Dual-route targeted vaccine protects efficiently against botulinum neurotoxin A complex

Bikash Sahay, Natacha Colliou, Mojgan Zadeh, Yong Ge, Minghao Gong, Jennifer L. Owen, Melissa Valletti, Christian Jobin, Mansour Mohamadzadeh

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Clostridium botulinum readily persists in the soil and secretes life-threatening botulinum neurotoxins (BoNTs) that are categorized into serotypes A to H, of which, serotype A (BoNT/A) is the most commonly occurring in nature. An efficacious vaccine with high longevity against BoNT intoxication is urgent. Herein, we developed a dual-route vaccine administered over four consecutive weeks by mucosal and parenteral routes, consisting of the heavy chain (Hc) of BoNT/A targeting dendritic cell peptide (DCpep) expressed by Lactobacillus acidophilus as a secretory immunogenic protein. The administered dual-route vaccine elicited robust and long-lasting memory B cell responses comprising germinal center (GC) B cells and follicular T cells (Tfh) that fully protected mice from lethal oral BoNT/A fatal intoxication. Additionally, passively transferring neutralizing antibodies against BoNT/A into naïve mice induced robust protection against BoNT/A lethal intoxication. Together, a targeted vaccine employing local and systemic administrative routes may represent a novel formulation eliciting protective B cell responses with remarkable longevity against threatening biologic agents such as BoNTs.

Original languageEnglish (US)
Pages (from-to)155-164
Number of pages10
JournalVaccine
Volume36
Issue number1
DOIs
StatePublished - Jan 2 2018
Externally publishedYes

Keywords

  • B cells
  • Botulinum neurotoxins
  • Dendritic cells
  • Dual-route vaccine
  • Target vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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