{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T01:28:56Z","timestamp":1782955736191,"version":"3.54.5"},"reference-count":108,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Whooping cough, or pertussis, mostly caused by Bordetella pertussis, is a respiratory disease that affects all age groups, but severe and fatal pertussis occurs almost exclusively in young children. The widespread use of whole-cell and, more recently, of acellular vaccines has substantially reduced the disease incidence. However, it has not been eliminated in any part of the world and has made a worrisome rebound in several areas. Cocoon and maternal immunization have been implemented in several countries but have their intrinsic limitations. To effectively control pertussis, novel vaccines are needed that protect against disease and prevent B. pertussis infection and transmission, which is not the case for current vaccines. Several approaches are contemplated, including alternative administration routes, such as nasal immunization, improvement of acellular vaccines by adding more antigens and T-cell-promoting adjuvants, and the development of novel vaccines, such as outer membrane vesicles and live attenuated vaccines. Among them, only a live attenuated vaccine has so far been assessed for safety and immunogenicity in preclinical models other than mice and is in clinical development. Before any of these vaccines can be used in neonates, extensive safety and immunogenicity assessment in pre-clinical neonatal models and in carefully designed clinical trials is necessary. The aim of this review is to discuss the current pertussis problem, implemented strategies to resolve it, the value of animal models and novel vaccine approaches.<\/jats:p>","DOI":"10.3390\/vaccines9030228","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T11:46:09Z","timestamp":1614944769000},"page":"228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Path to New Pediatric Vaccines against Pertussis"],"prefix":"10.3390","volume":"9","author":[{"given":"Camille","family":"Locht","sequence":"first","affiliation":[{"name":"Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1128\/CMR.18.2.326-382.2005","article-title":"Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due to Bordetella pertussis and Other Bordetella Subspecies","volume":"18","author":"Mattoo","year":"2005","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1056\/NEJMcp041025","article-title":"Pertussis\u2014not just for kids","volume":"352","author":"Hewlett","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/S1473-3099(02)00452-8","article-title":"Pertussis of adults and infants","volume":"2","author":"Halperin","year":"2002","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1093\/infdis\/132.6.707","article-title":"Can Whooping Cough Be Eradicated?","volume":"132","author":"Kendrick","year":"1975","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1093\/clinids\/1.6.927","article-title":"An evaluation of pertussis vaccine","volume":"1","author":"Mortimer","year":"1979","journal-title":"Rev. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S107","DOI":"10.1086\/515057","article-title":"Pertussis in the Preantibiotic and Prevaccine Era, with Emphasis on Adult Pertussis","volume":"28","author":"Cherry","year":"1999","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"763","DOI":"10.2307\/4579202","article-title":"Age incidence of the common communicable diseases of children: A study of case rates among all children and among children not previously attacked and of death rates and the estimated case fatality","volume":"44","author":"Collins","year":"1929","journal-title":"Public Health Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/S0140-6736(82)92214-0","article-title":"The Recurrence of Whooping Cough: Possible Implications for Assessment of Vaccine Efficacy","volume":"319","author":"Fine","year":"1982","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/S0022-3476(34)80039-X","article-title":"Pertussis in adults","volume":"5","author":"Mannerstedt","year":"1934","journal-title":"J. Pediatr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1128\/CMR.00083-15","article-title":"Pertussis: Microbiology, Disease, Treatment, and Prevention","volume":"29","author":"Kilgore","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_11","unstructured":"World Health Organization (2021, March 01). Immunization Coverage with DTP3 Vaccines in Infants (from <50%). Available online: http:\/\/www.who.int\/immunization\/monitoring_surveillance\/burden\/vpd\/surveillance_type\/passive\/big_dtp3_map_global_coverage.jpg."},{"key":"ref_12","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. