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.