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Journal of Virology, November 2009, p. 11734-11745, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.00578-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Induction of Therapeutic Antibodies by Vaccination against External Loops of Tumor-Associated Viral Latent Membrane Protein{triangledown}

Catherine Delbende,1,2 Claudie Verwaerde,2 Alexandra Mougel,2 and Denis Tranchand Bunel2,3*

Neuroimmunity Laboratory, SN3, Lille1 University, 59655 Villeneuve d'Ascq, France,1 CNRS UMR8527, Laboratory of Immunopathology of Infectious Diseases, IBL5, Pasteur Institute of Lille, 1 rue Pr Calmette, 59021 Lille, France,2 University of Rouen, Faculty of Sciences, Place E. Blondel, 76021 Mont-Saint-Aignan Cédex, France3

Received 20 March 2009/ Accepted 17 August 2009

Some human herpesviruses (HHV) are etiological contributors to a wide range of malignant diseases. These HHV express latent membrane proteins (LMPs), which are type III membrane proteins consistently exposed at the cell surface in these malignancies. These LMPs have relatively large cytoplasmic domains but only short extracellular loops connecting transmembrane segments that are accessible at the surface of infected cells, but they do not elicit antibodies in the course of natural infection and tumorigenesis. We report here that conformational peptides mimicking two adjacent loops of the Epstein-Barr virus (EBV) LMP1 (2LS peptides) induce high-affinity antibodies with remarkable antitumor activities in mice. In active immunization experiments, LMP1-targeting 2LS vaccine conferred tumor protection in BALB/c mice. Moreover, this tumor protection is dependent upon a humoral anti-2LS immune response as demonstrated in DO11.10 (TCR-OVA) mice challenged with LMP1-expressing tumor and in SCID mice xenografted with human EBV-positive lymphoma cells. These data provide a proof of concept for 2LS immunization against short external loops of viral LMPs. This approach might possibly be extended to other infectious agents expressing type III membrane proteins.

* Corresponding author. Mailing address: Institut Pasteur de Lille, IBL5, CNRS UMR8527, 1 rue Pr Calmette, 59021 Lille, France. Phone: 33 320520211. Fax: 33 320871233. E-mail: denis.tranchandbunel{at}univ-rouen.fr

{triangledown} Published ahead of print on 2 September 2009.

Journal of Virology, November 2009, p. 11734-11745, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.00578-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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