Mucosal IgA Antibodies are Critical for Bacterial Clearance of Bordetella pertussis in the Baboon Model
Main Article Content
Abstract
Background: Despite the control of Bordetella pertussis with vaccine introduction, the incidence of pertussis has increased in the United States and globally. New vaccine strategies are clearly needed to regain control of this vaccine-preventable infection.
Methods: Experimental pertussis infection of baboons induces an acute respiratory illness with clinical and laboratory features similar to whooping cough in man. In a previous study, acellular pertussis-vaccinated (aP) baboons were protected from clinical illness but not from prolonged airway colonization. In contrast, convalescent baboons are protected from both clinical illness and colonization. These studies suggest that current aP vaccines may be ineffective at preventing airway colonization, contributing to resurgence of pertussis.
Results: In studies conducted at the University of Massachusetts Chan Medical School in Worcester, Massachusetts, mucosal IgG antibody responses in nasopharyngeal washes are similar in convalescent and vaccinated baboons. However, significantly higher mucosal anti-pertussis immunoglobulin A (IgA) responses are observed in convalescent animals.
Conclusions: These studies suggest that mucosal IgA responses to some pertussis antigens will result in bacterial clearance.
Downloads
Article Details

This work is licensed under a Creative Commons Attribution 4.0 International License.
Pathogens and Immunity abides by Creative Commons BY 4.0:
http://creativecommons.org/licenses/by/4.0/
This license lets others distribute, remix, tweak, and build upon your work for any lawful purpose, even commercially, as long as they credit you for the original creation. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials. The authors maintain copyright of their materal.
*Due to a template error on our pdfs, articles published from May 20, 2016 to June 24, 2022 incorrectly state the copyright is held by Pathogens and Immunity. Copyright of all articles is held by the authors of each article as noted in the above copyright policy.
References
1. Kuehn BM. Resurgence of Pertussis Linked With Switch to Acellular Vaccine. JAMA. 2021;326(4):300. doi: http://dx.doi.org/10.1001/jama.2021.11153">10.1001/jama.2021.11153. PubMed PMID: 34313680.
2. Burdin N, Handy LK, Plotkin SA. What Is Wrong with Pertussis Vaccine Immunity? The Problem of Waning Effectiveness of Pertussis Vaccines. Cold Spring Harb Perspect Biol. 2017;9(12). doi: http://dx.doi.org/10.1101/cshperspect.a029454">10.1101/cshperspect.a029454. PubMed PMID: 28289064.
3. Damron FH, Barbier M, Dubey P, Edwards KM, Gu XX, Klein NP, Lu K, Mills KHG, Pasetti MF, Read RC, Rohani P, Sebo P, Harvill ET. Overcoming Waning Immunity in Pertussis Vaccines: Workshop of the National Institute of Allergy and Infectious Diseases. J Immunol. 2020;205(4):877-82. doi: http://dx.doi.org/10.4049/jimmunol.2000676">10.4049/jimmwunol.2000676. PubMed PMID: 32769142; PMCID: PMC7454230.
4. Lesne E, Cavell BE, Freire-Martin I, Persaud R, Alexander F, Taylor S, Matheson M, van Els C, Gorringe A. Acellular Pertussis Vaccines Induce Anti-pertactin Bactericidal Antibodies Which Drives the Emergence of Pertactin-Negative Strains. Front Microbiol. 2020;11:2108. doi: http://dx.doi.org/10.3389/fmicb.2020.02108">10.3389/fmicb.2020.02108. PubMed PMID: 32983069; PMCID: PMC7481377.
5. Queenan AM, Cassiday PK, Evangelista A. Pertactin-negative variants of Bordetella pertussis in the United States. N Engl J Med. 2013;368(6):583-4. doi: http://dx.doi.org/10.1056/NEJMc1209369">10.1056/NEJMc1209369. PubMed PMID: 23388024; PMCID: PMC5115783.
6. Xu Z, Octavia S, Luu LDW, Payne M, Timms V, Tay CY, Keil AD, Sintchenko V, Guiso N, Lan R. Pertactin-Negative and Filamentous Hemagglutinin-Negative Bordetella pertussis, Australia, 2013-2017. Emerg Infect Dis. 2019;25(6):1196-9. doi: http://dx.doi.org/10.3201/eid2506.180240">10.3201/eid2506.180240. PubMed PMID: 31107218; PMCID: PMC6537726.
7. Heininger U, Martini H, Eeuwijk J, Prokic I, Guignard AP, Turriani E, Duchenne M, Berlaimont V. Pertactin deficiency of Bordetella pertussis: Insights into epidemiology, and perspectives on surveillance and public health impact. Hum Vaccin Immunother. 2024;20(1):2435134. doi: http://dx.doi.org/10.1080/21645515.2024.2435134">10.1080/21645515.2024.2435134. PubMed PMID: 39686838; PMCID: PMC11654710.
