Dual-route targeted vaccine protects efficiently against botulinum neurotoxin A complex |
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| Institution: | 1. Department of Public Health Sciences, University of Connecticut School of Medicine, Farmington, Connecticut;2. Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut;3. Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan;4. Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan;5. Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, Michigan;6. Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut;7. Program in Addiction Medicine, Yale School of Medicine, New Haven,Connecticut;8. Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut;9. Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York;1. 1st Neurology Department, Eginition Hospital, Medical School;2. Research Unit of Radiology, 2nd Department of Radiology, National and Kapodistrian University of Athens, Greece |
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| 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. |
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| Keywords: | Botulinum neurotoxins Target vaccine Dual-route vaccine B cells Dendritic cells |
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