Botulinum neurotoxins (BoNTs), including serotypes A and E, are potent biotoxins known to cause human poisoning. In addition to the critical protective antigen found in the full BoNT molecule, the receptor binding domain (Hc domain), BoNTs also harbour another essential protective antigen-the light chain-translocation domain (L-HN domain). Leveraging these pivotal protective antigens, we genetically engineered a series of inactivated chimeric molecules incorporating L-HN and Hc domains of BoNT/A and E.
View Article and Find Full Text PDFBotulinum neurotoxin (BoNT), produced by , is the most toxic protein known, capable of causing severe paralysis and posing a significant bioterrorism threat due to its extreme lethality even in minute quantities. Despite this, there are currently no FDA-approved vaccines for widespread public use. To address this urgent need, we have developed an innovative vaccine platform by fusing the neuronal binding domain of BoNT/E (Hc/E) with core-streptavidin (CS), resulting in a stable CS-Hc/E vaccine.
View Article and Find Full Text PDFBotulinum toxin (BoNT) from Clostridium botulinum is the most toxic biotoxin known and is also an important bioterrorism agent. After poisoning, the only effective treatment is injection of antitoxin. However, neutralizing nanoantibodies are safer and more effective, representing a promising therapeutic approach.
View Article and Find Full Text PDFHum Vaccin Immunother
December 2024
Among all natural and synthetic toxins, botulinum neurotoxins (BoNTs), produced by in an anaerobic environment, are the most toxic polymer proteins. Currently, the most effective modalities for botulism prevention and treatment are vaccination and antitoxin use, respectively. However, these modalities are associated with long response time for active immunization, side effects, and donor limitations.
View Article and Find Full Text PDFThree pandemics caused by human Betacoronavirus had broken out in the past two decades. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was one of the novel epidemic strains which caused the third pandemic, coronavirus disease 2019 (COVID-19), a global public health crisis. So far, more than millions of people have been infected.
View Article and Find Full Text PDFBotulinum neurotoxin (BoNT) shows high lethality and toxicity, marking it as an important biological threat. The only effective post-exposure therapy is botulinum antitoxin; however, such products have great potential for improvement. To prevent or treat BoNT, monoclonal antibodies (mAbs) are promising agents.
View Article and Find Full Text PDFTetanus toxin (TeNT) is a protein toxin produced by Clostridium tetani bacteria, which causes hyperreflexia and rhabdomyolysis by spastic paralysis. Like botulinum neurotoxin, TeNT comprises a heavy chain (HC) and a light chain (LC) linked via an interchain disulfide bond, which include the following three functional domains: a receptor-binding domain (Hc), a translocation domain (HN), and a catalytic domain (LC). Herein, we produced and characterized three functional domains of TeNT and three types of TeNT-derived L-HN fragments (TL-HN, TL-GS-HN and TL-2A-HN), which contained L and HN domains but lacked the Hc domain.
View Article and Find Full Text PDFAppl Microbiol Biotechnol
December 2023
Tetanus toxin (TeNT) and botulinum neurotoxins (BoNTs) are neuroprotein toxins, with the latter being the most toxic known protein. They are structurally similar and contain three functional domains: an N-terminal catalytic domain (light chain), an internal heavy-chain translocation domain (HN domain), and a C-terminal heavy chain receptor binding domain (Hc domain or RBD). In this study, fusion functional domain molecules consisting of the TeNT RBD (THc) and the BoNT/A RBD (AHc) (i.
View Article and Find Full Text PDFObjectives: The mature botulinum neurotoxin (BoNT) is a long peptide chain consisting of a light chain (L) and a heavy chain (H) linked by a disulfide bond, where the heavy chain is divided into a translocation domain and an acceptor binding domain (Hc). In this study, we further explored the biology activity and characteristics of recombinant L-HN fragment (EL-HN) composed of the L and HN domains of BoNT/E in vivo and in vitro.
Methods: Neurotoxicity of L-HN fragments from botulinum neurotoxins was assessed in mice.
Human adenovirus type 7 (HAdV7) is commonly associated with febrile acute respiratory disease (ARD) outbreaks. We have reported that 10G12, a mouse monoclonal antibody (mAb) specifically recognizing and neutralizing HAdV7, is a promising candidate for humanization. In this study, we engineered the six variants of 10G12 with increased degree of humanization and investigated their biological activity.
View Article and Find Full Text PDFBackground: Human adenovirus type 55 (HAdV55) has a re-emerged as pathogen causing an acute respiratory disease presenting as a severe lower respiratory illness that can cause death. To date, there is no HAdV55 vaccine or treatment available for general use.
