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

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

Vaccine. 2018 01 02;36(1):155-164

Authors: Sahay B, Colliou N, Zadeh M, Ge Y, Gong M, Owen JL, Valletti M, Jobin C, Mohamadzadeh M

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.

PMID: 29180028 [PubMed - indexed for MEDLINE]

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