{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:08:04Z","timestamp":1789016884206,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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>Background\/Objectives: Pertussis has resurged worldwide despite long-standing vaccination programs. Whole-cell (wP) and acellular (aP) pertussis vaccines differ in immunobiology, durability, reactogenicity, and programmatic use. Poland is the only European Union\/European Economic Area (EU\/EEA) country that routinely primes infants with wP while using aP products for boosters, pregnancy, and selected indications, providing an informative programmatic context. This review compares both platforms across biological, clinical, safety, epidemiological, and supply domains. Methods: We conducted a narrative review of PubMed\/MEDLINE literature and documents from the World Health Organization, European Centre for Disease Prevention and Control, national public health institutes, and regulatory authorities through July 2026. No protocol was registered and no quantitative synthesis was performed. Results: wP priming induces a persistent T-helper 1\/T-helper 17-oriented response and an immunoglobulin G1-dominant profile, whereas aP vaccination produces higher, higher-avidity antibody concentrations, an increasing immunoglobulin G4 fraction, and substantially lower reactogenicity. Historical trials demonstrated marked product-level heterogeneity: efficacy ranged from 36\u201348% for poorly performing wP vaccines to 84\u201385% for multicomponent aP vaccines, while one United Kingdom wP product performed comparably to a five-component aP vaccine. Protection after aP schedules wanes within several years, no validated correlate of protection exists, and neither intramuscular platform reliably prevents colonization or transmission. In 2024, eight aP-using EU\/EEA countries had higher pertussis notification rates than Poland despite stable Polish infant coverage. Conclusions: Neither platform is uniformly superior across products, schedules, and clinically relevant outcomes. Program performance depends primarily on timely infant vaccination, maternal vaccination, appropriate boosters, product-specific effectiveness evidence, and secure vaccine supply.<\/jats:p>","DOI":"10.3390\/vaccines14090775","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:13:25Z","timestamp":1788455605000},"page":"775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Whole-Cell and Acellular Pertussis Vaccines: A Narrative Review of Biological, Clinical, Safety and Programmatic Evidence, with Implications for Poland"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9675-7942","authenticated-orcid":false,"given":"Andrzej","family":"Fal","sequence":"first","affiliation":[{"name":"Collegium Medicum, Cardinal Stefan Wyszynski University, 01-938 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7222-1337","authenticated-orcid":false,"given":"Iwona","family":"Paradowska-Stankiewicz","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology and Surveillance, National Institute of Public Health NIH\u2014National Research Institute, Chocimska 24, 00-791 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Nitsch-Osuch","sequence":"additional","affiliation":[{"name":"Department of Social Medicine and Public Health, Medical University of Warsaw, Pawinskiego 3a, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7883-2427","authenticated-orcid":false,"given":"Ernest","family":"Kuchar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics with Clinical Assessment Unit, Medical University of Warsaw, Zwirki i Wigury 63A, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bricks, L.F., Vargas-Zambrano, J.C., and Macina, D. (2024). Epidemiology of pertussis after the COVID-19 pandemic: Analysis of the factors involved in the resurgence of the disease in high-, middle-, and low-income countries. Vaccines, 12.","DOI":"10.3390\/vaccines12121346"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhang, S., Xu, Y., and Xiao, Y. (2026). Revisiting whooping cough: Global drivers and implications of pertussis resurgence in the acellular vaccine era. Vaccines, 14.","DOI":"10.3390\/vaccines14010035"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2689606","DOI":"10.1080\/14760584.2026.2689606","article-title":"Whole cell and acellular pertussis vaccines\u2014Rethinking the evidence","volume":"25","author":"Casabona","year":"2026","journal-title":"Expert Rev. Vaccines"},{"key":"ref_4","unstructured":"World Health Organization (2015). Pertussis vaccines: WHO position paper\u2014August 2015. Wkly. Epidemiol. Rec., 90, 433\u2013458. Available online: https:\/\/www.who.int\/teams\/immunization-vaccines-and-biologicals\/policies\/position-papers\/pertussis."