8. Warfel JM, Beren J, Kelly VK, Lee G, Merkel TJ. Nonhuman primate model of pertussis. Infect Immun. 2012;80(4):1530-6. doi: http://dx.doi.org/10.1128/IAI.06310-11">10.1128/IAI.06310-11. PubMed PMID: 22252879; PMCID: PMC3318410.
9. Warfel JM, Zimmerman LI, Merkel TJ. Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model. Proc Natl Acad Sci U S A. 2014;111(2):787-92. doi: http://dx.doi.org/10.1073/pnas.1314688110">10.1073/pnas.1314688110. PubMed PMID: 24277828; PMCID: PMC3896208.
10. Soumana IH, Linz B, Dewan KK, Sarr D, Gestal MC, Howard LK, Caulfield AD, Rada B, Harvill ET. Modeling Immune Evasion and Vaccine Limitations by Targeted Nasopharyngeal Bordetella pertussis Inoculation in Mice. Emerg Infect Dis. 2021;27(8):2107-16. doi: http://dx.doi.org/10.3201/eid2708.203566">10.3201/eid2708.203566. PubMed PMID: 34286682; PMCID: PMC8314809.
11. Warfel JM, Zimmerman LI, Merkel TJ. Comparison of Three Whole-Cell Pertussis Vaccines in the Baboon Model of Pertussis. Clin Vaccine Immunol. 2016;23(1):47-54. doi: http://dx.doi.org/10.1128/CVI.00449-15">10.1128/CVI.00449-15. PubMed PMID: 26561389; PMCID: PMC4711092.
12. Tuomanen EI, Zapiain LA, Galvan P, Hewlett EL. Characterization of antibody inhibiting adherence of Bordetella pertussis to human respiratory epithelial cells. J Clin Microbiol. 1984;20(2):167-70. doi: http://dx.doi.org/10.1128/jcm.20.2.167-170.1984">10.1128/jcm.20.2.167-170.1984. PubMed PMID: 6092416; PMCID: PMC271278.
13. Hellwig SM, van Spriel AB, Schellekens JF, Mooi FR, van de Winkel JG. Immunoglobulin A-mediated protection against Bordetella pertussis infection. Infect Immun. 2001;69(8):4846-50. doi: http://dx.doi.org/10.1128/IAI.69.8.4846-4850.2001">10.1128/IAI.69.8.4846-4850.2001. PubMed PMID: 11447159; PMCID: PMC98573.
14. Goodman YE, Wort AJ, Jackson FL. Enzyme-linked immunosorbent assay for detection of pertussis immunoglobulin A in nasopharyngeal secretions as an indicator of recent infection. J Clin Microbiol. 1981;13(2):286-92. PubMed PMID: 6259201; PMCID: PMC273779.
15. Thomas G. Respiratory and humoral immune response to aerosol and intramuscular pertussis vaccine. J Hyg (Lond). 1975;74(2):233-7. doi: http://dx.doi.org/10.1017/s0022172400024293">10.1017/s0022172400024293. PubMed PMID: 164502; PMCID: PMC2130377.
16. Kapil P, Wang Y, Gregg K, Zimmerman L, Molano D, Maldonado Villeda J, Sebo P, Merkel TJ. A whole-cell pertussis vaccine engineered to elicit reduced reactogenicity protects baboons against pertussis challenge. mSphere. 2024:e0064724. doi: http://dx.doi.org/10.1128/msphere.00647-24">10.1128/msphere.00647-24. PubMed PMID: 39441011.
17. Galeas-Pena M, Hirsch A, Kuang E, Hoffmann J, Gellings P, Brown JB, Limbert VM, Callahan CL, McLachlan JB, Morici LA. A novel outer membrane vesicle adjuvant improves vaccine protection against Bordetella pertussis. npj Vaccines. 2024;9(1):190. doi: http://dx.doi.org/10.1038/s41541-024-00990-1">10.1038/s41541-024-00990-1.
18. Raeven RH, Brummelman J, Pennings JLA, van der Maas L, Helm K, Tilstra W, van der Ark A, Sloots A, van der Ley P, van Eden W, Jiskoot W, van Riet E, van Els CA, Kersten GF, Han WG, Metz B. Molecular and cellular signatures underlying superior immunity against Bordetella pertussis upon pulmonary vaccination. Mucosal Immunol. 2018;11(3):979-93. doi: http://dx.doi.org/10.1038/mi.2017.81">10.1038/mi.2017.81. PubMed PMID: 28930286.
