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AUSTIN, TX – As whooping cough makes a worrying comeback globally, new research from The University of Texas at Austin offers a significant step towards developing more effective vaccines by identifying key antibodies that neutralize the disease’s primary toxin.
Whooping cough, or pertussis, caused by the bacterium Bordetella pertussis, was largely controlled in the U.S. following the introduction of vaccines in the 1940s. However, recent years have seen a resurgence, exacerbated by declining vaccination coverage after the COVID-19 pandemic. This has led to significant outbreaks in 2024, overwhelming health systems and primarily endangering infants who are too young to be vaccinated and suffer the most severe consequences, including violent coughing fits, pneumonia, seizures, and potentially death or long-term damage. Globally, the disease claims an estimated 200,000 lives annually, mostly infants and children.
The new study, published in the Proceedings of the National Academy of Sciences, focuses on neutralizing pertussis toxin (PT), a potent substance produced by the bacteria that cripples the host’s immune response and causes many of the disease’s severe symptoms. Researchers from UT’s McKetta Department of Chemical Engineering and Department of Molecular Biosciences identified two powerful antibodies, hu11E6 and hu1B7, that effectively combat PT through different mechanisms.
Using advanced cryo-electron microscopy, the team precisely mapped the specific sites, or epitopes, on the PT molecule where these antibodies bind. Hu11E6 works by blocking the toxin from attaching to human cells, while hu1B7 prevents the toxin from entering cells and causing internal damage. This detailed mapping provides a crucial blueprint for designing improved vaccines.
“There are currently several promising new pertussis vaccines in the research and clinical trial phases,” stated Jennifer Maynard, professor of chemical engineering at the Cockrell School of Engineering and corresponding author of the study. “Our findings could be incorporated into future versions quite easily, improving overall effectiveness and longevity of protection.”
Maynard suggests that innovations like mRNA technology and genetically engineered pertussis toxin (PTgen) could integrate these findings to create safer, more potent vaccines. “Training the immune system to target the most vulnerable sites on the toxin is expected to create more effective vaccines,” she added. “And the more effective and longer-lasting a vaccine is, hopefully, the more people will take it.”
Current acellular vaccines, while helpful, offer protection that wanes over time, typically lasting only two to five years. The recent surge in cases underscores the need for improvement. New York City reported a 169% increase in cases since 2023 this past fall, and Australia is experiencing its largest outbreak since the 1940s, with potentially over 41,000 cases this year. Health officials attribute these outbreaks largely to missed initial and booster vaccinations.
Beyond vaccine development, the identified antibodies, hu1B7 and hu11E6, also hold promise as therapeutic agents, particularly for infants already infected or at high risk. Previous research by Maynard and colleagues demonstrated their potential to prevent the lethal effects of pertussis. UT researchers are now actively seeking partnerships to develop these antibody-based therapies.
Despite the scientific progress, researchers acknowledge the challenge posed by vaccine hesitancy. While overall childhood vaccination rates remain relatively high in the US (typically over 90% for kindergarteners), vaccination during pregnancy – the most effective way to protect newborns – lags significantly, with under 60% of mothers receiving the booster. This gap leaves newborns vulnerable.
“It’s always easier to prevent disease in a high-risk person,” emphasized Annalee W. Nguyen, a research professor in chemical engineering and study co-author. “Mothers have an incredible opportunity to shield their babies after they are born by getting a pertussis booster vaccination during pregnancy.”
By developing vaccines that target these newly identified neutralizing epitopes, scientists hope to provide stronger, longer-lasting immunity, which could, in turn, help bolster public confidence and curb the resurgence of this dangerous disease.
Disclaimer: This news article is based on information provided from a study published in the Proceedings of the National Academy of Sciences and related press materials from The University of Texas at Austin. It is intended for informational purposes only and does not constitute medical advice. Consult with healthcare professionals for any health concerns or vaccination decisions.(Jory A. Goldsmith et al, Structural basis for neutralizing antibody binding to pertussis toxin, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2419457122)