},{"key":"ref_5","unstructured":"European Centre for Disease Prevention and Control (2026). Pertussis. ECDC Annual Epidemiological Report for 2024, ECDC. Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/pertussis-annual-epidemiological-report-2024."},{"key":"ref_6","unstructured":"European Centre for Disease Prevention and Control (2026). Vaccine Scheduler: Pertussis\u2014Recommended Vaccinations, ECDC. Available online: https:\/\/vaccine-schedule.ecdc.europa.eu\/Scheduler\/ByDisease?SelectedDiseaseId=3&SelectedCountryIdByDisease=-1."},{"key":"ref_7","unstructured":"Chief Sanitary Inspector (2026, August 21). Communication of 31 October 2025 on the Immunization Programme for 2026. Off. J. Minist. Health Repub. Pol.\u00a02025, Item 85, (In Polish)."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1093\/clinids\/9.5.866","article-title":"Reflections on the efficacy of pertussis vaccines","volume":"9","author":"Fine","year":"1987","journal-title":"Rev. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1586\/14760584.3.1.89","article-title":"Toxicity and potency evaluation of pertussis vaccines","volume":"3","author":"Corbel","year":"2004","journal-title":"Expert Rev. Vaccines"},{"key":"ref_10","unstructured":"World Health Organization (2026). Immunization Coverage, WHO. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/immunization-coverage."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"a029553","DOI":"10.1101\/cshperspect.a029553","article-title":"What is wrong with pertussis vaccine immunity? Why immunological memory to pertussis is failing","volume":"9","author":"Diavatopoulos","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_12","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":"Babor","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"van der Lee, S., Hendrikx, L.H., Sanders, E.A.M., Berbers, G.A.M., and Buisman, A.M. (2018). Whole-cell or acellular pertussis primary immunizations in infancy determines adolescent cellular immune profiles. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00051"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e518","DOI":"10.1093\/infdis\/jiae034","article-title":"IL-17 and IFN-\u03b3-producing respiratory tissue-resident memory CD4 T cells persist for decades in adults immunized as children with whole-cell pertussis vaccines","volume":"230","author":"McCarthy","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1128\/CVI.00270-13","article-title":"Differential T- and B-cell responses to pertussis in acellular vaccine-primed versus whole-cell vaccine-primed children 2 years after preschool acellular booster vaccination","volume":"20","author":"Schure","year":"2013","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.vaccine.2017.11.066","article-title":"Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination","volume":"36","author":"Sanders","year":"2018","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/S0264-410X(98)00227-8","article-title":"Levels of anti-pertussis antibodies related to protection after household exposure to Bordetella pertussis","volume":"16","author":"Storsaeter","year":"1998","journal-title":"Vaccine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/S1473-3099(25)00072-6","article-title":"The effect of pertussis vaccination in pregnancy on the immunogenicity of acellular or whole-cell pertussis vaccination in Gambian infants (GaPS): A single-centre, randomised, controlled, double-blind, phase 4 trial","volume":"25","author":"Saso","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.3201\/eid2706.203850","article-title":"Pertactin-deficient Bordetella pertussis, vaccine-driven evolution, and reemergence of pertussis","volume":"27","author":"Ma","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2435134","DOI":"10.1080\/21645515.2024.2435134","article-title":"Pertactin deficiency of Bordetella pertussis: Insights into epidemiology, and perspectives on surveillance and public health impact","volume":"20","author":"Heininger","year":"2024","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/cid\/ciu788","article-title":"Pertactin-negative Bordetella pertussis strains: Evidence for a possible selective advantage","volume":"60","author":"Martin","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/S0140-6736(22)02644-7","article-title":"Immunogenicity and safety of BPZE1, an intranasal live attenuated pertussis