title: Induction of protective neutralizing antibody responses against botulinum neurotoxin serotype C using plasmid carried by PLGA nanoparticles.
abstract: Botulinum neurotoxin (BoNT) is a lethal neurotoxin, for which there is currently not an approved vaccine. Recent efforts in developing vaccine candidates against botulism have been directed at the heavy chain fragment of BoNT, because antibodies against this region have been shown to prevent BoNT from binding to its receptor and thus to nerve cell surface, offering protection against BoNT intoxication. In the present study, it was shown that immunization with plasmid DNA that encodes the 50 KDa C-terminal fragment of the heavy chain of BoNT serotype C (i.e., BoNT/C-Hc50) and is carried by cationic poly (lactic-co-glycolic) acid (PLGA) nanoparticles induces stronger BoNT/C-specific antibody responses, as compared to immunization with the plasmid alone. Importantly, the antibodies have BoNT/C-neutralizing activity, protecting the immunized mice from a lethal dose of BoNT/C challenge. A plasmid DNA vaccine encoding the Hc50 fragments of BoNT serotypes that cause human botulism may represent a viable vaccine candidate for protecting against botulinum neurotoxin intoxication.
authors.affiliation: a College of Pharmacy, Pharmaceutics Division, The University of Texas at Austin , Austin , TX , USA.
authors.forename: Tinashe B
authors.initials: TB
authors.lastname: Ruwona
authors.affiliation: a College of Pharmacy, Pharmaceutics Division, The University of Texas at Austin , Austin , TX , USA.
authors.forename: Haiyue
authors.initials: H
authors.lastname: Xu
authors.affiliation: b Department of Biomedical Sciences , Center of Emphasis in Infectious Diseases, Texas Tech University Health Sciences Center El Paso , El Paso , TX , USA.
authors.forename: Junwei
authors.initials: J
authors.lastname: Li
authors.affiliation: b Department of Biomedical Sciences , Center of Emphasis in Infectious Diseases, Texas Tech University Health Sciences Center El Paso , El Paso , TX , USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Diaz-Arévalo
authors.affiliation: a College of Pharmacy, Pharmaceutics Division, The University of Texas at Austin , Austin , TX , USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: b Department of Biomedical Sciences , Center of Emphasis in Infectious Diseases, Texas Tech University Health Sciences Center El Paso , El Paso , TX , USA.
authors.forename: Mingtao
authors.initials: M
authors.lastname: Zeng
authors.affiliation: a College of Pharmacy, Pharmaceutics Division, The University of Texas at Austin , Austin , TX , USA.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology; D001905:Botulinum Toxins / Q000235:genetics / Q000276:immunology*; D001906:Botulism / Q000517:prevention & control; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D019344:Lactic Acid; D051379:Mice; D053758:Nanoparticles; D010957:Plasmids; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D065288:Serogroup; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D001905:Botulinum Toxins; C096324:botulinum toxin type C
keywords: PLGA nanoparticles; antibody responses; botulinum neurotoxin; mouse survival
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