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Antibody Providers

Development of monoclonal and polyclonal antibody-based botulinum neurotoxin vaccines and antitoxins for prophylaxis and postexposure treatment is a high biodefense priority. BoNT antibodies for serotypes A to F isolated from a number of organisms are commercially available. Antitoxins are currently available in the United States from the CDC. Vaccines, including monovalent, trivalent, pentavalent, and heptavalent toxoids are under development.

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Antibodies in Current Research

Antibodies reported in current research involving the study of antibodies to neutralize botulinum neurotoxins are presented with associated study information including antibody name, neutralizing activity, reactive component, experimental applications, immunoglobulin type, immunoglobulin isotype and publication. Additional details are presented here describing these key terms.

Neutralizing Activity
Yes = the antibody neutralizes specified serotype neurotoxin in vivo or in vitro
No = the antibody does not neutralize specified serotype neurotoxin
Blank, Null = no data available

Reactive Component (the component of the botulinum neurotoxin that binds to the antibody)
HA1, HA2, or HA3b = subcomponent of hemagglutinin
Hc = heavy chain
HC or H2 = C-terminal of heavy chain
HN or H1 = N-terminal of heavy chain
Lc = light chain

Experimental Applications
DB = Dot Blotting
ELISA = Enzyme Linked Immunosorbent Assay
IP = Immunoprecipitation
WB = Western Blotting or Immunoblotting

Immunoglobulin Type
monoclonal
polyclonal

Immunoglobulin Isotype
IgG1 or IgG2 = subclass of IgG
k = kappa
scFv = single chain variable fragment

