Publications by authors named "Yun-Zhou Yu"

Three 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 PDF

Tetanus 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 PDF

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 PDF

Objectives: 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.

View Article and Find Full Text PDF
Article Synopsis
  • Botulinum neurotoxins (BoNTs) cause botulism in humans, which can be treated effectively with antitoxins; researchers developed a new antitoxin using recombinant C terminal heavy chain domains from BoNTs.* -
  • The initial antitoxins created (M-BATs) targeted individual BoNT serotypes (A, B, E, F) but lacked cross-protection, leading to the need for a more comprehensive tetravalent antitoxin (T-BAT) capable of neutralizing all four at once.* -
  • The T-BAT demonstrated strong effectiveness in animal models, binding efficiently to the receptor-binding domain (RBD) of the toxins, suggesting this strategy
View Article and Find Full Text PDF

Botulinum 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 PDF

Botulinum neurotoxin (BoNT) is a neurotoxin produced by Clostridium botulinum in an anaerobic environment. BoNT is the most toxic protein among bacteria, animals, plants, and chemical substances reported to date. BoNTs are 150 kDa proteins composed of three major functional domains: catalytic (L domain, 50 kDa), translocation (HN domain, 50 kDa), and receptor-binding (Hc domain, 50 kDa) domains.

View Article and Find Full Text PDF
Article Synopsis
  • * Tests on mice showed that the THc-based vaccine provided complete protection against tetanus, outperforming the current full-length TT vaccine in generating stronger immune responses.
  • * The THc protein also interacts with a specific ganglioside (GT1b), and the antibodies generated from the THc vaccine can block this interaction, indicating that the recombinant THc could serve as an effective subunit vaccine against tetanus.
View Article and Find Full Text PDF

Botulinum neurotoxins (BoNTs) are highly toxic proteins that mediate their effects by binding to neuronal receptors and block the neutralizing ability of therapeutic antibodies. Vaccination is currently the most effective strategy to prevent botulism. In this study, a series of recombinant functional domain antigens of BoNT/A were prepared and identified, and their immunoprotective efficacies were explored and compared.

View Article and Find Full Text PDF

Botulinum neurotoxins (BoNTs) are among the most toxic proteins. Vaccination is an effective strategy to prevent botulism. To generate a vaccine suitable for human use, a recombinant non-His-tagged isoform of the Hc domain of botulinum neurotoxin serotype E (rEHc) was expressed in and purified by sequential chromatography.

View Article and Find Full Text PDF

Botulinum neurotoxins (BoNTs) are potential biological weapons because of their high toxicity and mortality. Vaccination is an effective strategy to prevent botulism. The carboxyl-terminus of the heavy chain (Hc domain) is nontoxic and sufficient to generate protective immune responses against natural BoNTs in animals.

View Article and Find Full Text PDF

Strategies for targeting CD47 are becoming a hot spot of cancer immunotherapy. However the ubiquitous expression of CD47, especially on the RBC, makes the targeted therapy facing safety risk issues. So, how to balance the safety and efficacy during CD47 inhibition is currently a major question.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder impairing memory and cognition. In this study, we describe the immunogenicity and protective efficacy of the novel recombinant 6Aβ15-TF chimeric antigen as a subunit protein vaccine for AD. Recombinant 6Aβ15-TF chimeric vaccine induced strong Aβ-specific humoral immune responses without Aβ-specific T cell immunity in C57/BL6 and 3 × Tg-AD mice at different ages.

View Article and Find Full Text PDF

Human respiratory syncytial virus (RSV) is the most significant cause of acute lower respiratory infection in children. However, there is no licensed vaccine available. Here, we investigated the effect of five or 20 copies of C-Class of CpG ODN (CpG-C) motif incorporated into a plasmid DNA vaccine encoding RSV fusion (F) glycoprotein on the vaccine-induced immune response.

View Article and Find Full Text PDF

As dendritic cells (DCs) play a critical role in priming antigen-specific immune responses, the efficacy of DNA vaccines may be enhanced by targeting the encoded antigen proteins to DCs. In this study, we constructed a DC-targeted DNA vaccine encoding the Hc domain of botulinum neurotoxin serotype A (AHc) fused with scDEC, a single-chain Fv antibody (scFv) specific for the DC-restricted antigen-uptake receptor DEC205. Intramuscular injections of mice with the DC-targeted DNA vaccine (pVAX1-scDEC-AHc) stimulated more DCs to mature than the non-targeted DNA vaccine (pVAX1-SAHc) in the splenocytes.

