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Author Notes:

Correspondence: Jerry L. Blackwell, Email: jerry.blackwell@emory.edu

Authors' Contributions: Conceived and designed the experiments: NM JLB.

Performed the experiments: NM CZ YZ SB SS.

Analyzed the data: NM RA TGP JP JLB.

Wrote the paper: NM CZ YZ RSA TGP JLB.

Discussions about the study and results: SB SS JMR NK RSA HL RJM TGP EH DL JP.

This research project was supported in part by the expert assistance by Dr. Hong Yi at the Robert P. Apkarian Integrated Electron Microscopy Core of the Emory University School of Medicine.

We thank Drs. J. Olsen for the mAb R187-producing cells, Leonard H. Evans for mAb 83A25 and Robert Silverman for the XMRV-producing DU145-C7 cells.

Disclosures: The authors have declared that no competing interests exist.

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Research Funding:

This work was funded by the Emory Department of Chemistry, Immunology and Developmental Cores of the Emory CFAR (P30-AI050409), Yerkes National Primate Research Center base grant (RR-00165) and National Institutes of Health National Institute of Allergy and Infectious Diseases grants (R01-AI069987, R0-1AI076096-01 and R21-AI076080).

Antibody Responses against Xenotropic Murine Leukemia Virus-Related Virus Envelope in a Murine Model

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Journal Title:

PLoS ONE

Volume:

Volume 6, Number 4

Publisher:

, Pages 1-9

Type of Work:

Article | Final Publisher PDF

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 1[ratio]1024 and 1[ratio]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.

Copyright information:

© 2011 Makarova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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