Epitopes described in "Recombinant vaccine displaying the loop-neutralizing determinant from protective antigen completely protects rabbits from experimental inhalation anthrax."

Article Authors:Jon Oscherwitz; Fen Yu; Jana L Jacobs; Kemp B Cease
Article Title:Recombinant vaccine displaying the loop-neutralizing determinant from protective antigen completely protects rabbits from experimental inhalation anthrax.
Reference Detail
Reference ID:1025575
Abstract:We previously showed that a multiple antigenic peptide (MAP) vaccine displaying amino acids (aa) 304 to 319 from the 22-23 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.
Affiliations:Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA. joscher@umich.edu.
Reference Type:Literature
PubMed ID:23283638
Journal:Clin Vaccine Immunol
Journal Volume:20
Article Pages:341-9
Journal ISSN:1556-6811
Article Chemical List:Anthrax Vaccines;Antibodies, Bacterial;Antibodies, Neutralizing;Antigens, Bacterial;Bacterial Toxins;Epitopes;Recombinant Fusion Proteins;Vaccines, Synthetic;anthrax toxin
Article MeSH List: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)
Curation Last Updated:2015-07-30 20:47:06