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chiappini, E., Stival, A., Galli, L., and De Martino, M. (2013). Pertussis re-emergence in the post-vaccination era. BMC Infect. Dis., 13.","DOI":"10.1186\/1471-2334-13-151"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1093\/infdis\/jit491","article-title":"Pertussis resurgence: Perspectives from the working group meeting on pertussis on the causes, possible paths forward, and gaps in our knowledge","volume":"209","author":"Burns","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.3389\/fimmu.2019.01344","article-title":"Pertussis Prevention: Reasons for Resurgence, and Differences in the Current Acellular Pertussis Vaccines","volume":"10","author":"Esposito","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s12916-015-0382-8","article-title":"Asymptomatic transmission and the resurgence of Bordetella pertussis","volume":"13","author":"Althouse","year":"2015","journal-title":"BMC Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1056\/NEJM196510282731804","article-title":"Immunization and Antibody Response in the Newborn Infant","volume":"273","author":"Provenzano","year":"1965","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.jpeds.2008.03.011","article-title":"Poor immune responses to a birth dose of diphtheria, tetanus, and acellular pertussis vaccine","volume":"153","author":"Halasa","year":"2008","journal-title":"J. Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.jpeds.2007.09.034","article-title":"Neonatal vaccination with an acellular pertussis vaccine accelerates the acquisition of pertussis antibodies in infants","volume":"152","author":"Knuf","year":"2008","journal-title":"J. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1542\/peds.111.5.1042","article-title":"Immunogenicity of a Three-Component Acellular Pertussis Vaccine Administered at Birth","volume":"111","author":"Belloni","year":"2003","journal-title":"Pediatrics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1001\/jamapediatrics.2018.2349","article-title":"Immunogenicity and safety of monovalent acellular pertussis vaccine at birth. A randomized clinical trial","volume":"172","author":"Wood","year":"2018","journal-title":"JAMA Pediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/01.inf.0000258699.64164.6d","article-title":"Transmission of Bordetella pertussis to Young Infants","volume":"26","author":"Wendelboe","year":"2007","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Urwyler, P., and Heininger, U. (2014). Protecting newborns from pertussis\u2014The challenge of complete cocooning. BMC Infect. Dis., 14.","DOI":"10.1186\/1471-2334-14-397"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1016\/j.vaccine.2015.02.051","article-title":"Uptake of a government-funded pertussis-containing booster vaccination program for parents of new babies in Victoria, Australia","volume":"33","author":"Rowe","year":"2015","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/INF.0000000000000486","article-title":"Evaluation of the Impact of a Pertussis Cocooning Program on Infant Pertussis Infection","volume":"34","author":"Healy","year":"2015","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1073\/pnas.1314688110","article-title":"Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model","volume":"111","author":"Warfel","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Holubov\u00e1, J., Stan\u011bk, O., Br\u00e1zdilov\u00e1, L., Ma\u0161\u00edn, J., Bumba, L., Gorringe, A.R., Alexander, F., and \u0160ebo, P. (2020). Acellular Pertussis Vaccine Inhibits Bordetella pertussis Clearance from the Nasal Mucosa of Mice. Vaccines, 8.","DOI":"10.3390\/vaccines8040695"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41541-020-00270-8","article-title":"Suppression of mucosal Th17 memory response by acellular pertussis vaccines enhances nasal Bordetella pertussis carriage","volume":"6","author":"Dubois","year":"2020","journal-title":"NPJ Vaccines"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/22221751.2018.1564630","article-title":"Immunization with whole cell but not acellular pertussis vaccines primes CD4 TRM cells that sustain protective immunity against nasal colonization with Bordetella pertussis","volume":"8","author":"Wilk","year":"2019","journal-title":"Emerg. Microbes. Infect."},{"key":"ref_30","first-page":"235","article-title":"Vaccination during pregnancy: Current and possible future recommendations","volume":"179","author":"Maertens","year":"2020","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1186\/s12884-020-03243-w","article-title":"Maternal vaccinations coverage and reasons for non-compliance\u2014A cross-sectional observational study","volume":"20","author":"Drezner","year":"2020","journal-title":"BMC Pregnancy Childbirth"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.15585\/mmwr.mm6738a3","article-title":"Influenza and Tdap Vaccination Coverage Among Pregnant Women\u2014United States, April 2018","volume":"67","author":"Kahn","year":"2018","journal-title":"MMWR. Morb. Mortal. Wkly. Rep."