Development and evaluation of candidate vaccine and antitoxin against botulinum neurotoxin serotype F.
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.
Yu
Yun-Zhou
YZ
Beijing Institute of Biotechnology, Beijing, China. yunzhouyu@163.com
Zhang
Shu-Ming
SM
Ma
Yao
Y
Zhu
Heng-Qi
HQ
Wang
Wen-Bing
WB
Du
Yun
Y
Zhou
Xiao-Wei
XW
Wang
Rui-Lin
RL
Wang
Shuang
S
Yu
Wei-Yuan
WY
Huang
Pei-Tang
PT
Sun
Zhi-Wei
ZW
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*
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