Dual-route targeted vaccine protects efficiently against botulinum neurotoxin A complex. Issue 1 (2nd January 2018)

• Record Type: Journal Article
• Authors: Sahay, Bikash; Colliou, Natacha; Zadeh, Mojgan; Ge, Yong; Gong, Minghao; Owen, Jennifer L.; Valletti, Melissa; Jobin, Christian; Mohamadzadeh, Mansour
• Is Part Of: Vaccine. Volume 36:Issue 1(2018)
• Page Start: 155
• Page End: 164
• Publication Date: 2018-01-02
• Subjects: BoNT clostridium botulinum neurotoxin -- DCpep dendritic cell binding peptide -- Hc heavy chain of BoNT/A -- CL colon -- MLN mesenteric lymph node -- SP spleen -- PLN peripheral lymph node -- GC germinal center -- Tfh T follicular helper cells; Botulinum neurotoxins -- Target vaccine -- Dual-route vaccine -- B cells -- Dendritic cells; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2017.11.008
• Languages: English
• ISSNs: 0264-410X

Abstract

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.