{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:28:26Z","timestamp":1790947706309,"version":"4.1.0"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pertussis is a severe respiratory disease mainly caused by Bordetella pertussis. Despite wide global vaccination coverage with efficacious pertussis vaccines, it remains one of the least well-controlled vaccine-preventable diseases, illustrating the shortcomings of the current vaccines. We have developed the live attenuated nasal pertussis vaccine BPZE1, currently undergoing clinical evaluation in human phase 2 trials. We have previously shown that in mice, BPZE1 provides strong and long-lasting protection against B. pertussis challenge by inducing potent Ab and T cell responses as well as secretory IgA and IL-17\u2013producing resident memory T lymphocytes in the nasal cavity. In this study, we show that BPZE1 induces protection in mice against B. pertussis within days after vaccination, at a time when Ab and T cell responses were not detectable. Early protection was independent of T and B cell responses, as demonstrated by the use of SCID mice. Instead, it was due to TLR4-dependent signaling through the MyD88-dependent pathway of the innate immune response, as demonstrated in experiments with TLR4-deficient and MyD88-knockout mice. TLR2-dependent signaling did not play a major role in early protection. In addition, this study also shows that even at high doses, BPZE1 is safe in the severely immunocompromised MyD88-deficient mice, whereas virulent B. pertussis caused a severe pathological condition and death in these mice, even at a low dose. Finally, coadministration of virulent B. pertussis with BPZE1 did not cause exacerbated outgrowth of the virulent strain, thereby adding to the safety profile of this live vaccine candidate.<\/jats:p>","DOI":"10.4049\/jimmunol.1901102","type":"journal-article","created":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T22:30:34Z","timestamp":1573857034000},"page":"3293-3300","source":"Crossref","is-referenced-by-count":21,"title":["Early Protection against Pertussis Induced by Live Attenuated <i>Bordetella pertussis<\/i> BPZE1 Depends on TLR4"],"prefix":"10.1093","volume":"203","author":[{"given":"Anne-Sophie","family":"Debrie","sequence":"first","affiliation":[{"name":"Centre d\u2019Infection et Immunit\u00e9 de Lille, CNRS UMR8204\u2013INSERM U1019, Institut Pasteur de Lille , F-59019 Lille ,","place":["France"]},{"name":"Centre Hospitalier Universitaire de Lille, Universit\u00e9 de Lille , 59000 Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5968-9442","authenticated-orcid":false,"given":"Nathalie","family":"Mielcarek","sequence":"additional","affiliation":[{"name":"Centre d\u2019Infection et Immunit\u00e9 de Lille, CNRS UMR8204\u2013INSERM U1019, Institut Pasteur de Lille , F-59019 Lille ,","place":["France"]},{"name":"Centre Hospitalier Universitaire de Lille, Universit\u00e9 de Lille , 59000 Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Lecher","sequence":"additional","affiliation":[{"name":"Centre d\u2019Infection et Immunit\u00e9 de Lille, CNRS UMR8204\u2013INSERM U1019, Institut Pasteur de Lille , F-59019 Lille ,","place":["France"]},{"name":"Centre Hospitalier Universitaire de Lille, Universit\u00e9 de Lille , 59000 Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Roux","sequence":"additional","affiliation":[{"name":"Centre d\u2019Infection et Immunit\u00e9 de Lille, CNRS UMR8204\u2013INSERM U1019, Institut Pasteur de Lille , F-59019 Lille ,","place":["France"]},{"name":"Centre Hospitalier Universitaire de Lille, Universit\u00e9 de Lille , 59000 Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-4652","authenticated-orcid":false,"given":"Jean-Claude","family":"Sirard","sequence":"additional","affiliation":[{"name":"Centre d\u2019Infection et Immunit\u00e9 de Lille, CNRS UMR8204\u2013INSERM U1019, Institut Pasteur de Lille , F-59019 Lille ,","place":["France"]},{"name":"Centre Hospitalier Universitaire de Lille, Universit\u00e9 de Lille , 59000 Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Locht","sequence":"additional","affiliation":[{"name":"Centre d\u2019Infection et Immunit\u00e9 de Lille, CNRS UMR8204\u2013INSERM U1019, Institut Pasteur de Lille , F-59019 Lille ,","place":["France"]},{"name":"Centre Hospitalier Universitaire de Lille, Universit\u00e9 de Lille , 59000 Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,15]]},"reference":[{"key":"2025030417544963700_r1","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/S1473-3099(17)30390-0","article-title":"An update of the global burden of pertussis in children younger than 5 years: a modelling study","volume":"17","author":"Yeung","year":"2017","journal-title":"Lancet Infect. 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