Maternal Vaccination With a Monocomponent Pertussis Toxoid Vaccine Is Sufficient to Protect Infants in a Baboon Model of Whooping Cough

Kapil, Parul; Papin, James F.; Wolf, Roman F.; Zimmerman, Lindsey I.; Wagner, Leslie; Merkel, Tod J.

doi:10.1093/infdis/jiy022

Cited by 38 publications

(35 citation statements)

References 30 publications

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“…These results are similar to ours in that only animals with high total anti-PTx titers exhibited enhanced survival, suppressed leukocytosis, and normal clinical signs. A ~3-fold increase in maximum leukocytosis was observed (38), which is similar to the transient ~2-fold increase observed here (Fig. 4 and fig.…”

Section: Discussionsupporting

confidence: 88%

Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons

et al. 2020

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Pertussis continues to cause considerable infant mortality world-wide, which could be addressed in part by passive immunization strategies. Antibody hu1B7 is a candidate therapeutic that potently neutralizes pertussis toxin in vitro, prevents leukocytosis in mice and treats established disease in weanling baboons as part of an antibody cocktail. Here, we evaluated the potential for hu1B7 and an extended half-life hu1B7 variant to prevent death, leukocytosis and other clinical symptoms in a newborn baboon model that mimics many aspects of human disease. We administered a single antibody dose to newborn baboons five weeks prior to experimental infection. While all animals were heavily colonized with Bordetella pertussis, prophylaxed animals showed significantly greater survival (P < 0.005), delayed and suppressed leukocytosis (P < 0.01) and enhanced clinical outcomes, including coughing (P < 0.01), as compared to controls. Together, this work demonstrates that a single neutralizing anti-PTx antibody is sufficient to prevent clinical pertussis symptoms.

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Section: Discussionsupporting

confidence: 88%

Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons

et al. 2020

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“…Non-human primates are the best and most accurate animal model of human infection [85][86][87][88][89][90][91][92][93] and are often used in preclinical trials [122]. Similar to companion animals, non-human primates are also USDA protected, although the approvals and protocol requirements differ.…”

Section: Animal Modelsmentioning

confidence: 99%

“…Vaccination studies are commonly done in mice [40,42,49], rabbits [65,66], cattle [81], and primates [86,91,93]. These studies can demonstrate the power of inhibiting the T3SS by using antibodies that recognize T3SS effectors or structural components.…”

Section: Vaccines and Immunizationsmentioning

confidence: 99%

“…Maternal vaccination is a variation of the typical vaccine or immunization assay. The Merkel laboratory used baboon females that were pregnant and immunized them with a vaccine for B. pertussis [86]. They then waited until the infant baboons were born and performed antibody testing on the infants to determine how effective the vaccine was at transmitting from the mother to child, either in the womb pre-birth or via nursing post-birth.…”

Section: Maternal Vaccinationmentioning

confidence: 99%

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Animal Models of Type III Secretion System-Mediated Pathogenesis

Hotinger

May

2019

Pathogens

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The type III secretion system (T3SS) is a conserved virulence factor used by many Gram-negative pathogenic bacteria and has become an important target for anti-virulence drugs. Most T3SS inhibitors to date have been discovered using in vitro screening assays. Pharmacokinetics and other important characteristics of pharmaceuticals cannot be determined with in vitro assays alone. In vivo assays are required to study pathogens in their natural environment and are an important step in the development of new drugs and vaccines. Animal models are also required to understand whether T3SS inhibition will enable the host to clear the infection. This review covers selected animal models (mouse, rat, guinea pig, rabbit, cat, dog, pig, cattle, primates, chicken, zebrafish, nematode, wax moth, flea, fly, and amoeba), where T3SS activity and infectivity have been studied in relation to specific pathogens (Escherichia coli, Salmonella spp., Pseudomonas spp., Shigella spp., Bordetella spp., Vibrio spp., Chlamydia spp., and Yersinia spp.). These assays may be appropriate for those researching T3SS inhibition.

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“…As in humans, the disease demonstrates agerelated differences in severity. Five-to 6-week-old (infant) baboons experience very severe disease upon infection, often requiring euthanasia (12,13). In contrast, 6-to 9-month-old (juvenile) baboons experience severe disease that lasts approximately 2 weeks, followed by a 2-to 3-week convalescence, resulting in a return to full health (10).…”

mentioning

confidence: 99%

Histopathology of Bordetella pertussis in the Baboon Model

et al. 2018

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Pertussis is a severe respiratory disease caused by The classic symptoms of pertussis include paroxysmal coughing with an inspiratory whoop, posttussive vomiting, cyanosis, and persistent coryzal symptoms. Infants under 2 months of age experience more severe disease, with most deaths occurring in this age group. Most of what is known about the pathology of pertussis in humans is from the evaluation of fatal human infant cases. The baboon model of pertussis provides the opportunity to evaluate the histopathology of severe but nonfatal pertussis. The baboon model recapitulates the characteristic clinical signs of pertussis observed in humans, including leukocytosis, paroxysmal coughing, mucus production, heavy colonization of the airway, and transmission of the bacteria between hosts. As in humans, baboons demonstrate age-related differences in clinical presentation, with younger animals experiencing more severe disease. We examined the histopathology of 5- to 6-week-old baboons, with the findings being similar to those reported for fatal human infant cases. In juvenile baboons, we found that the disease is highly inflammatory and concentrated to the lungs with signs of disease that would typically be diagnosed as acute respiratory distress syndrome (ARDS) and bronchopneumonia. In contrast, no significant pathology was observed in the trachea. Histopathological changes in the trachea were limited to cellular infiltrates and mucus production. Immunohistostaining revealed that the bacteria were localized to the surface of the ciliated epithelium in the conducting airways. Our observations provide important insights into the pathology of pertussis in typical, severe but nonfatal pertussis cases in a very relevant animal model.

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Maternal Vaccination With a Monocomponent Pertussis Toxoid Vaccine Is Sufficient to Protect Infants in a Baboon Model of Whooping Cough

Abstract: Our results demonstrated that maternal vaccination with a PTx-only vaccine is sufficient to protect newborn baboons from disease following exposure to pertussis.

Cited by 38 publications

References 30 publications

Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons

Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons

Animal Models of Type III Secretion System-Mediated Pathogenesis

Histopathology of Bordetella pertussis in the Baboon Model

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