Dendritic cell targeting ofBacillus anthracisprotective antigen expressed byLactobacillus acidophilusprotects mice from lethal challenge

Mansour Mohamadzadeh1, Tri Duong2,3, S. J. Sandwick4, Timothy A. Hoover4, Todd R. Klaenhammer2,3
1School of Medicine, Northwestern University, Chicago, IL 60611;
2Department of Food Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, NC 27695
3Genomic Sciences Graduate Program and
4United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21792; and

Tóm tắt

Efficient vaccines potentiate antibody avidity and increase T cell longevity, which confer protection against microbial lethal challenge. A vaccine strategy was established by usingLactobacillus acidophilusto deliverBacillus anthracisprotective 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 ofL. acidophilusexpressing a PA-DCpep fusion was evaluated in mice challenged with lethalB. anthracisSterne. Vaccination withL. acidophilusexpressing PA-DCpep induced robust protective immunity againstB. anthracisSterne compared with mice vaccinated withL. acidophilusexpressing 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.

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