Antibody
Name
Neutralizing
Activity
Reactive
Component
Experimental
Applications
Immunoglobulin
Type
Immunoglobulin
Isotype
PubMed ID
BT57-1 Yes BoNT/A Lc WB monoclonal IgG1 PMID: 11425742
BT150-3 Yes BoNT/A Hc WB monoclonal IgG1 PMID: 11425742
S25 Yes BoNT/A Hc ELISA monoclonal IgG1k PMID: 11553596
C25 Yes BoNT/A Hc ELISA monoclonal IgG1k PMID: 11553596
3D12 Yes BoNT/A Hc ELISA, WB monoclonal IgG1k PMID: 11553596
CHA1-489 Yes BoNT/C HA1 ELISA, WB monoclonal IgG2ak PMID: 11926732
CHA1-394 Yes BoNT/C HA1 ELISA, WB monoclonal IgG2bk PMID: 11926732
CHA1-28 No BoNT/C HA1 ELISA, WB monoclonal IgGk PMID: 11926732
CHA1-15 BoNT/C HA1 ELISA monoclonal IgG1k PMID: 11926732
CHA1-23 Yes BoNT/C HA1 ELISA monoclonal IgG1k PMID: 11926732
CHA1-29 Yes BoNT/C HA1 ELISA monoclonal IgG2bk PMID: 11926732
CHA1-54 Yes BoNT/C HA1 ELISA monoclonal IgG1k PMID: 11926732
CHA3b-62 BoNT/C HA3b ELISA, WB monoclonal IgG1k PMID: 11926732
CHA3b-6 No BoNT/C HA3b ELISA, WB monoclonal IgG2bk PMID: 11926732
CHA3b-12 No BoNT/C HA3b ELISA, WB monoclonal IgG1k PMID: 11926732
CHA2-14 No BoNT/C HA2 ELISA, WB monoclonal IgG1k PMID: 11926732
BTBH-N1 Yes BoNT/B HN ELISA, WB monoclonal IgG1k PMID: 15225558
LE15-5 Yes BoNT/E Hc WB monoclonal IgG1k PMID: 2450068
LE34-6 Yes BoNT/E Hc WB monoclonal IgG1k PMID: 2450068
EK18-2 No BoNT/E Hc WB monoclonal IgG1k PMID: 2450068
EK19-7 Yes BoNT/E Hc WB monoclonal IgG1k PMID: 2450068
EK21-4 Yes BoNT/E Hc WB monoclonal IgG1k PMID: 2450068
AE27-9 Yes BoNT/E Hc WB monoclonal IgG1k PMID: 2450068
EL161-38 No Lc of BoNT/E, BoNT/B,
BoNT/CI, BoNT/D, tetanus
DB, ELISA, WB monoclonal IgG1k PMID: 2450068
EL211-3 No BoNT/E Lc WB monoclonal IgG1k PMID: 2450068
EL219-15 No BoNT/E Lc WB monoclonal IgG1k PMID: 2450068
C-9 No BoNT/C Hc ELISA monoclonal IgG1k PMID: 2581939
CA-12 Yes BoNT/C Hc ELISA monoclonal IgG1k PMID: 2581939
C-14 No BoNT/C Hc ELISA monoclonal IgG1k PMID: 6183207
C-17 Yes BoNT/C Hc ELISA monoclonal IgG1k PMID: 6183207
3A6 Yes BoNT/A Hc ELISA monoclonal scFv PMID: 11858873
2A1 Yes BoNT/A Hc ELISA monoclonal scFv PMID: 11858873
3B8 No BoNT/A Hc ELISA monoclonal scFv PMID: 11858873
3F10 No BoNT/A Hc ELISA monoclonal scFv PMID: 11858873
2B11 No BoNT/A HN ELISA monoclonal scFv PMID: 11858873
3D4 No BoNT/A HN ELISA monoclonal scFv PMID: 11858873
3A11 No BoNT/A HN ELISA monoclonal scFv PMID: 11858873
4A4 No BoNT/A HN ELISA monoclonal scFv PMID: 11858873
3G4 No BoNT/A HN ELISA monoclonal scFv PMID: 11858873
6B2-2 Yes BoNT/A Hc ELISA, IP, WB monoclonal IgG1 PMID: 9795391
6C2-4 Yes BoNT/A Hc ELISA, IP, WB monoclonal IgG1 PMID: 9795391
4A2-2 Yes BoNT/A H2 ELISA, IP, WB monoclonal IgG2a PMID: 9795391
6E10-10 Yes BoNT/A Hc ELISA, IP, WB monoclonal IgG2a PMID: 9795391
6E9-12 Yes BoNT/A H2 ELISA, IP, WB monoclonal PMID: 9795391
6C2-2 Yes BoNT/A H2 ELISA, IP, WB monoclonal PMID: 9795391
N-C-45 No ELISA monoclonal PMID: 6198281
N-C-109 Yes ELISA monoclonal PMID: 6198281
D-26 No BoNT/D Hc ELISA monoclonal PMID: 6198281
D34 No BoNT/D Hc ELISA monoclonal PMID: 6198281
N-D-6 No BoNT/D Hc ELISA monoclonal PMID: 6198281
D-162 Yes BoNT/D Hc ELISA monoclonal PMID: 6198281
D-210 Yes BoNT/D Hc ELISA monoclonal PMID: 6198281
D-28 Yes BoNT/D Hc ELISA monoclonal PMID: 6198281
N-D-1 Yes BoNT/D Hc ELISA monoclonal PMID: 6198281
N-D-2 Yes BoNT/D Hc ELISA monoclonal PMID: 6198281
N-A-70 Yes ELISA monoclonal PMID: 6198281
N-A-145 Yes ELISA monoclonal PMID: 6198281
CA-12 Yes Hc of BoNT/C and BoNT/D ELISA monoclonal PMID: 6198281
N-CA-137 Yes Hc of BoNT/C and BoNT/D ELISA monoclonal PMID: 6198281
N-CA-11 Yes Hc of BoNT/C and BoNT/D ELISA monoclonal PMID: 6198281
N-CA-27 Yes Hc of BoNT/C and BoNT/D ELISA monoclonal PMID: 6198281
N-DA-20 No ELISA monoclonal PMID: 6198281
N-DA-75 Yes BoNT/D Lc ELISA monoclonal PMID: 6198281
N-DA-122 Yes BoNT/D Lc ELISA monoclonal PMID: 6198281
CDA-69 Yes Hc of BoNT/C and BoNT/D ELISA monoclonal PMID: 6198281
N-CDA-14 Yes Hc of BoNT/C and BoNT/D ELISA monoclonal PMID: 6198281
N-CDA-175 No Hc of BoNT/C and BoNT/D ELISA monoclonal PMID: 6198281
CDA-30 No Lc of BoNT/C and BoNT/D ELISA monoclonal PMID: 6198281
N-CDA-5 No Lc of BoNT/C and BoNT/D ELISA monoclonal PMID: 6198281
N-CDA-135 No Lc of BoNT/C and BoNT/D ELISA monoclonal PMID: 6198281
anti-C-ST Yes polyclonal PMID: 6198281
anti-C-ST-Hc Yes BoNT/C Hc polyclonal PMID: 6198281
