Wednesday, May 18, 2011

The relatively rapid diminution in antibody levels may in part explain the differing prevalences reported for XMRV

Correction: Antibody Responses against Xenotropic Murine Leukemia Virus-Related Virus Envelope in a Murine Model
Some potential competing interests in relation to this work were not declared in the article. The authors apologize for this omission and would like to disclose the following information: Drs Blackwell, Makarova, Molinaro, Suppiah and Ly have a U.S. patent (PCT/US2010/050633) and pending international patent application (WO 2011/041350 A2) on compositions and methods for analyzing and treating a disease, disorder, or condition associated with Xenotropic Murine Leukemia Virus-Related Virus infection.

Natalia Makarova,1,2 Chunxia Zhao,1,2 Yuanyuan Zhang,1,2 Sushma Bhosle,4 Suganthi Suppiah,4 Jeanne M. Rhea,4 Natalia Kozyr,1,2 Rebecca S. Arnold,5 Hinh Ly,4 Ross J. Molinaro,4,8 Tristram G. Parslow,4 Eric Hunter,1,2,4 Dennis Liotta,7 John Petros,4,5,6,9 and Jerry L. Blackwell1,2,3*

1Emory Vaccine Center, Emory University, Atlanta, Georgia, United States of America
2Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America
3Division of Infectious Diseases, Emory University, Atlanta, Georgia, United States of America
4Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America
5Department of Urology, Emory University, Atlanta, Georgia, United States of America
6Department of Hematology-Oncology, Emory University, Atlanta, Georgia, United States of America
7Department of Chemistry, Emory University, Atlanta, Georgia, United States of America
8Core Laboratories Emory University Hospital Midtown, Emory University, Atlanta, Georgia, United States of America
9Atlanta Veterans Affairs Medical Center, Decatur, Georgia, United States of America
Shabaana Khader, Editor
University of Pittsburgh, United States of America
* E-mail: jerry.blackwell@emory.edu

Abstract
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 11024 and 1464, 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.

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