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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Live pertussis vaccines: will they protect against carriage and spread of pertussis?
1University of Lille, U1019-UMR 8204, Centre for Infection and Immunity of Lille, Lille, France; CNRS, UMR 8204, F-59000 Lille, France; Inserm, U1019, F-59000 Lille, France; CHU Lille, F-59000 Lille, France; Institut Pasteur de Lille, F-59000 Lille, France.
Insights
Pertussis remains a global threat despite widespread vaccination. New nasal vaccines, like the attenuated Bordetella pertussis strain BPZE1, show promise in preventing infection and transmission, potentially controlling the disease.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Pertussis, caused by Bordetella pertussis, is a severe respiratory illness particularly dangerous for infants.
- Despite high vaccination rates, pertussis has resurged globally, even in industrialized nations.
- Current acellular vaccines may have waning immunity and do not prevent asymptomatic transmission.
Purpose of the Study:
- To explore reasons for the resurgence of pertussis.
- To evaluate novel vaccine strategies for controlling pertussis.
- To assess the safety and immunogenicity of the BPZE1 vaccine candidate.
Main Methods:
- Review of pertussis epidemiology and vaccine effectiveness.
- Analysis of mathematical modeling studies on pertussis transmission.
- Evaluation of non-human primate studies on vaccine efficacy.
- Assessment of Phase I clinical trial data for the BPZE1 vaccine.
Main Results:
- Asymptomatic transmission of Bordetella pertussis is a key driver of the pertussis resurgence.
- Neither whole-cell nor acellular vaccines prevent infection and transmission in non-human primates.
- The genetically attenuated Bordetella pertussis strain BPZE1 was safe in a Phase I trial.
- BPZE1 transiently colonized the nasopharynx and induced antibody responses in human volunteers.
Conclusions:
- New vaccine approaches, such as nasal administration mimicking natural infection, are needed for effective pertussis control.
- The BPZE1 vaccine candidate demonstrates safety and immunogenicity, warranting further efficacy trials.
- Future research should focus on human efficacy trials to determine BPZE1's potential in controlling pertussis.
Abstract:
Pertussis is a severe respiratory disease that can be fatal in young infants. Its main aetiological agent is the Gram-negative micro-organism Bordetella pertussis. Vaccines against the disease have been in use since the 1950s, and global vaccination coverage has now reached more than 85%. Nevertheless, the disease has not been controlled in any country, and has even made a spectacular come-back in the industrialized world, where the first-generation whole-cell vaccines have been replaced by the more recent, less reactogenic, acellular vaccines. Several hypotheses have been proposed to explain these observations, including the fast waning of acellular vaccine-induced protection. However, recent mathematical modelling studies have indicated that asymptomatic transmission of B. pertussis may be the main reason for the current resurgence of pertussis. Recent studies in non-human primates have shown that neither whole-cell, nor acellular vaccines prevent infection and transmission of B. pertussis, in contrast to prior exposure. New vaccines that can be applied nasally to mimic natural infection without causing disease may therefore be useful for long-term control of pertussis. Several vaccine candidates have been proposed, the most advanced of which is the genetically attenuated B. pertussis strain BPZE1. This vaccine candidate has successfully completed a first-in-man phase I trial and was shown to be safe in young male volunteers, able to transiently colonize the nasopharynx and to induce antibody responses to B. pertussis antigens in all colonized individuals. Whether BPZE1 will indeed be useful to ultimately control pertussis obviously needs to be assessed by carefully conducted human efficacy trials.
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