anti-C-ST-Lc Yes BoNT/C Lc polyclonal PMID: 6198281
anti-D-1873 Yes polyclonal PMID: 6198281
anti-D-1873-Hc Yes BoNT/D Hc polyclonal PMID: 6198281
anti-D-1873-Lc Yes BoNT/D Lc polyclonal PMID: 6198281
anti-D-SA Yes polyclonal PMID: 6198281
A101 Yes BoNT/A H2 ELISA, WB monoclonal PMID: 8577267
A102 No BoNT/A H1 ELISA, WB monoclonal PMID: 8577267
A108 Yes BoNT/A H1 ELISA, WB monoclonal PMID: 8577267
A109 Yes BoNT/A Lc ELISA, WB monoclonal PMID: 8577267
A115 Yes BoNT/A Lc ELISA, WB monoclonal PMID: 8577267
A116 Yes BoNT/A H1 ELISA, WB monoclonal PMID: 8577267
A119 Yes BoNT/A H1 ELISA, WB monoclonal PMID: 8577267
A122 Yes BoNT/A Lc ELISA, WB monoclonal PMID: 8577267
A123 Yes BoNT/A H1 ELISA, WB monoclonal PMID: 8577267
A124 Yes BoNT/A H1 ELISA, WB monoclonal PMID: 8577267
A125 Yes BoNT/A H2 ELISA, WB monoclonal PMID: 8577267
AI-3 Yes BoNT/A H1 ELISA, WB monoclonal PMID: 8577267
AI-6 Yes BoNT/A H2 ELISA, WB monoclonal PMID: 8577267
A1-13 Yes BoNT/A ELISA, WB monoclonal PMID: 8577267
A1-15 Yes BoNT/A ELISA, WB monoclonal PMID: 8577267
A1-16 Yes BoNT/A Lc ELISA, WB monoclonal PMID: 8577267
A1-17 Yes BoNT/A H1 ELISA, WB monoclonal PMID: 8577267
E14 No BoNT/E H1 monoclonal IgG1 PMID: 2423459
E16 Yes BoNT/E H2 ELISA, WB monoclonal IgG2b PMID: 2423459
E17 No BoNT/E H2 ELISA, WB monoclonal IgG1 PMID: 2423459
E19 Yes BoNT/E H1 ELISA, WB monoclonal IgG1 PMID: 2423459
E22 No BoNT/E H1 ELISA, WB monoclonal IgG1 PMID: 2423459
E30 Yes BoNT/E Lc ELISA, WB monoclonal IgG1 PMID: 2423459
B4 No BoNT/A Hc ELISA monoclonal IgG1k PMID: 16113261
9D8 No BoNT/A HN ELISA monoclonal IgG1k PMID: 16113261
7C1 No BoNT/A Lc ELISA monoclonal IgG1k PMID: 16113261
3a6 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
3d4 ELISA monoclonal scFv PMID: 9125539
4a4 ELISA monoclonal scFv PMID: 9125539
3a2 ELISA monoclonal scFv PMID: 9125539
3e3 ELISA monoclonal scFv PMID: 9125539
3e8 ELISA monoclonal scFv PMID: 9125539
3a11 ELISA monoclonal scFv PMID: 9125539
3e7 ELISA monoclonal scFv PMID: 9125539
3h3 ELISA monoclonal scFv PMID: 9125539
3a1 ELISA monoclonal scFv PMID: 9125539
w3 ELISA monoclonal scFv PMID: 9125539
w42 ELISA monoclonal scFv PMID: 9125539
g23 ELISA monoclonal scFv PMID: 9125539
g3 ELISA monoclonal scFv PMID: 9125539
g11 ELISA monoclonal scFv PMID: 9125539
w7 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
w9 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
g7 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
w20 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
w36 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
w43 ELISA monoclonal scFv PMID: 9125539
g53 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
g57 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
c9 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
c15 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
3f6 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
2a2 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
2b10 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
2b1 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
3e6 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
2e6 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
3d1 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
2b6 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
2h6 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
2a8 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
id5 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
ie8 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
ig7 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
3c3 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
2c3 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
3e2 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
3c5 BoNT/A Hc ELISA monoclonal scFv PMID: 9125539
4A2-4 Yes BoNT/A Hc ELISA, IP, WB monoclonal IgG2a PMID: 11119555
6E9-1 Yes BoNT/A Hc ELISA, IP, WB monoclonal IgG2a PMID: 11119555
6E9-3 Yes BoNT/A Hc ELISA, IP, WB monoclonal IgG2a PMID: 11119555
6E9-4 Yes BoNT/A Hc ELISA, IP, WB monoclonal IgG2a PMID: 11119555
6E10-4 Yes BoNT/A Hc ELISA, IP, WB monoclonal IgG2a PMID: 11119555
6E10-5 Yes BoNT/A Hc ELISA, IP, WB monoclonal IgG2a PMID: 11119555
6E10-8 Yes BoNT/A Hc ELISA, IP, WB monoclonal IgG2a PMID: 11119555

