Genetic stability of the live attenuated Bordetella pertussis vaccine candidate BPZE1

Feunou, Pascal Feunou; Ismaïli, Jamila; Debrie, Anne-Sophie; Huot, Ludovic; Hot, David; Raze, Dominique; Lemoine, Yves; Locht, Camille

doi:10.1016/j.vaccine.2008.08.018

Cited by 30 publications

(21 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1, three hours (Day 0) and eight weeks (Day 60) after infection, B. pertussis BPSM organisms were present in the lungs of the SCID mice. Whereas all the bacteria were essentially cleared in the immuno-competent mice 8 weeks after challenge, the SCID mice contained roughly 10 fold more bacteria at 8 weeks after challenge compared to day 0, similar to what is usually seen in immuno-competent mice at day 7 post-infection [21], [22]. These results are consistent with the fact that adaptive immunity is required for the clearance of B. pertussis from the mouse respiratory tract [23], and allow us to use SCID mice as a suitable model to identify the effector mechanisms of adaptive immunity induced by BPZE1 against B. pertussis .…”

Section: Resultssupporting

confidence: 59%

“…The mice were i.n. immunized as previously described [21], [22]. Briefly, mice (groups of 4–5 mice) were slightly sedated with pentobarbital (CEVA Santé Animale - La Ballastière, France) and inoculated by pipetting 20 µl PBS containing approximately 1×10 6 CFU of B. pertussis BPZE1, B. pertussis BPSM or B. parapertussis onto the tip of the nares.…”

Section: Methodsmentioning

confidence: 99%

“…Athough BPZE1 does not produce tracheal cytotoxin and dermonecrotic toxin, it still produces immunogenic PTX, albeit in a genetically detoxified form. This vaccine strain is highly protective against B. pertussis challenge in mouse models and showed genetic stability during in vivo or in vitro passages [22]. Interestingly, BPZE1 also conferred significant cross-protection against B. parapertussis infection [21].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

T- and B-Cell-Mediated Protection Induced by Novel, Live Attenuated Pertussis Vaccine in Mice. Cross Protection against Parapertussis

2010

Self Cite

View full text Add to dashboard Cite

BackgroundDespite the extensive use of efficacious vaccines, pertussis still ranks among the major causes of childhood mortality worldwide. Two types of pertussis vaccines are currently available, whole-cell, and the more recent acellular vaccines. Because of reduced reactogenicity and comparable efficacy acellular vaccines progressively replace whole-cell vaccines. However, both types require repeated administrations for optimal efficacy. We have recently developed a live attenuated vaccine candidate, named BPZE1, able to protect infant mice after a single nasal administration.Methodology/Principal FindingsWe determined the protective mechanism of BPZE1-mediated immunity by using passive transfer of T cells and antibodies from BPZE1-immunized mice to SCID mice. Clearance of Bordetella pertussis from the lungs was mediated by both BPZE1-induced antibodies and CD4+, but not by CD8+ T cells. The protective CD4+ T cells comprised IFN-γ-producing and IL-17-producing subsets, indicating that BPZE1 induces both Th1 and Th17 CD4+ T cells. In addition, and in contrast to acellular pertussis vaccines, BPZE1 also cross-protected against Bordetella parapertussis infection, but in this case only the transfer of CD4+ T cells conferred protection. Serum from BPZE1-immunized mice was not able to kill B. parapertussis and did not protect SCID mice against B. parapertussis infection.Conclusions/SignificanceThe novel live attenuated pertussis vaccine BPZE1 protects in a pre-clinical mouse model against B. pertussis challenge by both BPZE1-induced antibodies and CD4+ T cell responses. It also protects against B. parapertussis infection. However, in this case protection is only T cell mediated.

show abstract

Section: Resultssupporting

confidence: 59%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

T- and B-Cell-Mediated Protection Induced by Novel, Live Attenuated Pertussis Vaccine in Mice. Cross Protection against Parapertussis

2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…3), which is boosted on encounter with virulent bacteria. Previous preclinical studies have shown that BPZE1 is genetically stable (13,31), safe in neonatal and immunocompromised mouse models (41), and a feasible vehicle for vaccination with heterologous antigens (18). This study demonstrates that live, attenuated BPZE1 confers protection against virulent B. pertussis challenge, consisting of a Th1 memory response, high-titer B. pertussis-specific serum antibody, and the priming of a pertussisspecific memory B-cell response that persists 1 year following vaccination.…”

Section: Discussionmentioning

confidence: 54%

A Live, AttenuatedBordetella pertussisVaccine Provides Long-Term Protection against Virulent Challenge in a Murine Model

Skerry

Mahon

2011

Clin Vaccine Immunol

View full text Add to dashboard Cite

“…In pre-clinical models, BPZE1 was shown to be safe, including in severely immuno-compromised animals [13], and able to induce fast, strong and long-lasting protective immunity after a single nasal administration, even in newborn animals [14], [15]. The excellent safety profile of BPZE1 and its demonstrated genetic stability [16] have allowed this strain to be declassified from the safety level 2 to level 1 in several countries, a pre-requisite for its clinical development.…”

Section: Introductionmentioning

confidence: 99%

A Phase I Clinical Study of a Live Attenuated Bordetella pertussis Vaccine - BPZE1; A Single Centre, Double-Blind, Placebo-Controlled, Dose-Escalating Study of BPZE1 Given Intranasally to Healthy Adult Male Volunteers

et al. 2014

Self Cite

View full text Add to dashboard Cite

BackgroundAcellular pertussis vaccines do not control pertussis. A new approach to offer protection to infants is necessary. BPZE1, a genetically modified Bordetella pertussis strain, was developed as a live attenuated nasal pertussis vaccine by genetically eliminating or detoxifying 3 toxins.MethodsWe performed a double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally for the first time to human volunteers, the first trial of a live attenuated bacterial vaccine specifically designed for the respiratory tract. 12 subjects per dose group received 103, 105 or 107 colony-forming units as droplets with half of the dose in each nostril. 12 controls received the diluent. Local and systemic safety and immune responses were assessed during 6 months, and nasopharyngeal colonization with BPZE1 was determined with repeated cultures during the first 4 weeks after vaccination.ResultsColonization was seen in one subject in the low dose, one in the medium dose and five in the high dose group. Significant increases in immune responses against pertussis antigens were seen in all colonized subjects. There was one serious adverse event not related to the vaccine. Other adverse events were trivial and occurred with similar frequency in the placebo and vaccine groups.ConclusionsBPZE1 is safe in healthy adults and able to transiently colonize the nasopharynx. It induces immune responses in all colonized individuals. BPZE1 can thus undergo further clinical development, including dose optimization and trials in younger age groups.Trial RegistrationClinicalTrials.gov NCT01188512

show abstract

Genetic stability of the live attenuated Bordetella pertussis vaccine candidate BPZE1

Cited by 30 publications

References 16 publications

T- and B-Cell-Mediated Protection Induced by Novel, Live Attenuated Pertussis Vaccine in Mice. Cross Protection against Parapertussis

T- and B-Cell-Mediated Protection Induced by Novel, Live Attenuated Pertussis Vaccine in Mice. Cross Protection against Parapertussis

A Live, AttenuatedBordetella pertussisVaccine Provides Long-Term Protection against Virulent Challenge in a Murine Model

A Phase I Clinical Study of a Live Attenuated Bordetella pertussis Vaccine - BPZE1; A Single Centre, Double-Blind, Placebo-Controlled, Dose-Escalating Study of BPZE1 Given Intranasally to Healthy Adult Male Volunteers

Contact Info

Product

Resources

About