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Journal of Virology, September 2003, p. 9463-9473, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9463-9473.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Identification of Novel Immunodominant CD4+ Th1-Type T-Cell Peptide Epitopes from Herpes Simplex Virus Glycoprotein D That Confer Protective Immunity

Lbachir BenMohamed,1* Georges Bertrand,2 Cory D. McNamara,3 Helene Gras-Masse,2,4 Juergen Hammer,5 Steven L. Wechsler,1 and Anthony B. Nesburn1

Department of Ophthalmology, University of California—Irvine, College of Medicine, Orange, California 92868,1 Burns & Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048,3 SEDAC Therapeutics,2 Chimie des Biomolécules, UMR 8525, Pasteur Institute, Lille, France,4 Section of Bioinformatics, Genetics and Genomics, Hoffmann-La Roche, Nutley, New Jersey 071105

Received 3 March 2003/ Accepted 27 May 2003

The molecular characterization of the epitope repertoire on herpes simplex virus (HSV) antigens would greatly expand our knowledge of HSV immunity and improve immune interventions against herpesvirus infections. HSV glycoprotein D (gD) is an immunodominant viral coat protein and is considered an excellent vaccine candidate antigen. By using the TEPITOPE prediction algorithm, we have identified and characterized a total of 12 regions within the HSV type 1 (HSV-1) gD bearing potential CD4+ T-cell epitopes, each 27 to 34 amino acids in length. Immunogenicity studies of the corresponding medium-sized peptides confirmed all previously known gD epitopes and additionally revealed four new immunodominant regions (gD49-82, gD146-179, gD228-257, and gD332-358), each containing naturally processed epitopes. These epitopes elicited potent T-cell responses in mice of diverse major histocompatibility complex backgrounds. Each of the four new immunodominant peptide epitopes generated strong CD4+ Th1 T cells that were biologically active against HSV-1-infected bone marrow-derived dendritic cells. Importantly, immunization of H-2d mice with the four newly identified CD4+ Th1 peptide epitopes but not with four CD4+ Th2 peptide epitopes induced a robust protective immunity against lethal ocular HSV-1 challenge. These peptide epitopes may prove to be important components of an effective immunoprophylactic strategy against herpes.

* Corresponding author. Mailing address: The Department of Ophthalmology, University of California—Irvine, College of Medicine, Orange, CA 92868. Phone: (714) 456-7371. Fax: (714) 456-5073. E-mail: Lbenmoha{at}uci.edu.

Journal of Virology, September 2003, p. 9463-9473, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9463-9473.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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