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Hum Immunol. 2012 Jun;73(6):612-9. doi: 10.1016/j.humimm.2012.03.009. Epub 2012 Apr 12.

Evaluation of a non-viral vaccine in smallpox-vaccinated individuals and immunized HLA-transgenic mice.

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  • 1Center for Molecular Medicine and Immunology/Garden State Cancer Center (CMMI/GSCC), 300 The American Road, Morris Plains, NJ 07950, USA. ataylor@gscancer.org

Abstract

The current poxvirus vaccine is associated with rare, but serious adverse events. Therefore, we investigated a non-replicating approach to vaccine design. Peptides encoding potential HLA-binding motifs were derived from the orthopoxvirus genes, D8L, A27L, and C12L (the IL-18-binding protein [vIL18BP105]), all of which are preserved among poxviruses that infect humans, and which may be a target of host immunity. The peptides were tested with poxvirus-vaccinated human PBMC and serum for eliciting memory responses, as well as with splenocytes and serum from peptide-immunized, human HLA-DR04 transgenic (HLA tg) mice. vIL18BP105 induced 5-fold proliferation of vaccinated-donor PBMC over non-vaccinated (P<0.001), including IL-2-producing CD8+ cells. Serum IgG recognizing vIL18BP105 was detected (P<0.002 vs non-vaccinated) by ELISA. Viral peptides were conjugated to the HLA-targeting mAb, L243, for immunization of HLA tg mice. Splenocytes from vIL18BP105-L243-immunized mice proliferated upon exposure to vIL18BP105 (P<0.001). Proliferating splenocytes were interferon-γ-producing CD4(+)CD45RA(neg). vIL18BP105-L243-immunized mice generated IgG more rapidly than free-peptide-immunized mice. Peptide-specific antibody was also detected when different L243-peptide conjugates were combined. vIL18BP, by eliciting human memory responses, is a viable antigen for inclusion in a virus-free vaccine. The immunogenicity of peptides was boosted by conjugation to L243, whether administered alone or combined.

Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

PMID:
22504409
[PubMed - indexed for MEDLINE]
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