Targeted expression of anthrax protective antigen by Lactobacillus gasseri as an anthrax vaccine.
OBJECTIVE
Induction of protective immunity against pathogenic microbes, including Bacillus anthracis, requires efficient vaccines that potentiate antibody avidity and increase T-cell longevity. We recently reported that the delivery of targeted B. anthracis protective antigen (PA) genetically fused to a DC-binding peptide (DCpep) by Lactobacillus acidophilus induced mucosal and systemic immunity against B. anthracis challenge in mice.


METHODS
Improvement of this oral vaccine strategy was attempted by use of the high copy and genetically stable q-replicating vector, pTRKH2, for expression of the targeted PA fusion protein in Lactobacillus gasseri, a common human commensal microbe, to vaccinate animals against anthrax Sterne infection.


RESULTS
Oral application of L. gasseri expressing the PA-DCpep fusion proteins elicited robust PA-neutralizing antibody and T-cell mediated immune responses against anthrax Sterne challenge, resulting in complete animal survival. Collectively, this improved expression vaccine strategy reduced the number of inoculations and length of the boosting period, leading to animal protection via efficacious bacterial adjuvanticity and safe oral delivery of this vaccine to mucosal immune cells, including dendritic cells.


CONCLUSIONS
Lactobacillus-based delivery offers tremendous practical advantages. Recombinant antigens such as PA would not require chemical coupling agents, and the recombinant bacteria can be administered orally where upon both mucosal and systemic immune responses are elicited.
Mohamadzadeh
Mansour
M
Northwestern University, Feinberg School of Medicine, 303 E. Chicago Ave, Chicago, IL 60611, USA. m.zadeh@northwestern.edu
Durmaz
Evelyn
E
Zadeh
Mojgan
M
Pakanati
Krishna Chaitanya
KC
Gramarossa
Matthew
M
Cohran
Valeria
V
Klaenhammer
Todd R
TR
D000284:Administration, Oral; D000818:Animals; D000881:Anthrax / Q000517:prevention & control; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D000992:Antitoxins / Q000097:blood; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D007778:Lactobacillus / Q000235:genetics* / Q000276:immunology; D051379:Mice; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D011993:Recombinant Fusion Proteins; C030325:anthrax toxin