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Article: The route of inoculation determines the tissue tropism of modified vaccinia tiantan expressing the spike glycoprotein of SARS-CoV in mice

TitleThe route of inoculation determines the tissue tropism of modified vaccinia tiantan expressing the spike glycoprotein of SARS-CoV in mice
Authors
KeywordsMVTT
Tissue tropism
Vaccination route
Vaccine
Vaccinia
Issue Date2010
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/32763
Citation
Journal Of Medical Virology, 2010, v. 82 n. 5, p. 727-734 How to Cite?
AbstractThe live replication-competent modified vaccinia virus Tiantan (MVTT) is an attractive vaccine vector, yet little is known about its tissue tropism and pathology in vivo. Recently, we demonstrated that a recombinant MVTT expressing the spike glycoprotein of SARS-CoV (namely MVTT-S) is superior to the non-replicating modified vaccinia Ankara (MVA-S) for inducing high level of neutralizing antibodies through mucosal vaccination. In this study, we further determined the tissue tropism and safety of MVTT-S after the vaccine was administrated through various routes including: intramuscular (i.m.), intranasal (i.n.), and intravaginal (i.vag.) inoculations, respectively. Using real-time PCR, nested PCR, immunohistochemistry and in situ hybridization assays, we found that MVTT-S was able to produce a transient infection in all cases within 48 hr post-inoculation, yet the major site of viral replication in various tissues or organs was dependent on the route of viral administration. We demonstrated that i.m. injection of MVTT-S primarily targeted draining inguinal lymph nodes, whereas mucosal inoculation had broader range of tissue infections. i.n. inoculation involved infections in lungs, kidneys, spleens and cervix lymph nodes while i.vag. administration targeted uteruses, ovaries, kidneys and spleens. Critically, the infection did not cause severe pathogenic consequences in infected tissues, which was consistent to the attenuated phenotype of MVTT-S. Our findings have implications for the optimization of vaccination route and for studies on the correlation between the magnitude of immune responses and the extent of tissue involvement in vivo. © 2010 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/130629
ISSN
2015 Impact Factor: 1.998
2015 SCImago Journal Rankings: 1.015
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant CouncilHK-RGC762208
HK-RGC762209
National Basic Research Program of China2006CB504208
National 11th 5-year Project2008ZX10001-011
University Development Fund of the University of Hong Kong
Funding Information:

Grant sponsor: Hong Kong Research Grant Council (to Z.C.); Grant numbers: HK-RGC762208, HK-RGC762209; Grant sponsor: National Basic Research Program of China (the 973 project); Grant number: 2006CB504208; Grant sponsor: National 11th 5-year Project; Grant number: 2008ZX10001-011; Grant sponsor: University Development Fund of the University of Hong Kong to its AIDS Institute.

References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Hen_HK
dc.contributor.authorYu, Wen_HK
dc.contributor.authorTang, Xen_HK
dc.contributor.authorWang, Hen_HK
dc.contributor.authorOuyang, Wen_HK
dc.contributor.authorZhou, Jen_HK
dc.contributor.authorChen, Zen_HK
dc.date.accessioned2010-12-23T10:31:27Z-
dc.date.available2010-12-23T10:31:27Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Medical Virology, 2010, v. 82 n. 5, p. 727-734en_HK
dc.identifier.issn0146-6615en_HK
dc.identifier.urihttp://hdl.handle.net/10722/130629-
dc.description.abstractThe live replication-competent modified vaccinia virus Tiantan (MVTT) is an attractive vaccine vector, yet little is known about its tissue tropism and pathology in vivo. Recently, we demonstrated that a recombinant MVTT expressing the spike glycoprotein of SARS-CoV (namely MVTT-S) is superior to the non-replicating modified vaccinia Ankara (MVA-S) for inducing high level of neutralizing antibodies through mucosal vaccination. In this study, we further determined the tissue tropism and safety of MVTT-S after the vaccine was administrated through various routes including: intramuscular (i.m.), intranasal (i.n.), and intravaginal (i.vag.) inoculations, respectively. Using real-time PCR, nested PCR, immunohistochemistry and in situ hybridization assays, we found that MVTT-S was able to produce a transient infection in all cases within 48 hr post-inoculation, yet the major site of viral replication in various tissues or organs was dependent on the route of viral administration. We demonstrated that i.m. injection of MVTT-S primarily targeted draining inguinal lymph nodes, whereas mucosal inoculation had broader range of tissue infections. i.n. inoculation involved infections in lungs, kidneys, spleens and cervix lymph nodes while i.vag. administration targeted uteruses, ovaries, kidneys and spleens. Critically, the infection did not cause severe pathogenic consequences in infected tissues, which was consistent to the attenuated phenotype of MVTT-S. Our findings have implications for the optimization of vaccination route and for studies on the correlation between the magnitude of immune responses and the extent of tissue involvement in vivo. © 2010 Wiley-Liss, Inc.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/32763en_HK
dc.relation.ispartofJournal of Medical Virologyen_HK
dc.rightsJournal of Medical Virology. Copyright © John Wiley & Sons, Inc.-
dc.subjectMVTTen_HK
dc.subjectTissue tropismen_HK
dc.subjectVaccination routeen_HK
dc.subjectVaccineen_HK
dc.subjectVacciniaen_HK
dc.subject.meshMembrane Glycoproteins - genetics-
dc.subject.meshSARS Virus - genetics-
dc.subject.meshVaccines, Attenuated - administration and dosage - adverse effects-
dc.subject.meshVaccinia virus - genetics - physiology-
dc.subject.meshViral Envelope Proteins - genetics-
dc.titleThe route of inoculation determines the tissue tropism of modified vaccinia tiantan expressing the spike glycoprotein of SARS-CoV in miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0146-6615&volume=82&issue=5&spage=727&epage=734&date=2010&atitle=The+route+of+inoculation+determines+the+tissue+tropism+of+modified+vaccinia+Tiantan+expressing+the+spike+glycoprotein+of+SARS-CoV+in+mice-
dc.identifier.emailChen, Z:zchenai@hkucc.hku.hken_HK
dc.identifier.authorityChen, Z=rp00243en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/jmv.21667en_HK
dc.identifier.pmid20336714-
dc.identifier.scopuseid_2-s2.0-77951017160en_HK
dc.identifier.hkuros176630en_US
dc.identifier.hkuros181676-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951017160&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume82en_HK
dc.identifier.issue5en_HK
dc.identifier.spage727en_HK
dc.identifier.epage734en_HK
dc.identifier.isiWOS:000276324100001-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLiu, H=15019354200en_HK
dc.identifier.scopusauthoridYu, W=50162901500en_HK
dc.identifier.scopusauthoridTang, X=36143652700en_HK
dc.identifier.scopusauthoridWang, H=8724886600en_HK
dc.identifier.scopusauthoridOuyang, W=36143383300en_HK
dc.identifier.scopusauthoridZhou, J=17344792400en_HK
dc.identifier.scopusauthoridChen, Z=35271180800en_HK

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