vaccine, versus tetanus\u2013diphtheria\u2013acellular pertussis vaccine: A randomised, double-blind, phase 2b trial","volume":"401","author":"Keech","year":"2023","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101211","DOI":"10.1016\/j.lanmic.2025.101211","article-title":"Efficacy, immunogenicity, and safety of the live attenuated nasal pertussis vaccine, BPZE1, in the UK: A randomised, placebo-controlled, phase 2b trial using a controlled human infection model with virulent Bordetella pertussis","volume":"6","author":"Gbesemete","year":"2025","journal-title":"Lancet Microbe"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1056\/NEJM199602083340601","article-title":"A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis","volume":"334","author":"Greco","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1056\/NEJM199602083340602","article-title":"A controlled trial of a two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine","volume":"334","author":"Gustafsson","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/S0140-6736(97)06508-2","article-title":"Randomised controlled trial of two-component, three-component, and five-component acellular pertussis vaccines compared with whole-cell pertussis vaccine","volume":"350","author":"Olin","year":"1997","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/S0264-410X(97)00100-X","article-title":"A randomized double-blind trial comparing a two-component acellular to a whole-cell pertussis vaccine in Senegal","volume":"15","author":"Simondon","year":"1997","journal-title":"Vaccine"},{"key":"ref_29","first-page":"CD001478","article-title":"Acellular vaccines for preventing whooping cough in children","volume":"9","author":"Zhang","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7270","DOI":"10.1016\/j.vaccine.2018.10.028","article-title":"Recommendations to control pertussis prioritized relative to economies: A Global Pertussis Initiative update","volume":"36","author":"Forsyth","year":"2018","journal-title":"Vaccine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1056\/NEJMoa1200850","article-title":"Waning protection after fifth dose of acellular pertussis vaccine in children","volume":"367","author":"Klein","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1542\/peds.2014-3358","article-title":"Tdap vaccine effectiveness in adolescents during the 2012 Washington State pertussis epidemic","volume":"135","author":"Acosta","year":"2015","journal-title":"Pediatrics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1716","DOI":"10.1542\/peds.2012-3836","article-title":"Comparative effectiveness of acellular versus whole-cell pertussis vaccines in teenagers","volume":"131","author":"Klein","year":"2013","journal-title":"Pediatrics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1586\/14760584.2014.944167","article-title":"Waning vaccine immunity in teenagers primed with whole cell and acellular pertussis vaccine: Recent epidemiology","volume":"13","author":"Sheridan","year":"2014","journal-title":"Expert Rev. Vaccines"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6067","DOI":"10.1016\/j.vaccine.2021.08.105","article-title":"Duration of protection against Bordetella pertussis infection elicited by whole-cell and acellular vaccine priming in Polish children and adolescents","volume":"39","author":"Rumik","year":"2021","journal-title":"Vaccine"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"P\u00e9rez Chac\u00f3n, G., Estcourt, M.J., Totterdell, J., Marsh, J.A., Perrett, K.P., Campbell, D.E., Wood, N., Gold, M., Waddington, C.S., and McIntyre, P. (2024). Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants (OPTIMUM): A randomised, double-blind, noninferiority trial. PLoS Med., 21.","DOI":"10.1371\/journal.pmed.1004414"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1001\/jamapediatrics.2016.0047","article-title":"Epidemiological and economic effects of priming with the whole-cell Bordetella pertussis vaccine","volume":"170","author":"DeAngelis","year":"2016","journal-title":"JAMA Pediatr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6007","DOI":"10.1016\/j.vaccine.2018.08.022","article-title":"Comparison of adverse events following immunisation with acellular and whole-cell pertussis vaccines: A systematic review","volume":"36","author":"Patterson","year":"2018","journal-title":"Vaccine"},{"key":"ref_39","unstructured":"Institute of Medicine (US) Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines, Howson, C.P., Howe, C.J., and Fineberg, H.V. (1991). Adverse Effects of Pertussis and Rubella Vaccines, National Academies Press."