibition of HBV transgene
Oral DNA vaccination
T cell immunity
Issue Date2002
PublisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.eji.de
Citation
European Journal Of Immunology, 2002, v. 32 n. 11, p. 3294-3304 How to Cite?
AbstractThe efficacy of immunization with Salmonella typhimurium aroA to deliver the plasmid pRc/CMV-HBsAg (i.e. an oral DNA vaccine) was compared with that of intramuscular immunization with the same plasmid DNA, and with recombinant HBsAg protein, in a HBsAg transgenic mouse model. A single dose of oral DNA vaccine evoked vigorous Th1 cell and CTL responses and production of IgG2 subclass of anti-HBs after 2 weeks, and this was accompanied by a transient hepatitic flare with elevated alanine aminotransferase in the first 3 weeks. Concomitantly, the level of HBsAg-mRNA in liver tissues decreased by more than fourfold and viral-antigen expression was curtailed markedly in hepatocytes compared with controls. Hepatitic flare subsided after 3 weeks, but suppression of the transgene expression was continued in the absence of overt liver pathology for the remaining duration of the experiment (i.e. 12 weeks), and possibly beyond. The other vaccines could also break immune tolerance, but this was achieved only after repeated booster doses of the respective vaccines, and they did not affect transgene expression, or induce hepatic flare. We previously showed in non-transgenic mice that immunization by the oral DNA vaccine is achieved by an active intestinal infection with a bacterial carrier that is an adept intracellular parasite, and the immune response to the vaccination is orchestrated by phagocytic APC. Our present findings further implicated that the combined effects of an innate and a specific immune response induced by oral DNA vaccination are crucial in down-regulating HBsAg-transgene expression in hepatocytes.
Persistent Identifierhttp://hdl.handle.net/10722/78866
ISSN
2015 Impact Factor: 4.179
2015 SCImago Journal Rankings: 2.568
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZheng, BJen_HK
dc.contributor.authorNg, MHen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorTam, Sen_HK
dc.contributor.authorWoo, PCYen_HK
dc.contributor.authorNg, SPen_HK
dc.contributor.authorYuen, KYen_HK
dc.date.accessioned2010-09-06T07:47:46Z-
dc.date.available2010-09-06T07:47:46Z-
dc.date.issued2002en_HK
dc.identifier.citationEuropean Journal Of Immunology, 2002, v. 32 n. 11, p. 3294-3304en_HK
dc.identifier.issn0014-2980en_HK
dc.identifier.urihttp://hdl.handle.net/10722/78866-
dc.description.abstractThe efficacy of immunization with Salmonella typhimurium aroA to deliver the plasmid pRc/CMV-HBsAg (i.e. an oral DNA vaccine) was compared with that of intramuscular immunization with the same plasmid DNA, and with recombinant HBsAg protein, in a HBsAg transgenic mouse model. A single dose of oral DNA vaccine evoked vigorous Th1 cell and CTL responses and production of IgG2 subclass of anti-HBs after 2 weeks, and this was accompanied by a transient hepatitic flare with elevated alanine aminotransferase in the first 3 weeks. Concomitantly, the level of HBsAg-mRNA in liver tissues decreased by more than fourfold and viral-antigen expression was curtailed markedly in hepatocytes compared with controls. Hepatitic flare subsided after 3 weeks, but suppression of the transgene expression was continued in the absence of overt liver pathology for the remaining duration of the experiment (i.e. 12 weeks), and possibly beyond. The other vaccines could also break immune tolerance, but this was achieved only after repeated booster doses of the respective vaccines, and they did not affect transgene expression, or induce hepatic flare. We previously showed in non-transgenic mice that immunization by the oral DNA vaccine is achieved by an active intestinal infection with a bacterial carrier that is an adept intracellular parasite, and the immune response to the vaccination is orchestrated by phagocytic APC. Our present findings further implicated that the combined effects of an innate and a specific immune response induced by oral DNA vaccination are crucial in down-regulating HBsAg-transgene expression in hepatocytes.en_HK
dc.languageengen_HK
dc.publisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.eji.deen_HK
dc.relation.ispartofEuropean Journal of Immunologyen_HK
dc.subjectInhibition of HBV transgeneen_HK
dc.subjectOral DNA vaccinationen_HK
dc.subjectT cell immunityen_HK
dc.subject.meshAdministration, Oralen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshDown-Regulationen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGene Expression Regulationen_HK
dc.subject.meshHepatitis B Antibodies - biosynthesisen_HK
dc.subject.meshHepatitis B Surface Antigens - genetics - immunologyen_HK
dc.subject.meshHepatitis B Vaccines - administration & dosageen_HK
dc.subject.meshImmunizationen_HK
dc.subject.meshLiver - pathologyen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred BALB Cen_HK
dc.subject.meshMice, Inbred C57BLen_HK
dc.subject.meshMice, Transgenicen_HK
dc.subject.meshSalmonella typhimurium - geneticsen_HK
dc.subject.meshT-Lymphocytes, Cytotoxic - immunologyen_HK
dc.subject.meshTh1 Cells - immunologyen_HK
dc.subject.meshTranscription, Geneticen_HK
dc.subject.meshTransgenesen_HK
dc.subject.meshVaccines, DNA - immunologyen_HK
dc.titleA single dose of oral DNA immunization delivered by attenuated Salmonella typhimurium down-regulates transgene expression in HBsAg transgenic miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0014-2980&volume=32&issue=11&spage=3294&epage=3304&date=2002&atitle=A+single+dose+of+oral+DNA+immunization+delivered+by+attenuated+Salmonella+typhimurium+down-regulates+transgene+expression+in+HBsAg+transgenic+miceen_HK
dc.identifier.emailZheng, BJ:bzheng@hkucc.hku.hken_HK
dc.identifier.emailChan, KW:hrmtckw@hku.hken_HK
dc.identifier.emailWoo, PCY:pcywoo@hkucc.hku.hken_HK
dc.identifier.emailYuen, KY:kyyuen@hkucc.hku.hken_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityWoo, PCY=rp00430en_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/1521-4141(200211)32:11<3294::AID-IMMU3294>3.0.CO;2-Den_HK
dc.identifier.pmid12555675en_HK
dc.identifier.scopuseid_2-s2.0-0036856573en_HK
dc.identifier.hkuros88000en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036856573&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume32en_HK
dc.identifier.issue11en_HK
dc.identifier.spage3294en_HK
dc.identifier.epage3304en_HK
dc.identifier.isiWOS:000179276100030-
dc.publisher.placeGermanyen_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.scopusauthoridNg, MH=7202076421en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridTam, S=7202037323en_HK
dc.identifier.scopusauthoridWoo, PCY=7201801340en_HK
dc.identifier.scopusauthoridNg, SP=8862966400en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK

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