Live Attenuated Pertussis Vaccine BPZE1 Protects Baboons Against Bordetella pertussis Disease and Infection

Locht, Camille; Papin, James F.; Lecher, Sophie; Debrie, Anne-Sophie; Thalen, Marcel; Solovay, Ken; Rubin, Keith; Mielcarek, Nathalie

doi:10.1093/infdis/jix254

Cited by 70 publications

(62 citation statements)

References 21 publications

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“…28 The reasons for these conflicting findings are not known, but may potentially be due to the fact that we used the genetically attenuated BPZE1 strain, whereas in the previous study, virulent B. pertussis was used for the initial infection. However, our findings are consistent with our previous study showing BPZE1-induced protection against nasal infection in baboons, 16 in contrast to aPV. 12 In the mice, the nasal anti-B.…”

Section: Discussionsupporting

confidence: 94%

“…14 ) It is now in clinical development and was shown to be safe in humans, able to transiently colonize the human respiratory tract and to induce immune responses in all colonized individuals. 15 It has recently been tested in baboons, where it induced strong protection against pertussis disease after a single vaccination and reduced nasopharyngeal B. pertussis colonization by 99.998% over non-vaccinated baboons, 16 a performance that by far exceeded that of three administrations of a human dose of aPV and wholecell vaccine. 12 However, the mechanism responsible for the protection against nasal colonization has not been addressed yet.…”

Section: Introductionmentioning

confidence: 99%

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IL-17-dependent SIgA-mediated protection against nasal Bordetella pertussis infection by live attenuated BPZE1 vaccine

et al. 2018

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BPZE1 is a live attenuated Bordetella pertussis vaccine for nasal administration to mimic the natural route of infection. Here, we studied the mechanism of BPZE1-induced immunity in the murine nasal cavity in contrast to acellular vaccine (aPV), although both vaccines protected against lung colonization. Transfer of splenocytes or serum from BPZE1-vaccinated or aPV-vaccinated mice protected naïve mice against lung colonization but not against nasal colonization. However, transfer of nasal washes from BPZE1-vaccinated mice resulted in protection against nasal colonization, which was lost in IgA-deficient or poly-Ig receptor-deficient mice, indicating that it depends on secretory IgA (SIgA) induction induced in the nose. BPZE1-induced protection against nasal colonization was long-lived despite the relatively rapid decay of SIgA, indicating a potent BPZE1-induced local memory response, likely due to CD4 tissue-resident memory T cells induced in the nose by BPZE1. These cells produced interleukin-17 (IL-17), known to be important for SIgA secretion. Furthermore, BPZE1 failed to protect Il17 mice against nasal colonization by B. pertussis and induced only background levels of nasal SIgA. Thus, our results show important differences in the protective mechanism between the upper and the lower murine respiratory tract and demonstrate an IL-17-dependent SIgA-mediated mechanism of BPZE1-induced protection against B. pertussis nasopharyngeal colonization.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

IL-17-dependent SIgA-mediated protection against nasal Bordetella pertussis infection by live attenuated BPZE1 vaccine

et al. 2018

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“…Hence, use of currently marketed vaccines against tuberculosis (BCG), measles, mumps and rubella, varicella-zoster, rotavirus, influenza (nasal) and yellow fever is universally discouraged. Newer more effective vaccines under development, e.g., new pertussis vaccine BPZE1 (44), also may not become available to the immunocompromised. Replication-competent controlled virus vectors expressing antigens of the latter microbes in the context of efficient viral replication can be expected to elicit similarly or more potent immune reactions as the contraindicated live attenuated vaccines.…”

Section: Discussionmentioning

confidence: 99%

Immunization by replication-competent controlled herpesvirus vectors

Bloom¹,

Tran²,

Feller³

et al. 2018

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Replication-competent controlled virus vectors were derived from virulent HSV-1 2 wildtype strain 17syn+ by placing one or two replication-essential genes under the 3 stringent control of a gene switch that is co-activated by heat and an antiprogestin. 4Upon activation of the gene switch, the vectors replicate in infected cells with an efficacy 5 that approaches that of the wildtype virus from which they were derived. Essentially no 23. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/299230 doi: bioRxiv preprint first posted online Apr. 11, 2018; 3 IMPORTANCE 1 We hypothesized that vigorous replication of a pathogen may be critical for eliciting the

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“…In this sense, alternative pertussis vaccines have been suggested, including a live attenuated pertussis vaccine [25] and a whole cell pertussis vaccine with reduced content of endotoxin [26]. Although with efficient and safe alternatives for prevention, pertussis is still the most frequent and lethal immunopreventable disease.…”

Section: Introductionmentioning

confidence: 99%