title: DNA vaccines targeting heavy chain C-terminal fragments of Clostridium botulinum neurotoxin serotypes A, B, and E induce potent humoral and cellular immunity and provide protection from lethal toxin challenge.
abstract: Botulinum neurotoxins (BoNTs) are deadly, toxic proteins produced by the bacterium Clostridium botulinum that can cause significant diseases in humans. The use of the toxic substances as potential bioweapons has raised concerns by the Centers for Disease Control and Prevention and the United States Military. Currently, there is no licensed vaccine to prevent botulinum intoxication. Here we present an immunogenicity study to evaluate the efficacy of novel monovalent vaccines and a trivalent cocktail DNA vaccine targeting the heavy chain C-terminal fragments of Clostridium botulinum neurotoxin serotypes A, B, and E. These synthetic DNA vaccines induced robust humoral and polyfunctional CD4(+) T-cell responses which fully protected animals against lethal challenge after just 2 immunizations. In addition, naïve animals administered immunized sera mixed with the lethal neurotoxin were 100% protected against intoxication. The data demonstrate the protective efficacy induced by a combinative synthetic DNA vaccine approach. This study has importance for the development of vaccines that provide protective immunity against C. botulinum neurotoxins and other toxins.
authors.affiliation: a Department of Pathology and Laboratory Medicine ; University of Pennsylvania ; Philadelphia , PA USA.
authors.forename: Veronica L
authors.initials: VL
authors.lastname: Scott
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Villarreal
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Hutnick
authors.forename: Jewell N
authors.initials: JN
authors.lastname: Walters
authors.forename: Edwin
authors.initials: E
authors.lastname: Ragwan
authors.forename: Khalil
authors.initials: K
authors.lastname: Bdeir
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.forename: Adam C
authors.initials: AC
authors.lastname: Finnefrock
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D000992:Antitoxins / Q000097:blood*; D001905:Botulinum Toxins / Q000235:genetics / Q000276:immunology*; D019274:Botulinum Toxins, Type A / Q000235:genetics / Q000276:immunology*; D001906:Botulism / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000992:Antitoxins; D019444:Vaccines, DNA; C096323:rimabotulinumtoxinB; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A; C096326:botulinum toxin type E
keywords: DNA vaccines; Keywords: Botulinum toxins; immunity; neurotoxin; vaccines