An Old Foe Returns: Understanding the Resurgence of Whooping Cough and What’s Next for Vaccines
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Why is whooping cough, a disease we thought was largely under control, suddenly reappearing in outbreaks? Despite widespread vaccination efforts, pertussis—commonly known as whooping cough—has been resurging globally, raising questions about vaccine effectiveness and immunity. What is happening beneath the surface of our immune defenses, and how can science respond to this persistent threat?
TL;DR
- Current acellular pertussis vaccines protect against severe disease but do not fully prevent infection or transmission, contributing to whooping cough’s resurgence.
- New vaccine approaches—including novel adjuvants, additional antigens, live attenuated vaccines, and improved whole-cell formulations—are being developed to provide stronger, longer-lasting protection.
Whooping cough is caused by the bacterium Bordetella pertussis and is particularly dangerous for infants and those not fully immunized. Although vaccines have dramatically reduced pertussis cases since their introduction in the mid-20th century, outbreaks still occur every few years, resembling patterns from before vaccines were available. Notably, infants under one year of age suffer the highest rates of severe illness and hospitalization. The shift from whole-cell vaccines to acellular vaccines in the 1990s—driven by concerns about side effects—has been linked to changes in immunity and disease patterns, even though vaccine coverage remains high.
Researchers have studied pertussis immunity using a combination of epidemiological data, animal models (including baboons and mice), and clinical trials. These approaches have helped dissect how different vaccine formulations stimulate the immune system, particularly the types of T-cell responses they induce. Novel vaccine candidates have been tested for safety and efficacy in preclinical models and early human trials, with some progressing to advanced clinical testing. Additionally, molecular studies have identified new bacterial components that could serve as targets for improved vaccines.
The acellular pertussis (aP) vaccines currently in use generate a predominantly Th2-type immune response, which is effective at preventing severe disease but less so at stopping bacterial colonization in the nose and transmission to others. In contrast, whole-cell pertussis (wP) vaccines and natural infection induce a Th1/Th17 response that better clears bacteria from mucosal surfaces. This difference likely contributes to the resurgence of pertussis despite vaccination. Novel adjuvants that shift immune responses toward Th1/Th17, such as LP-GMP and T-Vant, show promise in animal studies. Live attenuated vaccines like BPZE1, delivered intranasally, have demonstrated safety and the ability to induce both mucosal and systemic immunity. Additionally, new antigens beyond those in current vaccines are being explored to broaden protection. Modified whole-cell vaccines with reduced side effects are also under development to combine the robust immunity of wP vaccines with improved tolerability.
Understanding the immunological nuances behind pertussis vaccine performance is critical for designing next-generation vaccines that not only prevent disease but also reduce infection and transmission. Improved vaccines could help curb the cyclical outbreaks of whooping cough and protect vulnerable populations, especially infants. The development of novel adjuvants, inclusion of additional bacterial antigens, and alternative vaccine platforms like live attenuated and refined whole-cell vaccines represent important steps toward more durable and comprehensive pertussis control.
While promising, many of the new vaccine candidates and adjuvants are still in preclinical or early clinical stages, and their long-term safety and effectiveness in diverse populations remain to be established. The complex interplay of immune memory, bacterial evolution, and vaccine-induced immunity means that pertussis control will require ongoing surveillance and possibly tailored vaccination strategies. Moreover, real-world factors such as vaccine acceptance and access continue to influence pertussis epidemiology.