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(Investigative Ophthalmology and Visual Science. 2007;48:4643-4653.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-0356
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Protective Immunity against Ocular Herpes Infection and Disease Induced by Highly Immunogenic Self-Adjuvanting Glycoprotein D Lipopeptide Vaccines

Ilham Bettahi,1 Anthony B. Nesburn,1 Susan Yoon,1 Xiuli Zhang,1 Amir Mohebbi,1 Valerie Sue,1 Aaron Vanderberg,1 Steven L. Wechsler,1 and Lbachir BenMohamed1,2

1From the Laboratory of Cellular and Molecular Immunology, The Eye Institute, School of Medicine, and the 2Center for Immunology, University of California Irvine, Irvine, California.

PURPOSE. An important phase in the development of an ocular herpes simplex virus type 1 (HSV-1) subunit vaccine is the identification of an efficient, safe, and adjuvant-free antigen delivery system capable of inducing and sustaining long-term memory T-cell protective immunity. This study was conducted to test the hypothesis that immunization with self-adjuvanting lipopeptide bearing HSV-1 glycoprotein D (gD) T-cell epitopes would elicit long-term HSV-specific T cells and decrease infection, disease, or both in a ocular herpes mouse model.

METHODS. Five immunodominant CD4+ T-cell peptide epitopes (gD1-29, gD49-82, gD146-179, gD228-257, and gD332-358), recently identified from HSV-1 gD, were covalently linked to a palmitic acid moiety (lipopeptides) and delivered subcutaneously in adjuvant-free saline. The primary and memory T cells induced by these molecularly defined lipopeptides and their protective efficacy were assessed, in terms of virus replication in the eye, ocular disease, and survival.

RESULTS. Three gD lipopeptides, that drive dendritic cell maturation in vitro, induced long-term, virus-specific, IFN-{gamma}-producing CD4+ Th1 responses, associated with a reduction in ocular herpes infection and disease. Immunization with a cocktail of these three highly immunogenic Th1 lipopeptides increased survival, lowered the peak of ocular virus titer, and cleared the ocular disease.

CONCLUSIONS. Vaccination with a mixture self-adjuvanting lipopeptides containing novel HSV-1 immunodominant gD T-cell epitopes protected mice from ocular herpes infection and disease. The strength of protective immunity induced by these lipopeptides together with their safety provide a molecularly defined vaccine formulation that could combat ocular herpes infection and disease in humans.




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X. Zhang, F. A. Castelli, X. Zhu, M. Wu, B. Maillere, and L. BenMohamed
Gender-Dependent HLA-DR-Restricted Epitopes Identified from Herpes Simplex Virus Type 1 Glycoprotein D
Clin. Vaccine Immunol., September 1, 2008; 15(9): 1436 - 1449.
[Abstract] [Full Text] [PDF]


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