Natalia Makarova1,2, Chunxia Zhao1,2, Yuanyuan Zhang1,2, Sushma Bhosle4, Suganthi Suppiah4, Jeanne M. Rhea4, Natalia Kozyr1,2, Rebecca S. Arnold5, Hinh Ly4, Ross J. Molinaro4,8, Tristram G. Parslow4, Eric Hunter1,2,4, Dennis Liotta7, John Petros4,5,6,9, Jerry L. Blackwell1,2,3*
1 Emory Vaccine Center, Emory University, Atlanta, Georgia, United States of America, 2 Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America, 3 Division of Infectious Diseases, Emory University, Atlanta, Georgia, United States of America, 4 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America, 5 Department of Urology, Emory University, Atlanta, Georgia, United States of America, 6 Department of Hematology-Oncology, Emory University, Atlanta, Georgia, United States of America, 7 Department of Chemistry, Emory University, Atlanta, Georgia, United States of America, 8 Core Laboratories Emory University Hospital Midtown, Emory University, Atlanta, Georgia, United States of America, 9 Atlanta Veterans Affairs Medical Center, Decatur, Georgia, United States of America
Background
Xenotropic murine leukemia virus-related virus (XMRV) was recently discovered to be the first human gammaretrovirus that is associated with chronic fatigue syndrome and prostate cancer (PC). Although a mechanism for XMRV carcinogenesis is yet to be established, this virus belongs to the family of gammaretroviruses well known for their ability to induce cancer in the infected hosts. Since its original identification XMRV has been detected in several independent investigations; however, at this time significant controversy remains regarding reports of XMRV detection/prevalence in other cohorts and cell type/tissue distribution. The potential risk of human infection, coupled with the lack of knowledge about the basic biology of XMRV, warrants further research, including investigation of adaptive immune responses. To study immunogenicity in vivo, we vaccinated mice with 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.
Results
Immunization elicited Env-specific binding and neutralizing antibodies (NAb) against XMRV in mice. The peak titers for ELISA-binding antibodies and NAb were 1:1024 and 1:464, respectively; however, high ELISA-binding and NAb titers were not sustained and persisted for less than three weeks after immunizations.
Conclusions
Vaccine-induced XMRV Env antibody titers were transiently high, but their duration was short. 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. The low level of immunogenicity observed in the present study may be characteristic of a natural XMRV infection in humans. Full ARTICLE
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