},{"key":"ref_33","first-page":"580","article-title":"The effect of maternal antibody on the serologic response and the incidence of adverse reactions after primary immunization with acellular and whole-cell pertussis vaccines combined with diphtheria and tetanus toxoids","volume":"96","author":"Englund","year":"1995","journal-title":"Pediatrics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1093\/cid\/ciz778","article-title":"Quantity and Quality of Antibodies After Acellular Versus Whole-cell Pertussis Vaccines in Infants Born to Mothers Who Received Tetanus, Diphtheria, and Acellular Pertussis Vaccine During Pregnancy: A Randomized Trial","volume":"71","author":"Wanlapakorn","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1126\/science.7063839","article-title":"Directly transmitted infectious diseases: Control by vaccination","volume":"215","author":"Anderson","year":"1982","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/cid\/ciz842","article-title":"Toward a Controlled Human Infection Model of Pertussis","volume":"71","author":"Merkel","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/mi.2012.54","article-title":"Immunity to the respiratory pathogen Bordetella pertussis","volume":"5","author":"Higgs","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.tim.2007.09.003","article-title":"The benefits of using diverse animal models for studying pertussis","volume":"15","author":"Elahi","year":"2007","journal-title":"Trends Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1128\/IAI.06310-11","article-title":"Nonhuman Primate Model of Pertussis","volume":"80","author":"Warfel","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"803","DOI":"10.2105\/AJPH.37.7.803-b","article-title":"Mouse protection tests in the study of pertussis vaccine: A comparative series using the intracerebral route for challenge","volume":"37","author":"Kendrick","year":"1947","journal-title":"Am. J. Public Health"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.2105\/AJPH.55.9.1451","article-title":"History of the antigen committees of the American Public Health Association","volume":"55","author":"Bunney","year":"1965","journal-title":"Am. J. Public Health Nations Health"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1128\/IAI.66.2.594-602.1998","article-title":"A murine model in which protection correlates with pertussis vaccine efficacy in children reveals complementary roles for humoral and cell-mediated immunity in protection against Bordetella pertussis","volume":"66","author":"Mills","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1128\/jcm.32.11.2851-2853.1994","article-title":"Unexpected isolation of Bordetella pertussis from a blood culture","volume":"32","author":"Janda","year":"1994","journal-title":"J. Clin. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1016\/j.jinf.2005.04.014","article-title":"Isolation of Bordetella pertussis in blood culture from a patient with multiple myeloma","volume":"52","author":"Jonassen","year":"2006","journal-title":"J. Infect."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1084\/jem.186.11.1843","article-title":"Atypical disease after Bordetella pertussis respiratory infection of mice with targeted disruptions of interferon-gamma receptor or immunoglobulin \u00b5 chain genes","volume":"186","author":"Mahon","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.3389\/fimmu.2018.03068","article-title":"The Role of Mucosal Immunity in Pertussis","volume":"9","author":"Solans","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1038\/s41385-018-0073-9","article-title":"IL-17-dependent SIgA-mediated protection against nasal Bordetella pertussis infection by live attenuated BPZE1 vaccine","volume":"11","author":"Solans","year":"2018","journal-title":"Mucosal Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"233","DOI":"10.4049\/jimmunol.1602051","article-title":"Lung CD4 Tissue-Resident Memory T Cells Mediate Adaptive Immunity Induced by Previous Infection of Mice withBordetella pertussis","volume":"199","author":"Wilk","year":"2017","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1093\/infdis\/jis443","article-title":"Airborne Transmission of Bordetella pertussis","volume":"206","author":"Warfel","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1172\/JCI121309","article-title":"Th1\/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters","volume":"128","author":"Antunes","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/mi.2012.117","article-title":"Bordetella pertussis infection induces a mucosal IL-17 response and long-lived Th17 and Th1 immune memory cells in nonhuman primates","volume":"6","author":"Warfel","year":"2013","journal-title":"Mucosal Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1093\/infdis\/jiu090","article-title":"Maternal and Neonatal Vaccination Protects Newborn Baboons From Pertussis Infection","volume":"210","author":"Warfel","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/infdis\/jiy022","article-title":"Maternal vaccination with a monocomponent pertussis toxoid vaccine is sufficient to protect infants in a baboon model of whooping cough","volume":"217","author":"Kapil","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"eaay9258","DOI":"10.1126\/sciadv.aay9258","article-title":"Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons","volume":"6","author":"Nguyen","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wearing, H.J., and Rohani, P. (2009). Estimating the Duration of Pertussis Immunity Using Epidemiological Signatures. PLOS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000647"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.coi.2015.05.008","article-title":"Pertussis vaccines and the challenge of inducing durable immunity","volume":"35","author":"Warfel","year":"2015","journal-title":"Curr. Opin. