Document Detail


Recombinant vaccine displaying the loop-neutralizing determinant from protective antigen completely protects rabbits from experimental inhalation anthrax.
MedLine Citation:
PMID:  23283638     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously showed that a multiple antigenic peptide (MAP) vaccine displaying amino acids (aa) 304 to 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 protective antigen (PA) antiserum. While the MAP vaccine was protective against anthrax, it contains a single heterologous helper T cell epitope which may be suboptimal 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 immunogenicity resulting from the p38/P4 helper T cell epitope from Schistosoma mansoni. Rec-LND was found to be highly immunogenic in four major histocompatibility complex (MHC)-diverse strains of mice. All (7/7) rabbits immunized with Rec-LND developed high-titer antibody, 6 out of 7 developed neutralizing antibody, and all rabbits were protected from an aerosolized spore challenge of 193 50% lethal doses (LD(50)) of the B. anthracis Ames strain. Survivor serum from Rec-LND-immunized rabbits revealed significantly increased neutralization titers and specific activity compared to prechallenge levels yet lacked PA or lethal factor (LF) 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 prechallenge levels. We conclude that Rec-LND may represent a prototype anthrax vaccine for use alone or potentially combined with PA-containing vaccines.
Authors:
Jon Oscherwitz; Fen Yu; Jana L Jacobs; Kemp B Cease
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-02
Journal Detail:
Title:  Clinical and vaccine immunology : CVI     Volume:  20     ISSN:  1556-679X     ISO Abbreviation:  Clin. Vaccine Immunol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-08-19     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  101252125     Medline TA:  Clin Vaccine Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  341-9     Citation Subset:  IM    
Affiliation:
Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA. joscher@umich.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Anthrax / immunology,  prevention & control*
Anthrax Vaccines / administration & dosage,  genetics,  immunology*
Antibodies, Bacterial / blood
Antibodies, Neutralizing / blood
Antigens, Bacterial / genetics,  immunology*
Bacterial Toxins / genetics,  immunology*
Disease Models, Animal
Epitopes / genetics,  immunology
Female
Humans
Mice
Rabbits
Recombinant Fusion Proteins / genetics,  immunology
Respiratory Tract Infections / immunology,  prevention & control*
Survival Analysis
Vaccines, Synthetic / administration & dosage,  genetics,  immunology
Grant Support
ID/Acronym/Agency:
U01-AI56580/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anthrax Vaccines; 0/Antibodies, Bacterial; 0/Antibodies, Neutralizing; 0/Antigens, Bacterial; 0/Bacterial Toxins; 0/Epitopes; 0/Recombinant Fusion Proteins; 0/Vaccines, Synthetic; 0/anthrax toxin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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