Genetic stability of the live attenuated Bordetella pertussis vaccine candidate BPZE1

Area of Science:

• Microbiology
• Vaccinology
• Genetics

Background:

• Pertussis (whooping cough) remains a significant cause of childhood illness and death despite existing vaccines.
• Current pertussis vaccines have limitations in protecting very young infants.
• Natural Bordetella pertussis infection confers protection, suggesting a potential avenue for vaccine development.

Purpose of the Study:

• To develop a live attenuated Bordetella pertussis vaccine strain, BPZE1, for intranasal administration.
• To assess the genetic stability and protective capacity of the BPZE1 strain after extensive in vitro and in vivo passaging.

Main Methods:

• Genetic modification of Bordetella pertussis to create BPZE1 by inactivating pertussis toxin (ptx), deleting dermonecrotic toxin (dnt), and replacing the ampG gene.
• Continuous in vitro passaging (20 times) and in vivo passaging in mice (9 times).
• Analysis of passaged BPZE1 strains using PCR, DNA sequencing, DNA microarrays, and evaluation of protective efficacy in mice.

Main Results:

• BPZE1 was genetically modified to lack key virulence factors: pertussis toxin, dermonecrotic toxin, and tracheal cytotoxin.
• Extensive in vitro and in vivo passaging did not result in genetic alterations or loss of protective efficacy.
• Passaged BPZE1 strains maintained the genetic modifications and conferred protection comparable to the original strain.

Conclusions:

• The live attenuated Bordetella pertussis vaccine strain BPZE1 exhibits robust genetic stability.
• BPZE1 demonstrates consistent protective capacity after prolonged passaging, indicating its suitability as a vaccine candidate.
• The stability of BPZE1 addresses concerns for its development as an attenuated live vaccine against whooping cough.