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chasaide, C.N., and Mills, K.H.G. (2020). Next-generation pertussis vaccines based on the induction of protective T cells in the respiratory tract. Vaccines, 8.","DOI":"10.3390\/vaccines8040621"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Dewan, K.K., Linz, B., DeRocco, S.E., and Harvill, E.T. (2020). Acellular Pertussis Vaccine Components: Today and Tomorrow. Vaccines, 8.","DOI":"10.3390\/vaccines8020217"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/5584_2019_407","article-title":"New Pertussis Vaccines: A Need and a Challenge","volume":"1183","author":"Hozbor","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5460","DOI":"10.1016\/j.vaccine.2017.11.055","article-title":"Will we have new pertussis vaccines?","volume":"36","author":"Locht","year":"2018","journal-title":"Vaccine"},{"key":"ref_61","first-page":"S1198","article-title":"Safety and immunogenicity of the epicutaneous reactivation of pertussis toxin immunity iin healthy adults: A phase I, randomized, double-blind, placebo-controlled trial","volume":"5","author":"Chatzis","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_62","first-page":"146","article-title":"Needle-free and adjuvant-free epicutaneous boosting of pertussis immunity: Preclinical proof of concept","volume":"33","author":"Gallivet","year":"2015","journal-title":"Vaccine"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1017\/S0022172400024293","article-title":"Respiratory and humoral immune response to aerosol and intramuscular pertussis vaccine","volume":"74","author":"Thomas","year":"1975","journal-title":"J. Hyg."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1099\/0022-1317-49-2-157","article-title":"A nasal whole-cell pertussis vaccine induces specific systemic and cross-reactive mucosal antibody responses in human volunteers","volume":"49","author":"Berstad","year":"2000","journal-title":"J. Med. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6270","DOI":"10.1128\/IAI.67.12.6270-6280.1999","article-title":"Mutants of Escherichia coli heat-labile toxin act as effective mucosal adjuvants for nasal delivery of an acellular pertussis vaccine: Differential effects of the nontoxic AB complex and enzyme activity on Th1 and Th2 cells","volume":"67","author":"Ryan","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1056\/NEJMp048006","article-title":"Nasal vaccination, Escherichia coli enterotoxin, and Bell\u2019s palsy","volume":"350","author":"Couch","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.imlet.2018.03.012","article-title":"Novel intranasal pertussis vaccine based on bacterium-like particles as a mucosal adjuvant","volume":"198","author":"Shi","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41541-019-0136-2","article-title":"Intranasal acellular pertussis vaccine provides mucosal immunity and protects mice from Bordetella pertussis","volume":"4","author":"Boehm","year":"2019","journal-title":"npj Vaccines"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1038\/s41385-018-0080-x","article-title":"Sustained protective immunity against Bordetella pertussis nasal colonization by intranasal immunization with a vaccine-adjuvant combination that induces IL-17-secreting TRM cells","volume":"11","author":"Allen","year":"2018","journal-title":"Mucosal. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ross, P.J., Sutton, C.E., Higgins, S., Allen, A.C., Walsh, K., Misiak, A., Lavelle, E.D., McLoughlin, R.M., and Mills, K.H.G. (2013). Relative contribution of Th1 and Th17 cells in adaptive immunity to Bordetella pertussis: Towards the rational design of an improved acellular pertussis vaccine. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1003264"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5256","DOI":"10.1016\/j.vaccine.2017.08.009","article-title":"Addition of TLR7 agonist to an acellular pertussis vaccine enhances Th1 and T17 responses and protective immunity in a mouse model","volume":"35","author":"Misiak","year":"2017","journal-title":"Vaccine"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.vaccine.2007.12.012","article-title":"Supplementation of whole-cell pertussis vaccines with lipopolysaccharide analogs: Modification of vaccine-induced immune responses","volume":"26","author":"Geurtsen","year":"2008","journal-title":"Vaccine"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejpb.2016.05.013","article-title":"The preparation and characterization of PLG nanoparticles with an entrapped synthetic TLR7 agonist and their preclinical evaluation as adjuvant for an adsorbed DTaP vaccine","volume":"105","author":"Bruno","year":"2016","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ijpharm.2016.08.059","article-title":"PGLA nano\/micro particles encapsulated with pertussis toxoid (PTd) enhances Th1\/Th17 immune responses in a murine