Dendritic cell targeting of Bacillus anthracis protective antigen expressed by Lactobacillus acidophilus protects mice from lethal challenge.
Efficient vaccines potentiate antibody avidity and increase T cell longevity, which confer protection against microbial lethal challenge. A vaccine strategy was established by using Lactobacillus acidophilus to deliver Bacillus anthracis protective antigen (PA) via specific dendritic cell-targeting peptides to dendritic cells (DCs), which reside in the periphery and mucosal surfaces, thus directing and regulating acquired immunity. The efficiency of oral delivery of L. acidophilus expressing a PA-DCpep fusion was evaluated in mice challenged with lethal B. anthracis Sterne. Vaccination with L. acidophilus expressing PA-DCpep induced robust protective immunity against B. anthracis Sterne compared with mice vaccinated with L. acidophilus expressing PA-control peptide or an empty vector. Additionally, serum anti-PA titers, neutralizing PA antibodies, and the levels of IgA-expressing cells were all comparable with the historical recombinant PA plus aluminum hydroxide vaccine administered s.c. Collectively, development of this strategy for oral delivery of DC-targeted antigens provides a safe and protective vaccine via a bacterial adjuvant that may potentiate mucosal immune responses against deadly pathogens.
Mohamadzadeh
M
M
School of Medicine, Northwestern University, Chicago, IL 60611, USA. m.zadeh@northwestern.edu
Duong
T
T
Sandwick
S J
SJ
Hoover
T
T
Klaenhammer
T R
TR
D000284:Administration, Oral; D000818:Animals; D000881:Anthrax / Q000517:prevention & control; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000917:Antibody Formation; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D001408:Bacillus anthracis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D007109:Immunity; D007779:Lactobacillus acidophilus / Q000235:genetics*; D051379:Mice
D022122:Anthrax Vaccines; D000942:Antigens, Bacterial