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/S1474-4422(06)70446-X","article-title":"De-novo mutations of the sodium channel gene SCN1A in alleged vaccine encephalopathy: A retrospective study","volume":"5","author":"Berkovic","year":"2006","journal-title":"Lancet Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1097\/01.inf.0000130075.56368.02","article-title":"Lack of evidence of encephalopathy related to pertussis vaccine: Active surveillance by IMPACT, Canada, 1993\u20132002","volume":"23","author":"Moore","year":"2004","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/j.1442-200x.2004.01970.x","article-title":"Safety and efficacy of acellular pertussis vaccine in Japan, evaluated by 23 years of its use for routine immunization","volume":"46","author":"Kimura","year":"2004","journal-title":"Pediatr. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/S0140-6736(14)60686-3","article-title":"Effectiveness of maternal pertussis vaccination in England: An observational study","volume":"384","author":"Amirthalingam","year":"2014","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1016\/j.ajog.2025.11.025","article-title":"Effectiveness of 5-pertussis-component tetanus, diphtheria, and acellular pertussis (Tdap5) vaccination in pregnancy at preventing infant pertussis","volume":"234","author":"Hsiao","year":"2026","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_45","unstructured":"Centers for Disease Control and Prevention (2026, August 21). Pertussis Vaccine Recommendations, Available online: https:\/\/www.cdc.gov\/pertussis\/hcp\/vaccine-recommendations\/index.html."},{"key":"ref_46","unstructured":"European Centre for Disease Prevention and Control (2024). Increase of Pertussis Cases in the EU\/EEA, 8 May 2024, ECDC."},{"key":"ref_47","unstructured":"European Centre for Disease Prevention and Control (2020). Pertussis. ECDC Annual Epidemiological Report for 2018, ECDC. Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/pertussis-annual-epidemiological-report-2018."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/S0140-6736(97)04334-1","article-title":"Impact of anti-vaccine movements on pertussis control: The untold story","volume":"351","author":"Gangarosa","year":"1998","journal-title":"Lancet"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4161","DOI":"10.1016\/j.vaccine.2015.04.036","article-title":"Vaccine hesitancy: Definition, scope and determinants","volume":"33","author":"MacDonald","year":"2015","journal-title":"Vaccine"},{"key":"ref_50","unstructured":"National Institute of Public Health NIH\u2014National Research Institute (2026, August 21). What Is the Number of Recorded Instances of Non-Compliance with Mandatory Vaccination?, (In Polish)."},{"key":"ref_51","first-page":"1409","article-title":"Does the morbidity on pertussis depend on the type and number of vaccines used to immunize? Analysis of data from epidemiological surveillance in 2012\u20132016","volume":"71","year":"2018","journal-title":"Wiad. Lek."},{"key":"ref_52","unstructured":"Supreme Audit Office (2026, August 25). System of Preventive Vaccinations for Children, (In Polish)."},{"key":"ref_53","unstructured":"European Centre for Disease Prevention and Control (2016). Rapid Risk Assessment: Shortage of Acellular Pertussis-Containing Vaccines and Impact on Immunisation Programmes in the EU\/EEA\u2014First Update, 3 February 2016, ECDC."},{"key":"ref_54","unstructured":"National Institute of Public Health NIH\u2014National Research Institute (2026, August 25). Pertussis Vaccine, (In Polish)."},{"key":"ref_55","unstructured":"Institute of Biotechnology of Sera and Vaccines BIOMED S.A. (2026, August 25). DTP\u2014Diphtheria-Tetanus-Pertussis Vaccine. Available online: https:\/\/biomed.pl\/en\/products\/dtp\/."},{"key":"ref_56","unstructured":"Ministry of Health, Republic of Poland (2026, August 25). Pertussis Vaccine for Pregnant Women, (In Polish)."},{"key":"ref_57","unstructured":"National Health Fund (2026, August 25). Vaccinations in Pharmacies 2026\u2014Full List of Adult Vaccinations Financed by the National Health Fund, (In Polish)."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/9\/775\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:21:00Z","timestamp":1789014060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/9\/775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":57,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["vaccines14090775"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14090775","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}