Tolerability and Immunogenicity of a Single 40-µg Dose of Recombinant Botulinum Vaccine A/B (rBV A/B) for the Production of BabyBIG® in Volunteers With Existing Botulinum Immunity

This Phase 2, open-label, uncontrolled study designed to evaluate safety, tolerability, and immunogenicity of a single dose of rBV A/B in healthy participants previously immunized with pentavalent botulinum toxoid (or pentavalent botulinum toxoid and rBV A/B) for occupational protection will be conducted to collect source plasma for potential use in the production of BabyBIG and to evaluate safety and immunogenicity of the vaccine in these participants over a 12-week period, with a follow-up safety assessment at 6 months.

Start Date09 Jul 2024

Sponsor / Collaborator

California Department of Public Health

NCT00004401 / CompletedNot ApplicableIIT

Study of Human Botulism Immunoglobulin in Infants With Botulism

OBJECTIVES: I. Determine the safety of human botulism immune globulin (BIG) in patients with infant botulism by monitoring side effects (e.g., rash, fever, hypotension, and anaphylaxis).
II. Assess the efficacy of BIG in these patients by monitoring disease severity, incidence of complications (respiratory arrest, aspiration, pneumonia, etc.), and length of hospital stay.

Start Date01 Jan 1998

Sponsor / Collaborator

California Department of Health Services

100 Clinical Results associated with Botulism Immune Globulin(Human)(California Department of Public Health)

100 Translational Medicine associated with Botulism Immune Globulin(Human)(California Department of Public Health)

100 Patents (Medical) associated with Botulism Immune Globulin(Human)(California Department of Public Health)

Literatures (Medical) associated with Botulism Immune Globulin(Human)(California Department of Public Health)

31 Dec 2024·Human Vaccines & Immunotherapeutics

Production of monoclonal antibodies against botulinum neurotoxin in Nicotiana benthamiana

Article

Author: Bulaon, Christine Joy I ; Jirarojwattana, Perawat ; Sangprasat, Kornchanok ; Wongwatanasin, Apidsada ; Rattanapisit, Kaewta ; Srisangsung, Theerakarn ; Phoolcharoen, Waranyoo

Botulism is a fatal neurologic disease caused by the botulinum toxin (BoNT) produced by Clostridium botulinum. It is a rare but highly toxic disease with symptoms, such as cramps, nausea, vomiting, diarrhea, dysphagia, respiratory failure, muscle weakness, and even death. Currently, two types of antitoxin are used: equine-derived heptavalent antitoxin and human-derived immunoglobulin (BabyBIG®). However, heptavalent treatment may result in hypersensitivity, whereas BabyBIG®, has a low yield. The present study focused on the development of three anti-BoNT monoclonal antibodies (mAbs), 1B18, C25, and M2, in Nicotiana benthamiana. The plant-expressed mAbs were purified and examined for size, purity and integrity by SDS-PAGE, western blotting and size-exclusion chromatography. Analysis showed that plant-produced anti-BoNT mAbs can fully assemble in plants, can be purified in a single purification step, and mostly remain as monomeric proteins. The efficiency of anti-BoNT mAbs binding to BoNT/A and B was then tested. Plant-produced 1B18 retained its ability to recognize both mBoNT/A1 and ciBoNT/B1. At the same time, the binding specificities of two other mAbs were determined: C25 for mBoNT/A1 and M2 for ciBoNT/B1. In conclusion, our results confirm the use of plants as an alternative platform for the production of anti-BoNT mAbs. This plant-based technology will serve as a versatile system for the development botulism immunotherapeutics.

01 Jul 2023·Journal of education & teaching in emergency medicine

Infant Botulism.

