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Antibodies Reduce Whooping Cough Severity, Infections

Jennifer Maynard

Jennifer Maynard (University of Texas in Austin)

3 December 2015. Two engineered antibodies were shown in tests with lab animals to reduce the severity of whooping cough symptoms and white blood cell counts indicating infection. The team from the protein engineering lab of Jennifer Maynard at University of Texas in Austin and Synthetic Biologics, a biotechnology company in Rockville, Maryland, published its findings yesterday in the journal Science Translational Medicine (paid subscription required).

Whooping cough, also known as pertussis, is a highly contagious bacterial infection of the respiratory tract that affects primarily children, and results in a severe hacking cough, followed by high-pitched breathing that sounds like a “whoop.” The number of pertussis cases is growing in the U.S. due to parents delaying or avoiding vaccinations for their children, and particularly in low-resource countries where many families do not have access to vaccines. Centers for Disease Control and Prevention estimates 16 million cases of pertussis occur each year, resulting in some 195,000 deaths worldwide.

Maynard and colleagues conducted earlier research leading to the discovery of the antibodies, hu1B7 and hu11E6. Unlike antibiotics that target the bacteria causing the infection, these antibodies aim to neutralize the toxins caused by the infection that result in the severe coughing symptoms. The first antibody binds to the pertussis toxin, preventing it from attaching to healthy cells, while the second antibody blocks the toxin from reaching its target inside healthy cells.

By neutralizing pertussis toxins, the antibodies are expected to boost immune systems of recipients — mainly infants — and reduce their white blood cell counts. Synthetic Biologics licensed Maynard’s technology and is developing a treatment for pertussis, code-named SYN-005, based on the two antibodies.

The study evaluated the antibody combination in young lab animals, first mice, then baboons. The experiments with mice tested the antibodies as a vaccine, where the researchers found the antibodies stopped inhaled airborne bacteria from infecting the recipients, preventing a rise in white blood cell counts.

In the baboon tests, the young animals were induced with pertussis bacteria, then treated with the antibodies after the bacteria colonized in their respiratory tracts. Before treatment, the baboons experienced higher white blood counts and heavy coughing in 3 to 4 days. After treatment, results show white blood cell counts stopped rising, heavy coughing bouts were reduced, and pertussis bacteria were cleared faster in recipients of the antibodies, compared to untreated animals.

Maynard and Synthetic Biologics are developing the antibodies for clinical trials along two tracks. As a preventive vaccine, the antibodies can be given to infants in their first few months of life to protect against pertussis during this vulnerable period. As reported in Science & Enterprise, the Bill and Melinda Gates Foundation is funding an evaluation by Maynard’s lab of the hu1B7 antibody as a vaccine for newborns, particularly in low-resource regions.

“In the developing world, an estimated 200,000 babies die a year, and that’s where we think we can have a really big impact,” says Maynard in a university statement. “If we can get our antibodies to these high-risk infants, we could potentially prevent the infection from occurring in the first place.”

As a treatment for pertussis, the antibodies could be given to infants infected with pertussis bacteria to mitigate the effects of the toxins and reduce severity of the symptoms. While the antibodies in the study succeeded in neutralizing the toxins, they still did not eliminate the bacteria, thus the antibodies as a treatment may need to be combined with antibiotics.

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