Recombinant C fragment of botulinum neurotoxin B serotype (rBoNTB (HC)) immune response and protection in the rhesus monkey

Boles, James W.; West, Michael W.; Montgomery, Vicki A.; Tammariello, Ralph F.; Pitt, M. Louise M.; Gibbs, Paul; Smith, Leonard A.; LeClaire, Ross D.

doi:10.1016/j.toxicon.2006.02.013

Cited by 39 publications

(31 citation statements)

References 16 publications

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“…For this approach, we chose to evaluate a recombinant form of the nontoxic fragment of the C-terminal half of the H chain of Clostridium botulinum type A neurotoxin (BoHc/A) as a subunit vaccine candidate against botulism (12). It has been shown that systemic immunization of primates with a similar preparation of type B (BoHc/B) resulted in the generation of neutralizing Ab response (13). Because of the potential for botulinum neurotoxin to be disseminated by bioterrorists via airborne or oral routes and to result in a high mortality rate, it was classified as a category A agent by the U.S. Centers for Disease Control and Prevention.…”

Section: I-or 111mentioning

confidence: 99%

In Vivo Molecular Imaging Analysis of a Nasal Vaccine That Induces Protective Immunity against Botulism in Nonhuman Primates

Yuki

Nochi

Harada

et al. 2010

The Journal of Immunology

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Section: I-or 111mentioning

confidence: 99%

In Vivo Molecular Imaging Analysis of a Nasal Vaccine That Induces Protective Immunity against Botulism in Nonhuman Primates

Yuki

Nochi

Harada

et al. 2010

The Journal of Immunology

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“…The successful demonstration that C-fragment of tetanus toxin (TeNT) elicits protective immunity in animals has prompted the development of a new subunit vaccine against botulism [6,7]. Evaluation of the immunogenicity of different regions of BoNTs has confirmed that the C-fragment of the BoNTs elicits protective immunity in animals [8][9][10][11][12][13]. Therefore, subsequent efforts to develop vaccine candidates to protect against BoNTs forthwith may focus on the H C region of BoNTs [14].…”

Section: Introductionmentioning

confidence: 99%

Protective immunity against botulism provided by a single dose vaccination with an adenovirus-vectored vaccine

Zeng

Elias

et al. 2007

Vaccine

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Botulinum neurotoxins cause botulism, a neuroparalytic disease in humans and animals. We constructed a replication-incompetent adenovirus encoding a synthesized codon-optimized gene for expression of the heavy chain C-fragment (H C 50) of botulinum neurotoxin type C (BoNT/C). This recombinant human serotype 5 adenoviral vector (Ad5) was evaluated as a genetic vaccine candidate against botulism caused by BoNT/C in a mouse model. A one-time intramuscular injection with 10 5 to 2 × 10 7 pfu of adenoviral vectors elicited robust serum antibody responses against H C 50 of BoNT/C as assessed by ELISA. Immune sera showed high potency in neutralizing the active BoNT/ C in vitro. After a single dose of 2 × 10 7 pfu adenoviral vectors, the animals were completely protected against intraperitoneal challenge with 100 × MLD 50 of active BoNT/C. The protective immunity appeared to be vaccine dose-dependent. The anti-toxin protective immunity could last for at least 7 months without a booster injection. In addition, we observed that pre-existing immunity to the wild type Ad5 in the host had no significant influence on the protective efficacy of vaccination. The data suggest that an adenovirus-vectored genetic vaccine is a highly efficient prophylaxis candidate against botulism.

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“…However, as most of the expressed protein was insoluble in this system, subsequent studies have used the alternative host Pichia pastoris. Using this system, H C fragments of botulinum A, B, C, D, E, and F have been produced with satisfactory yields (15)(16)(17)(18)(19)(20). It is important to note, however, that P. pastoris is considered to be a less attractive host than E. coli for recombinant gene expression, from the perspectives of both genetic manipulation and production processes, and there is still an interest in improv-from the vector pET-9a (T7 promoter) were grown overnight at 37°C without induction.…”

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confidence: 99%

The Receptor Binding Domain of Botulinum Neurotoxin Serotype A (BoNT/A) Inhibits BoNT/A and BoNT/E Intoxications In Vivo

David

Diamant

Barnea

et al. 2013

Clin Vaccine Immunol

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The receptor binding domain of botulinum neurotoxin (BoNT), also designated the C terminus of the heavy chain (H C ), is a promising vaccine candidate against botulism. In this study, a highly efficient expression system for the protein was developed in Escherichia coli, which provided yields that were 1 order of magnitude higher than those reported to date (350 mg H C per liter). The product was highly immunogenic, protecting mice from a challenge with 10 5 50% lethal dose (LD 50 ) after a single vaccination and generating a neutralizing titer of 49.98 IU/ml after three immunizations. In addition, a single boost with H C increased neutralizing titers by up to 1 order of magnitude in rabbits hyperimmunized against toxoid. Moreover, we demonstrate here for the first time in vivo inhibition of BoNT/A intoxication by H C /A, presumably due to a blockade of the neurotoxin protein receptor SV2. Administration of H C /A delayed the time to death from 10.4 to 27.3 h in mice exposed to a lethal dose of BoNT/A (P ‫؍‬ 0.0005). Since BoNT/A and BoNT/E partially share SV2 isoforms as their protein receptors, the ability of H C /A to cross-inhibit BoNT/E intoxication was evaluated. The administration of H C /A together with BoNT/E led to 50% survival and significantly delayed the time to death for the nonsurviving mice (P ‫؍‬ 0.003). Furthermore, a combination of H C /A and a subprotective dose of antitoxin E fully protected mice against 850 mouse LD 50 of BoNT/E, suggesting complementary mechanisms of protection consisting of toxin neutralization by antibodies and receptor blocking by H C /A.

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Recombinant C fragment of botulinum neurotoxin B serotype (rBoNTB (HC)) immune response and protection in the rhesus monkey

Cited by 39 publications

References 16 publications

In Vivo Molecular Imaging Analysis of a Nasal Vaccine That Induces Protective Immunity against Botulism in Nonhuman Primates

In Vivo Molecular Imaging Analysis of a Nasal Vaccine That Induces Protective Immunity against Botulism in Nonhuman Primates

Protective immunity against botulism provided by a single dose vaccination with an adenovirus-vectored vaccine

The Receptor Binding Domain of Botulinum Neurotoxin Serotype A (BoNT/A) Inhibits BoNT/A and BoNT/E Intoxications In Vivo

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