| Summary: | Whooping cough, or pertussis, mostly caused by <i>Bordetella pertussis</i>, is a respiratory disease that affects all age groups, but severe and fatal pertussis occurs almost exclusively in young children. The widespread use of whole-cell and, more recently, of acellular vaccines has substantially reduced the disease incidence. However, it has not been eliminated in any part of the world and has made a worrisome rebound in several areas. Cocoon and maternal immunization have been implemented in several countries but have their intrinsic limitations. To effectively control pertussis, novel vaccines are needed that protect against disease and prevent <i>B. pertussis</i> infection and transmission, which is not the case for current vaccines. Several approaches are contemplated, including alternative administration routes, such as nasal immunization, improvement of acellular vaccines by adding more antigens and T-cell-promoting adjuvants, and the development of novel vaccines, such as outer membrane vesicles and live attenuated vaccines. Among them, only a live attenuated vaccine has so far been assessed for safety and immunogenicity in preclinical models other than mice and is in clinical development. Before any of these vaccines can be used in neonates, extensive safety and immunogenicity assessment in pre-clinical neonatal models and in carefully designed clinical trials is necessary. The aim of this review is to discuss the current pertussis problem, implemented strategies to resolve it, the value of animal models and novel vaccine approaches.
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