Methods: Herein, a monoclonal antibody specific for HAdV55, mAb 9-8, was isolated from an scFv-phage display library derived from mice immunized with the purified inactived-HAdV55 virions.
Botulinum neurotoxins (BoNTs) can cause nerve paralysis syndrome in mammals and other vertebrates. BoNTs are the most toxic biotoxins known and are classified as Class A biological warfare agents. BoNTs are mainly divided into seven serotypes A-G and new neurotoxins BoNT/H and BoNT/X, which have similar functions.
View Article and Find Full Text PDFBackground: As a Class A bioterrorism agent, botulinum neurotoxin serotype A (BoNT/A) carries the risk of being used by terrorists to cause mass poisoning. The microneedle (MN) patch has a great potential for application as a novel vaccine delivery method. The aim of this study is to develop a thermally stable, dissolving microneedle patch for the delivery of a recombinant protein vaccine using a recombinant C-terminal heavy chain of BoNT/A (Hc of BoNT/A, AHc) to prevent botulism.
View Article and Find Full Text PDFα-conotoxin AuIB is the only one of the 4/6 type α-conotoxins (α-CTxs) that inhibits the γ-aminobutyric acid receptor B (GABAR)-coupled N-type calcium channel (Ca2.2). To improve its inhibitory activity, a series of variants were synthesized and evaluated according to the structure-activity relationships of 4/7 type α-CTxs targeting GABAR-coupled Ca2.
View Article and Find Full Text PDFBotulinum toxin A(BoNT/A) is a neurotoxin produced by the bacteria , which can cause serious food poisoning and is recognized as a potential biological warfare agent. BoNT/A is does not degrade easily and can remain in the complex matrix for a long time. Meanwhile, the poisonous dose of botulinum toxin exceptionally low and intravenous human lethal doses estimated at 1-3 ng/kg.
View Article and Find Full Text PDFDengue virus (DENV) is a prevalent mosquito-transmitted human pathogen, causing about 100 million cases of acute dengue fever and 21,000 deaths annually worldwide. Therapeutic neutralizing antibodies against dengue virus might be effective to treat severe dengue fever. Here, we showed that human monoclonal antibody (HMAb) 9C7 bound to all four intact serotypes of DENV but not to the recombinant envelope protein, suggesting HMAb 9C7 recognized a conformational epitope of the envelope protein.
View Article and Find Full Text PDFA series of novel conjugates of benzoselenazole or selenazole and CPI-1 were designed, synthesized, and evaluated for inhibitory activities against the botulinum neurotoxin A (BoNT/A) light chain (LC) and BoNT/A in vivo. The results show that these compounds exhibit potent inhibitory activities to the LC with IC of 0.5-4.
View Article and Find Full Text PDFThe emerging coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the causative agent of coronavirus disease 2019 (COVID-19), which has become a severe threat to global public health and local economies. In this study, several single-chain antibody fragments that bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein were identified and used to construct human-mouse chimeric antibodies and humanized antibodies. These antibodies exhibited strong binding to RBD and neutralization activity towards a SARS-CoV-2 pseudovirus.
View Article and Find Full Text PDFBotulinum neurotoxins (BoNTs) are the most toxic known proteins. Naturally occurring botulism in humans is caused by botulinum serotypes A, B, E, and F. Vaccination is an effective strategy to prevent botulism.
View Article and Find Full Text PDFproduces botulinum neurotoxin (BoNT), which is the most toxic known protein and the causative agent of human botulism. BoNTs have similar structures and functions, comprising three functional domains: catalytic domain (L), translocation domain (HN), and receptor-binding domain (Hc). In the present study, BoNT/E was selected as a model toxin to further explore the immunological significance of each domain.
View Article and Find Full Text PDFBotulinum neurotoxin (BoNT), produced by Clostridium botulinum, is generally known to be the most poisonous of all biological toxins. In this study, we evaluate the protection conferred by intratracheal (i.t.
View Article and Find Full Text PDFIn tropical and subtropical countries, dengue virus (DENV) infections have been increasing; however, we still lack effective therapy. In the present study, we aimed to engineer a bispecific antibody (subsequently named LUZ-8F2-6B1), based on monoclonal antibody 6B1, which has anti DENV-1, 2, and 3 activity, and 8F2, which has anti DENV-4 activity. LUZ-8F2-6B1 displayed potent neutralization activity against four serotypes of DENV by binding to the envelop protein.
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