19. Skerry CM, Mahon BP. A live, attenuated Bordetella pertussis vaccine provides long-term protection against virulent challenge in a murine model. Clin Vaccine Immunol. 2011;18(2):187-93. doi: http://dx.doi.org/10.1128/CVI.00371-10">10.1128/CVI.00371-10. PubMed PMID: 21147936; PMCID: PMC3067348.
20. Solans L, Debrie AS, Borkner L, Aguilo N, Thiriard A, Coutte L, Uranga S, Trottein F, Martin C, Mills KHG, Locht C. IL-17-dependent SIgA-mediated protection against nasal Bordetella pertussis infection by live attenuated BPZE1 vaccine. Mucosal Immunol. 2018;11(6):1753-62. doi: http://dx.doi.org/10.1038/s41385-018-0073-9">10.1038/s41385-018-0073-9. PubMed PMID: 30115992.
21. Keech C, Miller VE, Rizzardi B, Hoyle C, Pryor MJ, Ferrand J, Solovay K, Thalen M, Noviello S, Goldstein P, Gorringe A, Cavell B, He Q, Barkoff A-M, Rubin K, Locht C. Immunogenicity and safety of BPZE1, an intranasal live attenuated pertussis vaccine, versus tetanus–diphtheria–acellular pertussis vaccine: a randomised, double-blind, phase 2b trial. The Lancet. 2023;401(10379):843-55. doi: https://doi.org/10.1016/S0140-6736(22)02644-7">10.1016/S0140-6736(22)02644-7.
22. Locht C, Papin JF, Lecher S, Debrie AS, Thalen M, Solovay K, Rubin K, Mielcarek N. Live Attenuated Pertussis Vaccine BPZE1 Protects Baboons Against Bordetella pertussis Disease and Infection. J Infect Dis. 2017;216(1):117-24. doi: http://dx.doi.org/10.1093/infdis/jix254">10.1093/infdis/jix254. PubMed PMID: 28535276; PMCID: PMC5853371.
23. DeJong MA, Wolf MA, Bitzer GJ, Hall JM, Fitzgerald NA, Pyles GM, Huckaby AB, Petty JE, Lee K, Barbier M, Bevere JR, Ernst RK, Damron FH. BECC438b TLR4 agonist supports unique immune response profiles from nasal and muscular DTaP pertussis vaccines in murine challenge models. Infect Immun. 2024;92(3):e0022323. doi: http://dx.doi.org/10.1128/iai.00223-23">10.1128/iai.00223-23. PubMed PMID: 38323817; PMCID: PMC10929442.
24. Pyles GM, Huckaby AB, Gutierrez Mdl P, Witt WT, Mateu-Borras M, Dublin SR, Rocuskie-Marker C, Sesti BN, Peasak K, Bitzer GJ, Rader N, Weaver KL, Boehm DT, Fitzgerald N, Chapman J, Ulicny S, Damron FH, Barbier M. Virus-like particles displaying the mature C-terminal domain of filamentous hemagglutinin are immunogenic and protective against Bordetella pertussis respiratory infection in mice. Infect Immun. 2024;92(8):e0027024. doi: http://dx.doi.org/10.1128/iai.00270-24">10.1128/iai.00270-24. PubMed PMID: 39023271; PMCID: PMC11320929.
25. Kapil P, Wang Y, Zimmerman L, Gaykema M, Merkel TJ. Repeated Bordetella pertussis Infections Are Required to Reprogram Acellular Pertussis Vaccine-Primed Host Responses in the Baboon Model. J Infect Dis. 2024;229(2):376-83. doi: http://dx.doi.org/10.1093/infdis/jiad332">10.1093/infdis/jiad332. PubMed PMID: 37565807; PMCID: PMC10873172.
26. Ibsen PH. The effect of formaldehyde, hydrogen peroxide and genetic detoxification of pertussis toxin on epitope recognition by murine monoclonal antibodies. Vaccine. 1996;14(5):359-68. PubMed PMID: 8735545.
27. Hviid A, Stellfeld M, Andersen PH, Wohlfahrt J, Melbye M. Impact of routine vaccination with a pertussis toxoid vaccine in Denmark. Vaccine. 2004;22(27-28):3530-4. doi: http://dx.doi.org/10.1016/j.vaccine.2004.03.046">10.1016/j.vaccine.2004.03.046. PubMed PMID: 15315832.
28. Taranger J, Trollfors B, Bergfors E, Knutsson N, Sundh V, Lagergard T, Lind-Brandberg L, Zackrisson G, White J, Cicirello H, Fusco J, Robbins JB. Mass vaccination of children with pertussis toxoid--decreased incidence in both vaccinated and nonvaccinated persons. Clin Infect Dis. 2001;33(7):1004-10. doi: http://dx.doi.org/10.1086/322639">10.1086/322639. PubMed PMID: 11528572.
