title: Development and evaluation of candidate vaccine and antitoxin against botulinum neurotoxin serotype F.
abstract: To produce a vaccine suitable for human use, a recombinant non His-tagged isoform of the Hc domain of botulinum neurotoxin serotype F (rFHc) was expressed in Escherichia coli and purified by sequential chromatography. The rFHc was evaluated as a subunit vaccine candidate in mouse model of botulism. A dose-response was observed in both antibody titer and protective efficacy with increasing dosage of rFHc and number of vaccinations. These findings suggest that the rFHc is an effective botulism vaccine candidate. Further, we developed a new antitoxin against botulinum neurotoxin serotype F (BoNT/F) by purifying F(ab')(2) fragments from pepsin digested serum IgGs of horses inoculated with rFHc. The protective effect of the F(ab')(2) antitoxin against BoNT/F was determined both in vitro and in vivo. The results showed that the F(ab')(2) antitoxin could prevent botulism in mice challenged with BoNT/F and effectively delayed progression of paralysis from botulism in the therapeutic setting. Thus, our results provide valuable experimental data for this new antitoxin as a potential candidate for treatment of botulism caused by BoNT/F.
authors.affiliation: Beijing Institute of Biotechnology, Beijing, China. yunzhouyu@163.com
authors.forename: Yun-Zhou
authors.initials: YZ
authors.lastname: Yu
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Zhang
authors.forename: Yao
authors.initials: Y
authors.lastname: Ma
authors.forename: Heng-Qi
authors.initials: HQ
authors.lastname: Zhu
authors.forename: Wen-Bing
authors.initials: WB
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Du
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Zhou
authors.forename: Rui-Lin
authors.initials: RL
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Wei-Yuan
authors.initials: WY
authors.lastname: Yu
authors.forename: Pei-Tang
authors.initials: PT
authors.lastname: Huang
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Sun
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D001904:Botulinum Antitoxin / Q000276:immunology* / Q000627:therapeutic use; D001905:Botulinum Toxins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D001906:Botulism / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D003429:Cross Reactions / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006736:Horses; D007106:Immune Sera / Q000276:immunology; D007116:Immunization, Passive; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D054730:Protein Interaction Domains and Motifs / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D000906:Antibodies; D057134:Antibodies, Neutralizing; D001904:Botulinum Antitoxin; D007106:Immune Sera; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D001905:Botulinum Toxins; C096321:botulinum toxin type F