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Antitoxins

Currently, the main treatment for human botulism is the administration of botulinum neurotoxin antitoxin to neutralize the unbound circulating toxin. Antitoxin treatment is most effective in reducing the severity of symptoms if administered in the first 24 hours post exposure. Skin tests for horse serum sensitivity prior to treatment are needed for the equine derived antitoxins.

Therapeutic and prophylactic immunobiologics products distributed by the CDC can be found at the CDC Drug Service Formulary. Physicians can contact the CDC for antitoxins at: 770-488-7100 (24-hour emergency number). Human-derived botulism immune globulin (BIG) for the treatment of infant botulism is available by contacting the California Department of Health Services (24-hour telephone: 510-540-2646). To learn more, visit the California Department of Health Services Infant Botulism Treatment & Prevention Program or view the Infant Botulism Chapter from the Textbook of Pediatric Infectious Disease, 4th Edition.


Antitoxin
Source
Type
Source or Reference
Status
bivalent equine A, B CDC Botulism Handbook  picture of PDF Licensed
Botulism Immune Globulin Intravenous (BabyBIG or BIG-IV) human A, B PMID: 16452558  picture of PDF Licensed
despeciated heptavalent botulism immune globulin (dBIG) equine A, B, C, D, E, F, G PMID: 8842274 Investigational New Drug
monovalent equine E CDC Drug Service Formulary Type E Investigational New Drug
quadrivalent A, B, E, F CDC MMWR April 21, 2006/55(15);434
recombinant     Medscape Infectious Disease Preclinical
trivalent equine A, B, E CDC Botulism Handbook  picture of PDF Licensed


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Synthetic Antibodies

Synthetic antibodies are obtained from phage display, a new technique used to develop antibodies with target-recognition qualities of natural antibodies. Single-chain variable fragment (scFv) phage antibodies are presented with PubMed ID and Protein Accession.


Synthetic Antibody
PubMed ID
Protein Accession
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26550
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26549
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26548
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26546
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26545
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26544
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26543
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26542
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26541
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26540
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26539
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26538
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26537
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26536
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26535
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26534
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26533
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26532
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26531
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26530
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26547
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26528
Anti BoNT/A Hc scFv Antibody PMID: 9284147 AAC26529
scFv Antibody V-region PMID: 11858873 AAC98378
2A1 scFv Antibody V-region mRNA PMID: 11858873 AF090405
3F6 scFv Antibody V-region mRNA PMID: 11858873 AF090420
3H4 Anti BoNT/A Hc scFv Antibody PMID: 9284147 AF003702
S25 Anti BoNT/A Hc scFv Antibody PMID: 9284147 AF003725

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Vaccines

Botulism vaccine work began in the 1940s. Individuals considered to be at risk of exposure to botulism, such as laboratory and military personnel, are currently vaccinated. At this time, a pentavalent (A-E) BoNT toxoid vaccine and a monovalent (F) vaccine are available under Investigational New Drugs (IND) status from the CDC. Toxoid and recombinant botulinum vaccines are under development with the aim of providing protection against the seven serotypes of botulism.


Vaccine
Type
Reference/ PubMed ID
Status
BoNToxoid/A A PMID: 15699151 mucosal immunization
bivalent C, D Department of Primary Industries and Fisheries, Queensland Available
BT-VACC multivalent DOR BioPharma, Inc. Under development (successful in animals)
monovalent F PMID: 11086225 Investigational New Drug
multivalent multivalent Cambridge Biostability Under development
pentavalent (PBT) A, B, C, D, E PMID: 11086225 Investigational New Drug
recombinant (rBV A/B) A, B DVC JVAP (DOD) Phase I: Initial safety trial
recombinant C, D, E, G DVC JVAP (DOD) Under development
recombinant A, B, C, E, F Medscape Clinical trials
recombinant D, G Medscape Clinical trials
recombinant bivalent (rBOT) A, B Emergent BioSolutions Pre-clinical

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Vaccine Development Strategies

Current research efforts are focused on the production of nontoxic recombinant proteins or vectored vaccines to obtain recombinant vaccines. The vaccine development strategies listed below are geared to eliminate the need to treat BoNT toxin with formalin and allow a high level of toxin production (Dertzbaugh MT and MW West 1996, PMID: 9014296).

  • DNA-based Vaccines:

  • Recombinant Heavy Chain (Hc) Proteins:

    • Arimitsu H et al. 2004: Vaccination with recombinant whole heavy chain fragments of Clostridium botulinum Type C and D neurotoxins  picture of PDF
    • Bryne MP et al. 2000: Development of vaccines for prevention of botulism
    • Clayton MA et al. 1995: Protective vaccination with a recombinant fragment of Clostridium botulinum neurotoxin serotype A expressed from a synthetic gene in Escherichia coli  picture of PDF
  • Venezuelan Equine Encephalitis (VEE) Virus Vector System:

    • Lee JS et al. 2001: Candidate Vaccine against Botulinum Neurotoxin Serotype A Derived from a Venezuelan Equine Encephalitis (VEE) Virus Vector System  picture of PDF
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