model","volume":"513","author":"Li","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1097\/00006454-199705000-00012","article-title":"The best acellular pertussis vaccines are multi-component","volume":"16","author":"Olin","year":"1997","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.vaccine.2018.11.028","article-title":"Increasing FIM2\/3 antigen-content improves efficacy of Bordetella pertussis vaccines in mice in vivo without altering vaccine-induced human reactogenicity biomarkers in vitro","volume":"37","author":"Queenan","year":"2019","journal-title":"Vaccine"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Fedele, G., Schiavoni, I., Adkins, I., Klimova, N., and Sebo, P. (2017). Invasion of Dendritic Cells, Macrophages and Neutrophils by the Bordetella Adenylate Cyclase Toxin: A Subversive Move to Fool Host Immunity. Toxins, 9.","DOI":"10.3390\/toxins9100293"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e00857-17","DOI":"10.1128\/IAI.00857-17","article-title":"Evaluation of adenylate cyclase toxin antigen in acellular pertussis vaccines by using a Bordetella pertussis challenge model in mice","volume":"86","author":"Boehm","year":"2018","journal-title":"Infect. Immun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4306","DOI":"10.1016\/j.vaccine.2008.06.017","article-title":"Protective activity of the Bordetella pertussis BrkA autotransporter in the murine lung colonization model","volume":"26","author":"Marr","year":"2008","journal-title":"Vaccine"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/1348-0421.12504","article-title":"Protective effects of in vivo -expressed autotransporters against Bordetella pertussis infection","volume":"61","author":"Suzuki","year":"2017","journal-title":"Microbiol. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.3389\/fimmu.2020.01879","article-title":"Canonical and Noncanonical Inflammasome Activation by Outer Membrane Vesicles Derived From Bordetella pertussis","volume":"11","author":"Elizagaray","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jconrel.2018.07.035","article-title":"Development of a thermostable spray dried outer membrane vesicle pertussis vaccine for pulmonary immunization","volume":"286","author":"Kanojia","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.1016\/j.vaccine.2008.07.004","article-title":"Outer membrane vesicles as acellular vaccine against pertussis","volume":"26","author":"Roberts","year":"2008","journal-title":"Vaccine"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"38240","DOI":"10.1038\/srep38240","article-title":"Bordetella pertussis outer membrane vesicle vaccine confers equal efficacy in mice with milder inflammatory responses compared to whole-cell vaccine","volume":"6","author":"Raeven","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1016\/j.vaccine.2010.12.068","article-title":"Outer membrane vesicles obtained from Bordetella pertussis Tohama expressing the lipid A deacylase PagL as a novel acellular vaccine candidate","volume":"29","author":"Asensio","year":"2011","journal-title":"Vaccine"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.vaccine.2013.12.048","article-title":"Acellular pertussis vaccine based on outer membrane vesicles capable of conferring both long-lasting immunity and protection against different strain genotypes","volume":"32","author":"Gaillard","year":"2014","journal-title":"Vaccine"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.mib.2019.01.002","article-title":"The BvgASR virulence regulon of Bordetella pertussis","volume":"47","author":"Chen","year":"2019","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Raeven, R.H.M., Van Vlies, N., Salverda, M.L.M., Van Der Maas, L., Uittenbogaard, J.P., Bindels, T.H.E., Rigters, J., Verhagen, L.M., Kruijer, S., and Van Riet, E. (2020). The Role of Virulence Proteins in Protection Conferred by Bordetella pertussis Outer Membrane Vesicle Vaccines. Vaccines, 8.","DOI":"10.3390\/vaccines8030429"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-63998-2","article-title":"Intranasal immunization with outer membrane vesicle pertussis vaccine confers broad protection through mucosal IgA and Th17 responses","volume":"10","author":"Raeven","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3389\/fcimb.2019.00125","article-title":"A pertussis outer membrane vesicle-based vaccine induces lung-resident memory CD4 T cells and protection against Bordetella pertussis, including pertactin deficient strains","volume":"9","author":"Zurita","year":"2019","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1128\/iai.58.3.732-739.1990","article-title":"Construction and characterization in vivo of Bordetella pertussis aroA mutants","volume":"58","author":"Roberts","year":"1990","journal-title":"Infect. Immun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"856","DOI":"10.4014\/jmb.1108.08003","article-title":"Construction and preliminary immunobiological characterization of a novel, non-reverting, intranasal live attenuated whooping cough vaccine candidate","volume":"22","author":"Daggard","year":"2012","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Mielcarek, N., Debrie, A.