This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This NIH R01 project was awarded in 2008-2009 and was derived from an NIH R21 award entitled;""""""""Validating vIL-6 as a target for KSHV associated disease"""""""", which was an exploratory grant to investigate whether vIL-6 is necessary for RRV-associated disease. The focus of this research project is to investigate whether vaccination of RM with a novel vIL-6-Fc fusion protein is capable of inducing an immune response to inhibit the biological activity of viral IL-6. Analysis of animals vaccinated with the vIL-6-Fc fusion versus control animals given adjuvant alone indicates that vaccinated animals have a robust humoral response to RRV vIL-6. Second, a group of the vaccinated animals that was challenged with wild-type RRV have remained free of RRV-associated disease, despite evidence of virus infection. And finally, animals challenged with a recombinant RRV lacking the vIL-6 open reading frame and followed for virus infection and disease, were found to be free of RRV-associated disease. We have characterized the animals'immune responses to vIL-6 and have found that they possess neutralizing antibodies and T cell responses specific to vIL-6. We believe vaccination with vIL-6-Fc provides a novel and unique approach to inhibiting gamma-herpesvirus-associated disease
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