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The route of inoculation determines the tissue tropism of modified vaccinia Tiantan expressing the spike glycoprotein of SARS-CoV in mice.

Abstract
The 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.
AuthorsHuan Liu, Wenbo Yu, Xian Tang, Haibo Wang, Wenjie Ouyang, Jingying Zhou, Zhiwei Chen
JournalJournal of medical virology (J Med Virol) Vol. 82 Issue 5 Pg. 727-34 (May 2010) ISSN: 1096-9071 [Electronic] United States
PMID20336714 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright(c) 2010 Wiley-Liss, Inc.
Chemical References
  • Membrane Glycoproteins
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Attenuated
  • Viral Envelope Proteins
  • Viral Vaccines
Topics
  • Administration, Intranasal
  • Administration, Intravaginal
  • Animal Structures (pathology, virology)
  • Animals
  • Immunohistochemistry
  • In Situ Hybridization
  • Injections, Intramuscular
  • Membrane Glycoproteins (genetics)
  • Mice
  • Mice, Inbred BALB C
  • Polymerase Chain Reaction
  • SARS Virus (genetics)
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Attenuated (administration & dosage, adverse effects)
  • Vaccinia virus (genetics, physiology)
  • Viral Envelope Proteins (genetics)
  • Viral Tropism
  • Viral Vaccines (administration & dosage, adverse effects)

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