Journal article
Mapping of immune responses following wild-type and mutant ABeta42 plasmid or peptide vaccination in different mouse haplotypes and HLA Class II transgenic mice
Vaccine, v 24(21), pp 4630-4639
22 May 2006
PMID: 16157426
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Although the recent clinical trial of the ABeta42 peptide vaccine against Alzheimer's Disease (AD) has been halted due to adverse events, the apparent clinical utility of this approach underscores the need to further improve the safety of the vaccine, as well as to understand the potential immunological basis for complications. In this study, we examine both humoral and cellular immune responses elicited by immunization with peptide or DNA encoding wild-type and the Flemish and Dutch mutations of ABeta42 (i.e. the beta amyloid peptide spanning amino acids 1–42) in mice of different immune haplotypes as well as HLA Class II transgenic mice. The Flemish and Dutch mutations have been associated with cerebrovascular hemorrhages in affected individuals. These data allow determination of potential immunological responses that could mediate pathology observed with mutant forms of amyloid beta, as well as lead to the generation of safer vaccine preparations. Following peptide or plasmid immunization, antibody responses were measured against the different ABeta42 peptides in an ELISA assay, while T cell epitopes were analyzed through interferon gamma ELISPOT and lymphocyte proliferation assays. B cell mapping studies indicated that sera from all of the haplotype mice vaccinated with any of the ABeta42 peptides reacted specifically to the first 10 amino acids of ABeta42 with the ABeta42 mutants eliciting higher immune responses. ELISPOT analysis, which accessed cellular immune responses indicated that mice expressed differences in Class I epitopes dependent on the different immune haplotypes. These results may have implications for the design of future ABeta42 based vaccines against Alzheimer's Disease.
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Details
- Title
- Mapping of immune responses following wild-type and mutant ABeta42 plasmid or peptide vaccination in different mouse haplotypes and HLA Class II transgenic mice
- Creators
- Michele A. Kutzler - University of PennsylvaniaChuanhai Cao - University of South FloridaYun Bai - University of South FloridaHuiQin Dong - University of South FloridaPhilip Y. Choe - University of PennsylvaniaVera Saulino - University of PennsylvaniaLaura McLaughlin - University of South FloridaAlex Whelan - University of South FloridaAndrew Y. Choo - University of PennsylvaniaDavid B. Weiner - University of PennsylvaniaKenneth E. Ugen - University of South Florida
- Publication Details
- Vaccine, v 24(21), pp 4630-4639
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000238518400033
- Scopus ID
- 2-s2.0-33747094107
- Other Identifier
- 991020550342004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Medicine, Research & Experimental