Journal
VACCINE
Volume 36, Issue 1, Pages 155-164Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2017.11.008
Keywords
Botulinum neurotoxins; Target vaccine; Dual-route vaccine; B cells; Dendritic cells
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Funding
- NIH - United States [R01 AI093370]
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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 naive mice induced robust protection against BoNTIA 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. (C) 2017 Elsevier Ltd. All rights reserved.
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