View Article and Find Full Text PDF

Targeting antigens encoded by DNA vaccines to the key antigen-presenting cells by chemotactic or growth factors, is an effective strategy for enhancing the potency of DNA vaccinations. Here, we report the effects of chemotactic or growth factors on a DNA vaccine against botulinum neurotoxin serotype A (BoNT/A) in a mouse model. We demonstrated that mice immunized with DNA constructs encoding the Hc domain of BoNT/A (AHc) fused with DC-stimulating Flt3L or MIP-3α cytokines failed to elicit an enhanced or efficacious AHc-specific humoral or protective response in mice.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. The neuropathological features of the disease include senile plaques (SPs), neurofibrillary tangles (NFTs) and neuronal loss in affected brain regions. The amyloid cascade hypothesis suggests that production and accumulation of excessive amyloid-β (Aβ) may be the main cause in the onset and progression of Alzheimer's disease.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-β (Aβ) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6Aβ15-THc-C immunogen was formulated with alum adjuvant as a novel Aβ B-cell epitope candidate vaccine (rCV02) for AD.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive amyloid-β accumulation, loss of cognitive abilities, and synaptic alterations. Given the remarkable recovery of cognition in AD models of targeting-Aβ immunotherapy, we sought to determine the molecular correlate(s) associated with improvement. We evaluated the efficacy of a recombinant chimeric 6Aβ15-T antigen formulated with alum adjuvant as a novel Aβ B-cell epitope vaccine (rCV01) in 3 × Tg-AD mice.

View Article and Find Full Text PDF

Active and passive immunotherapy targeting amyloid-β (Aβ) may be the most promising strategy to prevent or treat Alzheimer's disease (AD). Previously, immunization with the recombinant 6Aβ15-T antigen generated robust anti-Aβ serum antibodies that strongly recognized Aβ42 oligomers in different mice, markedly reduced the amyloid burden, and improved behavioral performance of immunized older AD mice. Here, we further determined that these anti-6Aβ15-T serum antibodies from different strains of mice displayed anti-Aβ antibody responses against the same epitopes in the Aβ1-15 region.

View Article and Find Full Text PDF

Active immunotherapy targeting β-amyloid (Aβ) is the most promising strategy to prevent or treat Alzheimer's disease (AD). Based on pre-clinical studies and clinical trials, a safe and effective AD vaccine requires a delicate balance between providing therapeutically adequate anti-Aβ antibodies and eliminating or suppressing unwanted adverse T cell-mediated inflammatory reactions. We describe here the immunological characterization and protective efficacy of co-immunization with a 6Aβ15-T DNA and protein mixture without adjuvant as an AD immunotherapeutic strategy.

View Article and Find Full Text PDF

The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities.

View Article and Find Full Text PDF

Although Escherichia coli and yeast were commonly used to express recombinant Hc of botulinum neurotoxins, as an alternative, in current study, a 293E expression system was used to express the Hc of botulinum neurotoxin serotype B (BHc) as soluble recombinant protein for experimental vaccine evaluation. Our results demonstrated that the 293E expression system could produce high level of recombinant secreted BHc protein, which was immunorecognized specifically by anti-botulinum neurotoxin serotype B (BoNT/B) sera and showed ganglioside binding activities. The serological response and efficacy of recombinant BHc formulated with aluminum hydroxide adjuvant were evaluated in mice.

View Article and Find Full Text PDF

The clostridial neurotoxin (CNT) family includes botulinum neurotoxin (BoNT), serotypes A, B, E, and F of which can cause human botulism, and tetanus neurotoxin (TeNT), which is the causative agent of tetanus. This suggests that the greatest need is for a multivalent or multiagent vaccine that provides protection against all 5 agents. In this study, we investigated the feasibility of generating several pentavalent replicon vaccines that protected mice against BoNTs and TeNT.

View Article and Find Full Text PDF

DNA vaccines are generally weak stimulators of the immune system. Fortunately, their efficacy can be improved using a viral replicon vector or by the addition of immunostimulatory CpG motifs, although the design of these engineered DNA vectors requires optimization. Our results clearly suggest that multiple copies of three types of CpG motifs or combinations of various types of CpG motifs cloned into a viral replicon vector backbone with strong immunostimulatory activities on human PBMC are efficient adjuvants for these DNA vaccines to modulate and enhance protective immunity against anthrax, although modifications with these different CpG forms in vivo elicited inconsistent immune response profiles.

View Article and Find Full Text PDF