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L Benmohamed, B Georges, B Kaplan, SM Slanina, A Bouzidi, H Gras-Masse, SL Wechsler, AB Nesburn; Totally Synthetic HSV-1 Lipopeptides Without Adjuvant, Elicit Immune Responses in Mice and Rabbits . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4324.
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Purpose: To produce totally synthetic lipopeptides based on the amino acid sequences of HSV-1 glycoproteins gB and gD that are capable, without adjuvant, of eliciting strong humoral and cell mediated immune responses in mice and rabbits. It is hoped that a mixture of several immunogenic lipopeptides can then be used as the basis of a safe and efficacious clinical vaccine against ocular HSV-1. Methods: HSV-1 gB and gD were analyzed by the T cell epitope prediction algorithm TEPITOPE. 28 gB and 12 gD universal peptides, each 22 to 40 amino acids in length, were predicted and used in binding assays with 13 different human leukocyte antigen class II (HLA-DR) molecules. High binding affinity peptides were selected. Mice and rabbits were immunized and the B and T cell immunogenicity of each peptide were determined. B cell responses were detected by serum ELISA and neutralizing antibody titers. T-cell responses were detected by proliferation assays, cytokines secretion, and CTL assays. Some of the immunogenic peptides were linked to one molecule of palmitic acid at the C terminus to produce lipopeptides. These lipopeptides were used to immunize mice and rabbits without adjuvant. As a positive control the peptides were also injected with a clinically approved adjuvant Montanide's ISA-720. Results: Peptides plus adjuvant elicited viral neutralizing antibodies and T-cells that reacted to the native protein. T helper responses were Th1 based on selective expansion of CD4 (+) cells with high IFN-γ secretion. Importantly, immunization with gB and gD lipopeptides, in water, induced both B and T cell responses. Conclusion: i) The use of the TEPITOPE program to select universal peptides allowed rapid screening of peptides capable of inducing a Th1 response and in vivo activation of both B- and T-cells. ii) Immunization of mice and rabbits with corresponding lipopeptides in water (without adjuvant) allowed selection of lipopeptides capable of inducing both B and T cell responses. iii) This lipopeptide approach may be a feasible and powerful method of developing a useful immunotherapeutic vaccine for ocular HSV-1 in humans
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