Article

Author: Garispe, Ashley ; Cherry, Steven

AudienceThis oral board case is appropriate for emergency medicine residents and medical students (with senior resident assistance) on emergency medicine rotation.IntroductionAlthough a somewhat rare disease, infant botulism is a true pediatric emergency that carried a 90% rate of mortality prior to the development of an antitoxin.1 While botulism infections can be iatrogenic, foodborne, or involve infected wounds, infant botulism remains the most common presentation of this disease and accounts for approximately 70% of new cases annually.2 Caused by Clostridium botulinum, the inactive spores are ingested by the infant and germinate in the large intestine.3,4 The resulting neurotoxin prevents the release of acetylcholine at the presynaptic membrane which results in flaccid paralysis. Classically, the bulbar musculature is affected before somatic muscular, which results in the typical presentation of "descending paralysis."2,5 While confirmatory testing is important, it is often delayed by more than 24 hours, making both clinical recognition and implementation of treatment before confirmatory testing of vital importance.6,7 Treatment consists of providing airway, nutritional, and hydration support in addition to administering botulinum-specific antitoxin.8,9 While patients over the age of 12 months are treated with equine botulinum antitoxin, the Food and Drug Administration (FDA) has approved a human-derived immunoglobulin treatment, Botulism Immune Globulin Intravenous (BIG-IV, ie, "Baby BIG") for pediatric patients less than 12 months of age.1,2,6 Ordering BIG-IV is a complex and multidisciplinary process, requiring the treating physician to discuss any suspicious case with the Infant Botulism Treatment and Prevention Program (IBTPP) which is a branch of the California Department of Public Health.6 With early recognition and implementation of treatment, most infants will make a full recovery.Educational ObjectivesAt the end of this oral board session, examinees will: 1) demonstrate an ability to obtain a complete pediatric medical history, 2) perform an appropriate physical exam on a pediatric patient, 3) investigate a broad differential diagnosis for neuromuscular weakness in a pediatric patient, 4) recognize the classic presentation of infant botulism and implement treatment with botulinum specific antitoxin before confirmatory testing, 5) recognize impending airway failure and intubate the pediatric patient with appropriately dosed medications and ET tube size, and 6) demonstrate effective communication with healthcare team members and parents.Educational MethodsThis oral board case followed the standard American Board of Emergency Medicine-style case in a tertiary care hospital with access to all specialists and resources needed. This case was tested using 12 resident volunteers ranging from PGY 1-2 in an ACGME (Accreditation Council for Graduate Medical Education) accredited emergency medicine residency program. Learners were debriefed immediately after the case and were given the opportunity to provide feedback.Research MethodsThe learners participating in the oral board case provided immediate feedback both by verbal discussion and via a written survey requiring them to rate the efficacy of the exercise. The efficacy of the educational content was assessed by comparing scoring measures of the ACGME core competencies across all learners based on post graduate year (PGY). Scoring measures were determined using a scale from 1-8, with 1-4 being unacceptable performance and 5-8 being acceptable. Efficacy required full completion of the oral board case by the residents as well as a debriefing session during which key educational concepts were discussed.ResultsThe practice oral board candidates consisted of 7 PGY1 and 5 PGY2 level residents. The average score of participating residents for each training level was PGY1: 4.5 and PGY2: 5.7. All except for 2 PGY2 residents missed at least one critical action with the majority of PGY1 residents missing more than one critical action for the case. All participating residents rated the educational value of the case as 4.75 (1-5 Likert scale, with 5 being excellent).DiscussionThe educational content of this oral board case and debriefing session were effective for teaching the presentation, evaluation, and appropriate management of infant botulism. Infant botulism is a true pediatric emergency and prompt recognition and treatment is imperative in order to decrease mortality. While mortality was approximately 90% one hundred years ago, today infant botulism carries a much better prognosis due to the advent of antitoxin treatment with a mortality closer to 15%.1 This case highlights several classic physical exam findings including bulbar findings in addition to somatic weakness. Additionally, this case requires definitive airway management with endotracheal intubation, which is true for approximately 50% of infants with botulism.1 While a stool culture or direct toxin assay of the gastric contents, serum, or stool should be performed to confirm the diagnosis, these tests are often performed by the state health department or the Centers for Disease Control (CDC) and often take up to five days to result, during which time the patient will continue to deteriorate. Therefore, the treating physician should seek emergent consultation with the IBTPP to help facilitate the multidisciplinary decision to initiate treatment with human-derived anti-botulinum toxin antibodies.6 If the IBTPP deems that infant botulism is highly suspected based on the history and physical exam, then appropriate treatment should not be delayed and BIG-IV should be administered.6, 7 With early recognition and implementation of treatment, most infants will make a full recovery within several months to a year. Upon discharge, patients will likely require outpatient neurology follow-up in addition to physical therapy to aid in recovery. Because infant botulism is a true pediatric emergency with potentially high mortality, reaching the appropriate diagnosis expeditiously will allow the emergency physician to communicate effectively with worried parents regarding the disease progression and facilitate correct treatment early in order to prevent significant sequela.TopicsPediatric weakness, pediatric neurotoxin, infant botulism, neuromuscular weakness.

