Whooping cough. Credit: The University of Texas at Austin.
Whooping cough, or pertussis, was once a leading cause of death for children before the introduction of vaccines in the 1940s.
In the decades since, the bacterial disease was nearly eradicated in the US, with fatalities falling to double digits each year.
But the disease has made a troubling comeback in recent years as vaccine coverage declined after the COVID-19 pandemic.
In 2024, several outbreaks left public health officials and hospitals scrambling to accommodate a sudden influx of patients, primarily infants, who are often too young to be vaccinated and suffer the most severe symptoms.
Now, new research from The University of Texas at Austin could aid in improving whooping cough vaccines to once again push this disease toward eradication by targeting two key weaknesses in the infection.
A new target
Against this backdrop, a team of researchers, including members of UT’s McKetta Department of Chemical Engineering and Department of Molecular Biosciences, has made significant strides in understanding and enhancing pertussis immunity.
One of the things that makes pertussis infections dangerous is pertussis toxin (PT), a chemical weapon produced by the bacteria that weakens a patient’s immune response and causes many of the severe symptoms associated with whooping cough.
The new research focuses on two powerful antibodies, hu11E6 and hu1B7, which neutralise the PT in different ways.
Using cutting-edge cryo-electron microscopy approaches, the researchers identified the specific epitopes on PT where these antibodies bind.
Epitopes are chemical targets the immune system can zero in on to fight pathogens. Hu11E6 blocks the toxin from attaching to human cells by interfering with sugar-binding sites, while hu1B7 prevents the toxin from entering cells and causing harm.
These findings are the first to precisely map these critical regions, providing a blueprint to improve vaccines.
Corresponding author Jennifer Maynard, professor of chemical engineering at the Cockrell School of Engineering, said: “There are currently several promising new pertussis vaccines in the research and clinical trial phases.
“Our findings could be incorporated into future versions quite easily, improving overall effectiveness and longevity of protection.”
Innovations
She pointed to innovations like mRNA technology used in the COVID-19 vaccine, as well as breakthroughs in using genetic engineering on pertussis toxin (PTgen) to generate safer and more potent new recombinant acellular pertussis vaccines as technologies preserving neutralising epitopes that can combine with her team’s new findings.
Maynard said: “Training the immune system to target the most vulnerable sites on the toxin is expected to create more effective vaccines.
“And the more effective and longer-lasting a vaccine is, hopefully, the more people will take it.”
In addition to helping guide future vaccine designs, the hu1B7 and hu11E6 antibodies themselves hold promise as therapeutic medicines for infected and high-risk infants.
Previous work by Maynard and colleagues showed that they can prevent the lethal aspects of pertussis infection.
Dual challenge
While advances in fighting pertussis are exciting, they face a dual challenge: overcoming the biological complexity of pertussis and the societal hurdles of vaccine hesitancy.
The most effective way to prevent pertussis in vulnerable newborns is for mothers to be vaccinated during pregnancy, which confers protection to the newborn until it is old enough to be vaccinated.
The full vaccination rate against pertussis in kindergarteners is typically over 90% in the US, but under 60% of mothers receive the vaccine during pregnancy.
Scepticism about vaccine safety and slow normalisation of routine vaccination after the COVID-19 pandemic has led to pockets of under-vaccinated communities and overall low protection of newborns, providing fertile ground for deadly outbreaks.
This environment, coupled with the limitations of current vaccines, makes innovation essential.
Co-author Annalee W Nguyen, a research professor in chemical engineering, emphasised the importance of prevention over treatment: “It’s always easier to prevent disease in a high-risk person.
“Once someone is extremely ill, their immune system isn’t functioning well, and it’s harder to help them recover.
“Mothers have an incredible opportunity to shield their babies after they are born by getting a pertussis booster vaccination during pregnancy, and parents can continue to protect their families by working with their paediatrician to ensure children and teens are up-to-date on vaccinations.”
By focusing on neutralising epitopes – areas where antibodies can effectively block the toxin – new vaccines can potentially provide stronger, longer-lasting immunity.
This could help bolster public confidence in pertussis vaccines and curb the disease’s resurgence.
The study is published in the Proceedings of the National Academy of Sciences.
