Targeted expression of anthrax protective antigen by Lactobacillus gasseri as an anthrax vaccine

Mansour Mohamadzadeh*, Evelyn Durmaz, Mojgan Zadeh, Krishna Chaitanya Pakanati, Matthew Gramarossa, Valeria Cohran, Todd R. Klaenhammer

*Corresponding author for this work

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Aim: 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. Materials & 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1289-1296
Number of pages8
JournalFuture Microbiology
Volume5
Issue number8
DOIs
StatePublished - Aug 2010

Keywords

  • Lactobacillus gasseri
  • anthrax vaccine
  • dendritic cell
  • high copy expression
  • oral vaccine delivery
  • probiotic

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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    Mohamadzadeh, M., Durmaz, E., Zadeh, M., Pakanati, K. C., Gramarossa, M., Cohran, V., & Klaenhammer, T. R. (2010). Targeted expression of anthrax protective antigen by Lactobacillus gasseri as an anthrax vaccine. Future Microbiology, 5(8), 1289-1296. https://doi.org/10.2217/fmb.10.78