Maternal vaccination with pertussis vaccine containing only one immunity-stimulating component provides protection against disease in baboon model
Scientists at the U.S. Food and Drug Administration (FDA) demonstrated in a baboon model that vaccination during pregnancy with a mono-component pertussis vaccine comprised of pertussis toxoid alone was sufficient to protect newborn infants against pertussis disease (whooping cough).
Pertussis is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis. Persons with the infection have uncontrollable, violent coughing, sometimes followed by a “whooping” sound as they take a deep breath. It can affect persons of all ages, but is especially serious, and sometimes deadly, in babies less than two months old. Vaccination with the acellular pertussis (aP) vaccine (part of the combination DTaP vaccine that includes diphtheria and tetanus toxoids) starting at two months of age affords protection against pertussis. This leaves a window of vulnerability in the first months of life.
Currently available aP vaccines contain components designed to trigger immune responses against four proteins of B. pertussis, filamentous haemagglutinin (FHA), pertactin (PRN) fimbriae (FIM), and pertussis toxin (PTx). FHA, PRN, and FIM proteins enable the bacteria to attach to the lining of the upper respiratory tract. This enables the bacteria to cause disease and to spread to other individuals, for example, when the infected person coughs.
In a previous study using a baboon pertussis model, the FDA scientists found that vaccination of pregnant baboons with aP vaccines protected newborn baboons from disease when they were exposed to the bacteria at five weeks of age. However, despite this protection, maternal vaccination failed to reduce bacterial colonization of the infant upper respiratory tract. This suggested that the maternal antibodies generated by the vaccine against FHA, PRN, and FIM did not contribute to protecting the infant. Therefore, the scientists hypothesized that 1) it was the maternal, toxin-neutralizing anti-PTx antibodies generated by the vaccine that protected the infants; 2) a maternal vaccine containing only the PTx component would be sufficient to generate in mother baboons antibodies that would protect their infants following exposure to the bacteria.
In the current study, the scientists vaccinated pregnant baboon mothers with a vaccine containing only the PTx component. They then exposed infant baboons born to the vaccinated mothers to B. pertussis at five to six weeks of age. The study showed that pertussis bacteria colonized the upper respiratory tracts of both infants born to vaccinated mothers and those born to unvaccinated mothers. However, infant baboons born to unvaccinated mothers developed severe pertussis, while those born to vaccinated mothers showed no signs of disease. This showed that maternal vaccination with pertussis toxoid alone is sufficient to protect infant baboons from pertussis.
In addition, the results suggest that the most severe symptoms associated with pertussis are due to the action of pertussis toxin and can be blocked by the provision of toxin- neutralizing antibodies.
A potential benefit of these findings is that they might support development of maternal vaccines against pertussis that require only the PTx component. This might reduce the cost of producing the pertussis component of a combined diphtheria, tetanus and pertussis acellular maternal vaccine, thus facilitating its broader use internationally, in areas where medical diagnosis and care of infected infants is limited.
Title
Maternal Vaccination with a Mono-component Pertussis Toxoid Vaccine is Sufficient to Protect Infants in a Baboon Model of Whooping Cough
The Journal of Infectious Diseases
https://doi.org/10.1093/infdis/jiy022
15 January 2018
Authors
Kapil, Parul1; Papin, James F.2; Wolf, Roman F.3; Zimmerman, Lindsey I; Wagner, Leslie D.1; Merkel, Tod J.1
1Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
2Oklahoma Baboon Research Resource, Comparative Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
3Corresponding author: Tod J. Merkel, Laboratory of Respiratory and Special Pathogens/DBPAP/CBER/FDA 10903 New Hampshire Avenue, Silver Spring, MD 20903; [email protected]