Research Uncovers Antibodies to Improve Whooping Cough Vaccination

Whooping cough, also known as pertussis, was a significant cause of mortality among children in the United States and globally before the introduction of vaccines in the 1940s. Following the rollout of these vaccines, incidences of the disease plummeted, leading to a dramatic decrease in fatalities to single digits annually.

However, recent years have witnessed a resurgence of whooping cough, attributed primarily to declining vaccination rates exacerbated by the COVID-19 pandemic. In 2024, outbreaks led to a considerable influx of patients, particularly infants, who are too young to be vaccinated and are at heightened risk of severe symptoms.

In light of this alarming trend, a new study from The University of Texas at Austin presents promising developments aimed at enhancing whooping cough vaccines. The research targets two significant vulnerabilities in the infection, focusing on the pertussis toxin (PT), which is produced by the bacteria and plays a critical role in undermining the immune response and exacerbating symptoms.

The study, published in the Proceedings of the National Academy of Sciences, highlights two potent antibodies, hu11E6 and hu1B7, that neutralize the PT through different mechanisms. Employing advanced cryo-electron microscopy techniques, the researchers identified specific epitopes on the PT where these antibodies attach. Epitopes are areas that the immune system can recognize and target to combat pathogens. The hu11E6 antibody prevents the toxin from binding to human cells by disrupting sugar-binding sites, while hu1B7 blocks the toxin's entry into cells, thus mitigating its harmful effects. These findings are groundbreaking as they provide a detailed map of critical regions on the toxin, thereby laying the groundwork for future vaccine enhancements.

Jennifer Maynard, a professor in the Cockrell School of Engineering at UT, emphasized the potential for integrating these findings into forthcoming vaccine formulations. Current vaccine innovations include mRNA technology, similar to that used in COVID-19 vaccinations, and genetic engineering approaches that aim to produce safer, more effective recombinant acellular pertussis vaccines. By training the immune system to target the most vulnerable sites on the toxin, the research aims to create vaccines that not only provide stronger protection but also last longer, potentially increasing public willingness to receive vaccinations.

In addition to guiding future vaccine development, the antibodies hu1B7 and hu11E6 may also serve as therapeutic options for infants who are infected or at high risk. Previous studies suggest these antibodies can mitigate the lethal effects of pertussis infection, and researchers at UT are seeking partnerships to explore methods to prevent lung damage and fatalities in newborns exposed to the disease.

Whooping cough, caused by the bacterium Bordetella pertussis, is notorious for its severe coughing episodes, which can result in complications such as pneumonia, seizures, and, in extreme cases, death, particularly among infants. The disease is sometimes referred to as the '100-day cough' due to the prolonged nature of the coughing fits, which can persist for months even in less severe cases. Each year, approximately 200,000 individuals, predominantly infants and children, succumb to whooping cough worldwide, with survivors often facing long-term health consequences such as brain damage and lung scarring.

While modern vaccines have significantly reduced the incidence of whooping cough, their effectiveness diminishes over time, typically offering protection for only two to five years. The current acellular vaccines contain components of the bacteria that train the immune system to recognize the pathogen, including PT. Recent global outbreaks have caught public health officials off guard; for instance, New York City reported a staggering 169% increase in whooping cough cases since 2023, with a 500% rise since 2019. Australia is currently experiencing its largest whooping cough outbreak since the 1940s, with approximately 41,000 cases reported this year.

Experts attribute these outbreaks to missed initial vaccinations and booster shots. In addition to scientific advancements in combating whooping cough, there is a pressing need to address vaccine hesitancy. The most effective way to protect vulnerable newborns is through maternal vaccination during pregnancy, which provides immunity to infants until they are old enough to receive vaccinations themselves. While the full vaccination rate among kindergarteners in the U.S. usually exceeds 90%, only about 60% of expecting mothers receive the pertussis vaccine during pregnancy. The skepticism surrounding vaccine safety and the slow return to routine vaccination post-COVID-19 have contributed to under-vaccinated communities, creating an environment ripe for outbreaks.

In light of these challenges, the focus on neutralizing epitopes--regions where antibodies can effectively inhibit the toxin--could lead to the development of vaccines that offer stronger, more lasting immunity. This approach may help restore public trust in pertussis vaccines and mitigate the resurgence of the disease.