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Partnering against pertussis
AUSTIN, Texas—Pertussis, the highly contagious respiratory tract infection also known as whooping cough, affects 16 million infants around the world annually, causing an estimated 200,000 child deaths every year. According to the U.S. Centers for Disease Control and Prevention, the disease continues to be a major cause of infant death in developing nations.
While childhood vaccinations largely prevent the disease in the United States, there has been increased prevalence in the last decade. Reasons for the resurgence may include parents’ reluctance to vaccinate their children and a changed vaccine that provides less immunity.
A team of researchers from the University of Texas at Austin and Synthetic Biologics Inc. have developed two antibodies to potentially treat or prevent pertussis. After five years of development of the anti-pertussis therapeutic injections, preclinical testing on animals showed that the antibodies work as a prophylaxis to provide short-term immunity and as a treatment to accelerate recovery.
The findings from the preclinical studies were published in a paper in Science Translational Medicine. Dr. Jennifer Maynard, a chemical engineer in the Cockrell School of Engineering, is collaborating with Dr. Michael Kaleko, senior vice president of research and development for Synthetic Biologics, a co-author on the paper. Synthetic Biologics, a clinical-stage company focused on targeting pathogen-specific diseases, has licensed the antibodies from the University of Texas to eventually bring the product to market. The university is doing the bench work while the company is making gram-level quantities and designing clinical trials.
Kaleko calls it “a special relationship, in which the university brings scientific and clinical expertise and does the smaller studies, while the company does clinical and nonclinical development, analytics, toxicology and movement of the drugs into clinical trials.” Maynard calls the relationship “a great model for NIH grants, where we take things that start in a university and make them real.”
“Pertussis is a horrible disease that can be fatal in newborns, and antibiotics don’t stop it,” Kaleko explained. “The mechanistically simple antibodies we have developed have real potential to add to the standard of care in critically ill infants to diminish the complications and lower the mortality rate.”
Maynard added, “In the developing world, newborns are at a high risk of exposure. They can’t be vaccinated immediately when they are born. If we administer the antibody at birth, we can protect them from pertussis, preventing the infection from occurring in the first place.”
When an infant is infected with pertussis, a secreted toxin, called pertussis toxin, damages the immune system. The infant’s white blood cell count rises to dangerous levels in the bloodstream, and the cells could block blood flow through the lungs or cause the failure of other organs.
The antibodies block the function of the pertussis toxin, even after it binds to the blood cells, Maynard explained. The two antibodies, which potently neutralize pertussis toxin, can be used individually or be developed as a combination therapeutic. The first one binds to the toxin and prevents it from attaching to healthy cells, and the second stops the toxin from reaching its target within a healthy cell. When the antibodies neutralize pertussis toxin, they can bolster immune function and rapidly reduce the white blood cell count.
According to Kaleko, “There is evidence that more virulent strains make more pertussis toxins. We believe the key to preventing death is reducing the white blood cell load, which becomes extremely elevated during infection. If we can bring the count down or keep it low, the sick child may have a much better prognosis.”
When the antibodies were administered before infection in mice, the treatment acted as a vaccine, providing passive immunity to pertussis. When administered after infection in baboons, the antibodies lowered the white blood cell counts, accelerating recovery. While the antibodies did not completely eradiate the pertussis bacteria in animal models, they reduced the bacterial loads, moderated the symptoms and carried the newborns through the risk. The treatment could be combined with antibiotics to eliminate the bacteria that cause the illness.