Xenotropic Murine Leukemia Virus-related Virus Vaccine
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Xenotropic murine leukemia virus-related virus (XMRV) is the first retrovirus identified in human tissue bearing adenocarcinoma of prostate. XMRV belongs to the virus family Retroviridae and the genus gammaretrovirus and has a single-stranded RNA genome that replicates through a DNA intermediate. It is a γ retrovirus that has been associated with chronic fatigue syndrome (CFS) and prostate cancer, and is closely related to a group of retroviruses called murine leukemia viruses (MLVs). CFS is a debilitating and complex illness characterized by profound fatigue, cognitive dysfunction, sleep abnormalities, autonomic manifestations, pain, and other symptoms exacerbated by exertion of any sort that is not improved by bed rest and that may be worsened by physical or mental activity.
Subunit XMRV Vaccines
A combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP) that had the size and morphology of live infectious XMRV was vaccinated to mice. Vaccine-induced XMRV env antibody titers were transiently high. The relatively rapid diminution in antibody levels may in part explain the differing prevalences reported for XMRV in various prostate cancer and chronic fatigue syndrome cohorts. This result preliminarily confirmed the effective ability of env-mediated immunosuppression (IS) in immunity, when expressed by allogeneic tumor cells normally rejected by engrafted mice, to allow these cells to escape, at least transiently, immune rejection. Using this approach, the key residues can be identified whose mutation specifically abolishes IS activity without affecting the “mechanical” fusogenic function of the entire envelope.
Therefore, “switched off’ the envelope-mediated immunosuppression of an infectious retrovirus genetically allows us to test the functional importance of envelope-mediated immunosuppression in retrovirus physiology. Remarkably, the non-IS mutant virus displays the same propagation kinetics as its WT counterpart in irradiated immunocompromised mice but it is rapidly and totally cleared from normal immunocompetent mice, which become fully protected against a challenge with the WT retrovirus. Using cell depletion strategies, scientists further establish that envelope-mediated immunosuppression enables the retrovirus to escape innate (natural killer cells) and adaptive (CD8+ T cells) antiviral effectors. Finally, the results show that inactivated mutant virions induce higher humoral and cellular responses than their WT counterparts. In conclusion, it demonstrates the critical role of Env-induced immunosuppression for retrovirus propagation in vivo and identifies a unique definite target for antiretroviral therapies and vaccine strategies, also characterized in the XMRV retroviruses, opening unprecedented prospects for the treatment of retroviral diseases. These results indicate a very significant increase in B-cell responses following introduction of specific mutations in their identified immunosuppressive domain (ISD) associated with the inhibition of their IS activity, should augur well for the proposed vaccine strategy.
Creative Biolabs is a highly proactive, robust, and diversified company with a strong, scientifically-proven background of viral vaccine development. We have experts who are able to help you with the vaccine development against xenotropic murine leukemia virus-related virus. Our scientists are confident in offering the best services and products upon request!
All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.