Texas engineers develop potential treatment for whooping cough

December 02, 2015

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, the highly contagious respiratory tract infection that affects millions of infants around the world and results in an estimated 200,000 child deaths every year.

For the past five years, the research team has worked to develop two antibodies as a new anti-pertussis therapeutic injection. The team's efforts recently paid off as preclinical testing conducted on animals demonstrated that their 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 on Dec. 2 in Science Translational Medicine.

Commonly known as whooping cough, the disease causes painful fits of coughing and life-threatening symptoms in infants and has had a devastating impact worldwide. According to the Centers for Disease Control and Prevention, more than 16 million pertussis cases occur annually, and the disease continues to be a major cause of infant death in developing nations. In the United States, childhood vaccinations largely prevent the disease, but there still has been an increase in incidence during the past 20 years, including several outbreaks in recent years. Antibiotics are frequently ineffective in severe pertussis, and there is no specific therapeutic to treat pertussis in these infants or prevent it in vulnerable infants too young to be vaccinated -- but now there may be hope for the future.

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 UT Austin to eventually bring the product to market.

"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," Maynard said. "If we can get our antibodies to these high-risk infants, we could potentially prevent 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 and causes the infant's white blood cell count to rise to dangerous levels in the bloodstream -- levels where the cells could block blood flow through the lungs.

Maynard's two antibodies potently neutralize pertussis toxin and could be used individually or be developed as a combination therapeutic. The first binds to the toxin and prevents it from attaching to healthy cells; the second stops the toxin from reaching its target within a healthy cell.

By neutralizing pertussis toxin, the antibodies are anticipated to bolster immune function and rapidly reduce the white blood cell count.

"We believe the key to preventing death is reducing the white blood cell load, which becomes extremely elevated during infection," Kaleko said. "If we can bring the count down or keep it low, the sick child may have a much better prognosis."

When the team administered the antibodies before infection in mice, the treatment acted as a vaccine, giving passive immunity to pertussis. When administered after infection in nonhuman primates, the antibodies lowered the white blood cell counts, speeding recovery.

In animal models, the antibodies did not completely eradicate the pertussis bacteria, but they diminished the bacterial loads and kept symptoms at bay. The researchers think the treatment could be combined with antibiotics to eliminate the bacteria that cause the illness.

The team's long-term plans are to advance an antibody product to human trials to evaluate its potential for two clinical applications. As a treatment, the therapeutic may be tested in critically ill infants with pertussis to potentially shorten the disease's course, mitigate complications and diminish mortality. As a prophylactic, the therapeutic has the potential to provide antibody protection instantly to at-risk newborns in the developing world to protect them from pertussis for the first few months of life, the timeframe during which the infants are at greatest risk for severe disease but are too young to be immunized.

"We want to make sure that our research is really going to have impact," Maynard said. "Most of the babies who get sick haven't been immunized, so we hope to provide the immunity that they are lacking."
The University of Texas at Austin is committed to transparency and disclosure of all potential conflicts of interest. The university investigator who led this research, Jennifer Maynard, has submitted required financial disclosure forms with the university. Maynard has received research funding for this project from Synthetic Biologics, a clinical-stage company that is a key collaborator and co-author, as well as the Welch Foundation and the Norman Hackerman Advanced Research Project. She has received funding for past projects from other corporate sponsors, including Cephalon and Pfizer, and from major national science funding agencies, including the National Institutes of Health, the Department of Defense and the National Science Foundation.

University of Texas at Austin

Related Antibodies Articles from Brightsurf:

Scientist develops new way to test for COVID-19 antibodies
New research details how a cell-free test rapidly detects COVID-19 neutralizing antibodies and could aid in vaccine testing and drug discovery efforts.

Mussels connect antibodies to treat cancer
POSTECH research team develops innovative local anticancer immunotherapy technology using mussel protein.

For an effective COVID vaccine, look beyond antibodies to T-cells
Most vaccine developers are aiming solely for a robust antibody response against the SARS-CoV-2 virus, despite evidence that antibodies are not the body's primary protective response to infection by coronaviruses, says Marc Hellerstein of UC Berkeley.

Children can have COVID-19 antibodies and virus in their system simultaneously
With many questions remaining around how children spread COVID-19, Children's National Hospital researchers set out to improve the understanding of how long it takes pediatric patients with the virus to clear it from their systems, and at what point they start to make antibodies that work against the coronavirus.

The behavior of therapeutic antibodies in immunotherapy
Since the late 1990s, immunotherapy has been the frontline treatment against lymphomas where synthetic antibodies are used to stop the proliferation of cancerous white blood cells.

Re-engineering antibodies for COVID-19
Catholic University of America researcher uses 'in silico' analysis to fast-track passive immunity

Seroprevalence of antibodies to SARS-CoV-2 in 10 US sites
This study estimates how common SARS-CoV-2 antibodies are in convenience samples from 10 geographic sites in the United States.

Neutralizing antibodies in the battle against COVID-19
An important line of defense against SARS-CoV-2 is the formation of neutralizing antibodies.

Three new studies identify neutralizing antibodies against SARS-CoV-2
A trio of papers describes several newly discovered human antibodies that target the SARS-CoV-2 virus, isolated from survivors of SARS-CoV-2 and SARS-CoV infection.

More effective human antibodies possible with chicken cells
Antibodies for potential use as medicines can be made rapidly in chicken cells grown in laboratories.

Read More: Antibodies News and Antibodies Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.