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Genetic stability of the live attenuated Bordetella pertussis vaccine candidate BPZE1.

Abstract：

:Despite the extensive use of efficacious pertussis vaccines, Bordetella pertussis infections are still among the main causes for childhood morbidity and mortality. Severe pertussis occurs mostly in very young children, often too young to be sufficiently protected by current vaccines, which require several administrations in regimens that vary between countries. Since natural infection with B. pertussis is able to induce protection, we have developed the live attenuated B. pertussis vaccine strain BPZE1 that protects mice upon a single intranasal administration. This strain was obtained by genetically inactivating pertussis toxin via two point mutations in the ptx gene, by deleting dnt encoding dermonecrotic toxin, and by replacing the B. pertussis ampG gene by Escherichia coli ampG, resulting in the removal of tracheal cytotoxin. Here, we assessed the genetic stability of BPZE1 after 20 and 27 weeks of continuous passaging in vitro and in vivo, respectively. BPZE1 was passaged 20 times in vitro and 9 times in vivo in Balb/C mice. After these passages, 8 hemolytic colonies were analyzed by PCR for the absence of dnt and B. pertussis ampG and the presence of E. coli ampG, by DNA sequencing for the presence of the two ptx point mutations and by DNA microarrays for the global genomic stability. In addition, the protective capacity of BPZE1 was evaluated after the passages. No genetic or protective difference was detected between the passaged bacteria and non-passaged BPZE1, indicating that stability of the vaccine strain is not a concern for BPZE1 to be considered as an attenuated live vaccine against whooping cough.

journal_name

Vaccine

journal_title

Vaccine

authors

Feunou PF,Ismaili J,Debrie AS,Huot L,Hot D,Raze D,Lemoine Y,Locht C

doi

10.1016/j.vaccine.2008.08.018

subject

Has Abstract

pub_date

2008-10-23 00:00:00

pages

5722-7

issue

45

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(08)01112-2

journal_volume

26

pub_type

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