01 Apr 2022·Journal of education & teaching in emergency medicine

Infant Botulism.

Article

Author: Morris, Victoria ; Stevens, Gowri ; Wilson, Jessica ; Wians, Robert

AudienceEmergency medicine and pediatric residents, and pediatric emergency medicine (PEM) fellows.IntroductionBotulism is a rare but serious cause of infant hypotonia, vomiting, and respiratory failure. The differential diagnosis and management of a hypotonic infant with progressive weakness leading to respiratory failure is a rare presentation with high morbidity and mortality.1 Infants with botulism generally present with vague complaints that progressively worsen over time.2 Recognition of descending paralysis in an infant as well as signs of respiratory failure are key to preventing an adverse outcome. A key component of botulism treatment is recognizing the need to mobilize local resources to obtain BabyBIG^® (botulism immune globulin). This process can and should begin in the emergency department.Educational ObjectivesAfter this simulation learners should be able to: 1) develop a differential diagnosis for the hypotonic infant, 2) recognize signs and symptoms of infant botulism, 3) recognize respiratory failure and secure the airway with appropriate rapid sequence intubation (RSI) medications, 4) initiate definitive treatment of infant botulism by mobilizing resources to obtain antitoxin, 5) continue supportive management and admit the patient to the pediatric intensive care unit (PICU), 6) understand the pathophysiology and epidemiology of infant botulism, 7) develop communication and leadership skills when evaluating and managing critically ill infants.Educational MethodsThis simulation case was performed using a high-fidelity Laerdal SimBaby with intubating capabilities and real-time vital sign monitoring. Additionally, this case can be performed with low fidelity manikins with supplemental scripting and visual stimuli. With minor adjustments, this case could be modified into an oral boards case.Research MethodsWe obtained feedback from a convenience sample of random participants after the simulation case and debrief were completed. The sample of emergency medicine residents (N=21) and PEM fellow (N=1) completed 5 questions on a 5-point Likert scale.ResultsThe emergency medicine residents and PEM fellow had mostly favorable feedback regarding the simulation and debriefing. Most strongly agreed or agreed that this would improve their performance in an actual clinical setting.DiscussionInfant botulism is a rare condition, presenting as vague non-specific complaints that worsen over time. It is important to differentiate infant botulism from other causes of weakness, hypotonia, and respiratory failure. This case presents learners with a high acuity, rare case of infant botulism and allows them to work through a complex pediatric patient encounter in a psychologically safe space. The presence of a standardized patient to play the patient's parent is key to assess learners' nontechnical communication skills and to increase fidelity during the simulation.TopicsInfant botulism, pediatric emergency medicine, respiratory failure, hypotonia, toxicology.

100 Deals associated with Botulism Immune Globulin(Human)(California Department of Public Health)

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Indication	Country/Location	Organization	Date
Botulism	US	California Department of Public Health	23 Oct 2003
Botulism	US	California Department of Health Services	23 Oct 2003

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