Development and evaluation of candidate subunit vaccine against botulinum neurotoxin serotype B

Shi, Danyang; Chen, Boyang; Mao, Yunyun; Zhou, Guo; Lu, Jian-Sheng; Yu, Yun-Zhou; Zhou, Xiaowei; Sun, Zhiwei

doi:10.1080/21645515.2018.1547613

Cited by 13 publications

(9 citation statements)

References 29 publications

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“…In the last 20 years, the immunological significance of the Hc domain of BoNTs has been the subject of intensive research, leading to important findings [14][15][16][20][21][22][23][24][25]. Our research also indicated that the Hc domain is an effective protective antigen in subunit vaccines for BoNT/A, B, E, and F [26][27][28][29]. However, the immunogenicity of other regions requires further study, such as their protective efficacy and the synergistic effects of multiple epitopes.…”

Section: Discussionmentioning

confidence: 82%

Functional EL-HN Fragment as a Potent Candidate Vaccine for the Prevention of Botulinum Neurotoxin Serotype E

Lu²,

Tan

et al. 2022

Toxins

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Clostridium botulinum produces 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. The EL-HN fragment (L and HN domains of BoNT/E) retained the enzymatic activity without in vivo neurotoxicity. Extensive investigations showed EL-HN functional fragment had the highest protective efficacy and contained some functional neutralizing epitopes. Further experiments demonstrated the EL-HN provided a superior protective effect compared with the EHc or EHc and EL-HN combination. Thus, the EL-HN played an important role in immune protection against BoNT/E and could provide an excellent platform for the design of botulinum vaccines and neutralizing antibodies. The EL-HN has the potential to replace EHc or toxoid as the optimal immunogen for the botulinum vaccine.

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Section: Discussionmentioning

confidence: 82%

Functional EL-HN Fragment as a Potent Candidate Vaccine for the Prevention of Botulinum Neurotoxin Serotype E

Lu²,

Tan

et al. 2022

Toxins

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“…Reports from other studies suggested that the induction of high titer antibodies might be a better indicator of protection than other parameters used for evaluation [ 29 , 30 ]. With regard to staphylococcal superantigen toxins, specific antibodies inhibiting T-cell activation are of great importance.…”

Section: Discussionmentioning

confidence: 99%

High Titer Persistent Neutralizing Antibodies Induced by TSST-1 Variant Vaccine Against Toxic Shock Cytokine Storm

Roetzer

Stich

Model

et al. 2020

Toxins

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Staphylococcal superantigen toxins lead to a devastating cytokine storm resulting in shock and multi-organ failure. We have previously assessed the safety and immunogenicity of a recombinant toxic shock syndrome toxin 1 variant vaccine (rTSST-1v) in clinical trials (NCT02971670 and NCT02340338). The current study assessed neutralizing antibody titers after repeated vaccination with escalating doses of rTSST-1v. At study entry, 23 out of 34 subjects (67.6%) had neutralizing antibody titers inhibiting T cell activation as determined by 3H-thymidine incorporation at a serum dilution of ≤1:100 with similar figures for inhibition of IL-2 activation (19 of 34 subjects, 55.9%) as assessed by quantitative PCR. After the first vaccination, numbers of subjects with neutralization titers inhibiting T cell activation (61.7% ≥ 1:1000) and inhibiting IL-2 gene induction (88.2% ≥ 1:1000) increased. The immune response was augmented after the second vaccination (inhibiting T cell activation: 78.8% ≥ 1:1000; inhibiting IL-2 induction: 93.9% ≥ 1:1000) corroborated with a third immunization months later in a small subgroup of subjects. Assessment of IFNγ, TNFα and IL-6 inhibition revealed similar results, whereas neutralization titers did not change in placebo participants. Antibody titer studies show that vaccination with rTSST-1v in subjects with no/low neutralizing antibodies can rapidly induce high titer neutralizing antibodies persisting over months.

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“…Purification and characterization of the recombinant Hc proteins of serotypes A, B and F have been completed, demonstrating good safety and efficacy against botulism. [23][24][25][26][27][28] In this study, we presented the production and evaluation of a recombinant non-His-tagged Hc subunit vaccine as a candidate subunit vaccine for human use against BoNT/E. The prokaryotic expression vector pTIG-Trx-EHc was successfully constructed.…”

Section: Discussionmentioning

confidence: 99%

Development and evaluation of candidate subunit vaccine and novel antitoxin against botulinum neurotoxin serotype E

Shi¹,

Liu

Mao³

et al. 2019

Human Vaccines & Immunotherapeutics

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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 Escherichia coli and purified by sequential chromatography. The immunogenicity of rEHc was evaluated in mice and doseand time-dependent immune responses were observed in both antibody titers and protective potency. Then, the pilot-scale expression and purification of rEHc were performed, and its immunological activity was characterized. Our results showed rEHc has good immunogenicity and can elicit strong protective potency against botulinum neurotoxin serotype E (BoNT/E) in mice, indicating that rEHc is an effective botulism vaccine candidate. Further, we developed a novel antitoxin against BoNT/E by purifying F(abʹ) 2 from pepsin-digested serum IgG of rEHc-inoculated horses. The protective effect of the F(abʹ) 2 antitoxin was determined in vitro and in vivo. The results showed that our F(abʹ) 2 antitoxin can prevent botulism in BoNT/E-challenged mice and effectively alleviate the progression of paralysis caused by BoNT/E to achieve therapeutic effects. Therefore, our results provide valuable experimental data for the production of a novel antitoxin, which is a promising candidate for the treatment of BoNT/E-induced botulism. ARTICLE HISTORY

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Development and evaluation of candidate subunit vaccine against botulinum neurotoxin serotype B

Cited by 13 publications

References 29 publications

Functional EL-HN Fragment as a Potent Candidate Vaccine for the Prevention of Botulinum Neurotoxin Serotype E

Functional EL-HN Fragment as a Potent Candidate Vaccine for the Prevention of Botulinum Neurotoxin Serotype E

High Titer Persistent Neutralizing Antibodies Induced by TSST-1 Variant Vaccine Against Toxic Shock Cytokine Storm

Development and evaluation of candidate subunit vaccine and novel antitoxin against botulinum neurotoxin serotype E

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