-S., Raze, D., Bertout, J., Rouanet, C., Ben Younes, A., Creusy, C., Engle, J., Goldman, E.W., and Locht, C. (2006). Live Attenuated B. pertussis as a Single-Dose Nasal Vaccine against Whooping Cough. PLoS Pathog., 2.","DOI":"10.1371\/journal.ppat.0020065"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3293","DOI":"10.4049\/jimmunol.1901102","article-title":"Early Protection against Pertussis Induced by Live Attenuated Bordetella pertussis BPZE1 Depends on TLR","volume":"203","author":"Debrie","year":"2019","journal-title":"J. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"7105","DOI":"10.1128\/JVI.02542-09","article-title":"Attenuated Bordetella pertussis Protects against Highly Pathogenic Influenza A Viruses by Dampening the Cytokine Storm","volume":"84","author":"Li","year":"2010","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1164\/rccm.201307-1227OC","article-title":"Attenuated Bordetella pertussis vaccine protects against respiratory syncytial virus disease via an IL-17-dependent mechanism","volume":"189","author":"Roux","year":"2014","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"ref_97","unstructured":"Blecher, T., Kammoun, H., Coutte, L., Debrie, A.S., Mielcarek, N., Sirard, J.C., Cauchi, S., and Locht, C. (2018). Live attenuated Bordetella pertussis vaccine candidate BPZE1 transiently protects against lethal pneumococcal disease in mice. Vaccine, in press."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.3389\/fimmu.2018.02872","article-title":"Non-specific effects of live attenuated pertussis vaccine against heterologous infectious and inflammatory diseases","volume":"9","author":"Cauchi","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1128\/CVI.00082-09","article-title":"A live attenuated Bordetella pertussis candidate vaccine does not cause disseminating infection in gamma interferon receptor knockout mice","volume":"16","author":"Skerry","year":"2009","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5722","DOI":"10.1016\/j.vaccine.2008.08.018","article-title":"Genetic stability of the live attenuated Bordetella pertussis vaccine candidate BPZE1","volume":"26","author":"Feunou","year":"2008","journal-title":"Vaccine"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Thalen, M., Debrie, A.-S., Coutte, L., Raze, D., Solovay, K., Rubin, K., Mielcarek, N., and Locht, C. (2020). Manufacture of a Stable Lyophilized Formulation of the Live Attenuated Pertussis Vaccine BPZE1. Vaccines, 8.","DOI":"10.3390\/vaccines8030523"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1093\/infdis\/jix254","article-title":"Live Attenuated Pertussis Vaccine BPZE1 Protects Baboons Against Bordetella pertussis Disease and Infection","volume":"216","author":"Locht","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"312","DOI":"10.36233\/0372-9311-2020-97-4-3","article-title":"Preclinical studies of safety, immunogenicity and protective activity of attenuated Bordetella pertussis bacteria on the rhesus macaque model","volume":"97","author":"Medkova","year":"2020","journal-title":"J. Microbiol. Epidemiol. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Thorstensson, R., Trollfors, B., Al-Tawil, N., Jahnmatz, M., Bergstr\u00f6m, J., Ljungman, M., T\u00f6rner, A., Wehlin, L., Van Broekhoven, A., and Bosman, F. (2014). A phase I clinical study of a live attenuated Bordetella pertussis vaccine\u2014BPZE1; a single centre, double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally to healthy adult male vol-unteers. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0083449"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/S1473-3099(20)30274-7","article-title":"Safety and immunogenicity of the live attenuated intranasal pertussis vaccine BPZE1: A phase 1b, double-blind, randomised, placebo-controlled dose-escalation study","volume":"20","author":"Jahnmatz","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1172\/JCI135020","article-title":"Live attenuated pertussis vaccine BPZE1 induces a broad antibody response in humans","volume":"130","author":"Lin","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.4049\/jimmunol.170.3.1504","article-title":"Bordetella pertussisInfection in 2-Month-Old Infants Promotes Type 1 T Cell Responses","volume":"170","author":"Mascart","year":"2003","journal-title":"J. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/S0140-6736(06)68507-3","article-title":"Effect of BCG vaccination on childhood tuberculous meningitis and military tuberculosis worldwide: A meta-analysis and assessment of cost-effectiveness","volume":"367","author":"Fine","year":"2006","journal-title":"Lancet"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/3\/228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:33:48Z","timestamp":1760160828000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/3\/228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":108,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["vaccines9030228"],"URL":"https:\/\/doi.org\/10.3390\/vaccines9030228","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]}}}