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Abstract
The intensive use of pertussis vaccines has dramatically reduced the incidence of whooping cough during the 20th century. However, recent outbreaks in countries with high vaccination coverage illustrate the shortcomings of current vaccination regimens, and immunity induced by the most recent, acellular vaccines wanes much faster than anticipated. As an alternative, live attenuated vaccine candidates have recently been developed in order to mimic natural infection, which induces long-lasting immunity. One of them has successfully completed a Phase I trial in humans and is now undergoing further product and clinical developments. This article describes the development of such vaccines, discusses their advantages over existing vaccines and their interesting bystander properties as powerful anti-inflammatory agents, which widens their potential use far beyond that for protection against whooping cough.
Financial & competing interests disclosure
The authors declare that their institutions hold a patent folio on the live attenuated BPZE1 vaccine candidate, and that they are listed as co-inventors of these patents. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Key issues
The incidence of pertussis or whooping cough is rising in many countries with wide vaccination coverage.
Several strategies using the currently available vaccines have been proposed, but have failed to control the disease.
Acellular pertussis vaccine-acquired immunity wanes quickly in humans and fails to protect against infection in non-human primate models, in contrast to prior infection with B. pertussis.
Live attenuated nasal vaccines have a number of advantages over current vaccines, they mimic natural infection and are thus expected to induce long-lived immunity.
A live attenuated vaccine induces rapid and long-lasting immunity against B. pertussis challenge infection in preclinical models and has recently successfully completed a first-in-man clinical trial as a liquid formulation, which lacks stability.
Next product and clinical development steps include stabilization of the product, further safety, immunogenicity and efficacy trials.
The target population of live attenuated pertussis vaccines may first be adults and adolescents, and ultimately newborns, after careful stepwise evaluation to reach this ultimate target population.
