| Recombinant vaccine displaying the loop neutralizing determinant from protective antigen completely protects rabbits from experimental inhalation anthrax. | |
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MedLine Citation:
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PMID: 23283638 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We previously showed that a multiple antigenic peptide (MAP) vaccine displaying a.a. 304-319 from the 2β2-2β3 loop of protective antigen, was capable of protecting rabbits from an aerosolized spore challenge with Bacillus anthracis Ames strain. Antibodies to this sequence, referred to as the loop neutralizing determinant (LND), are highly potent at neutralizing lethal toxin, yet are virtually absent in rabbit and human PA antiserum. While the MAP vaccine was protective against anthrax, it contains a single heterologous helper T cell epitope which may be sub-optimal for stimulating an outbred human population. We, therefore, engineered a recombinant vaccine (Rec-LND) containing two tandemly-repeated copies of the LND fused to maltose binding protein, with enhanced immununogenicity resulting from the p38/P4 helper T cell epitope from Schistosoma mansoni. Rec-LND was found to be highly immunogenic in four, MHC-diverse strains of mice. All (7/7) rabbits immunized with Rec-LND developed high-titered antibody, 6 out of 7 developed neutralizing antibody and all rabbits were protected from a 193-LD(50) aerosolized spore challenge with B. anthracis Ames strain. Survivor serum from Rec-LND-immunized rabbits revealed significantly increased neutralization titers and specific activity compared to pre-challenge levels, yet lacked protective antigen or lethal factor antigenemia. Control rabbits immunized with PA, which were also completely protected, appeared sterilely-immune, exhibiting significant declines in neutralization titer and specific activity compared to pre-challenge levels. We conclude that Rec-LND may represent a prototype anthrax vaccine for use alone or potentially combined with PA-containing vaccines. |
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Authors:
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Jon Oscherwitz; Fen Yu; Jana L Jacobs; Kemp B Cease |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-2 |
Journal Detail:
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Title: Clinical and vaccine immunology : CVI Volume: - ISSN: 1556-679X ISO Abbreviation: Clin. Vaccine Immunol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101252125 Medline TA: Clin Vaccine Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48105. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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