29. Thierry-Carstensen B, Dalby T, Stevner MA, Robbins JB, Schneerson R, Trollfors B. Experience with monocomponent acellular pertussis combination vaccines for infants, children, adolescents and adults--a review of safety, immunogenicity, efficacy and effectiveness studies and 15 years of field experience. Vaccine. 2013;31(45):5178-91. doi: http://dx.doi.org/10.1016/j.vaccine.2013.08.034">10.1016/j.vaccine.2013.08.034. PubMed PMID: 23994021.
30. Trollfors B, Taranger J, Lagergard T, Lind L, Sundh V, Zackrisson G, Lowe CU, Blackwelder W, Robbins JB. A placebo-controlled trial of a pertussis-toxoid vaccine. N Engl J Med. 1995;333(16):1045-50. doi: http://dx.doi.org/10.1056/NEJM199510193331604">10.1056/NEJM199510193331604. PubMed PMID: 7675047.
31. Leroux-Roels G, Lattanzi M, Solis CD, Contorni M, Costantini M, Moraschini L, Bardelli M, Bertholet S, Borgogni E, Buricchi F, Cantisani R, Faenzi E, Finco O, Leuzzi R, Pizza M, Rosa D, Schiavetti F, Seubert A, Spensieri F, Volpini G, Zedda L, Giudice GD, Galgani I. A phase I, randomized, controlled, dose-ranging study of investigational acellular pertussis (aP) and reduced tetanus-diphtheria-acellular pertussis (TdaP) booster vaccines in adults. Hum Vaccin Immunother. 2018;14(1):45-58. doi: http://dx.doi.org/10.1080/21645515.2017.1385686">10.1080/21645515.2017.1385686. PubMed PMID: 29172945; PMCID: PMC5791588.
32. Pitisuttithum P, Chokephaibulkit K, Sirivichayakul C, Sricharoenchai S, Dhitavat J, Pitisuthitham A, Phongsamart W, Boonnak K, Lapphra K, Sabmee Y, Wittawatmongkol O, Chauhan M, Wijagkanalan W, Hommalai G, Fortuna L, Chinwangso P, Poredi IK, van den Biggelaar AHJ, Pham HT, Viviani S. Antibody persistence after vaccination of adolescents with monovalent and combined acellular pertussis vaccines containing genetically inactivated pertussis toxin: a phase 2/3 randomised, controlled, non-inferiority trial. Lancet Infect Dis. 2018;18(11):1260-8. doi: http://dx.doi.org/10.1016/S1473-3099(18)30375-X">10.1016/S1473-3099(18)30375-X. PubMed PMID: 30266329.
33. Sutherland JN, Chang C, Yoder SM, Rock MT, Maynard JA. Antibodies recognizing protective pertussis toxin epitopes are preferentially elicited by natural infection versus acellular immunization. Clin Vaccine Immunol. 2011;18(6):954-62. doi: http://dx.doi.org/10.1128/CVI.00561-10">10.1128/CVI.00561-10. PubMed PMID: 21508166; PMCID: PMC3122608.
34. Carbonetti NH, Artamonova GV, Andreasen C, Bushar N. Pertussis toxin and adenylate cyclase toxin provide a one-two punch for establishment of Bordetella pertussis infection of the respiratory tract. Infect Immun. 2005;73(5):2698-703. doi: http://dx.doi.org/10.1128/IAI.73.5.2698-2703.2005">10.1128/IAI.73.5.2698-2703.2005. PubMed PMID: 15845471; PMCID: PMC1087369.
35. Goodwin MS, Weiss AA. Adenylate cyclase toxin is critical for colonization and pertussis toxin is critical for lethal infection by Bordetella pertussis in infant mice. Infect Immun. 1990;58(10):3445-7. PubMed PMID: 2401570; PMCID: PMC313675.
36. Martin C, Etxaniz A, Uribe KB, Etxebarria A, Gonzalez-Bullon D, Arlucea J, Goni FM, Arechaga J, Ostolaza H. Adenylate Cyclase Toxin promotes bacterial internalisation into non phagocytic cells. Sci Rep. 2015;5:13774. doi: http://dx.doi.org/10.1038/srep13774">10.1038/srep13774. PubMed PMID: 26346097; PMCID: PMC4642564.
37. El-Azami-El-Idrissi M, Bauche C, Loucka J, Osicka R, Sebo P, Ladant D, Leclerc C. Interaction of Bordetella pertussis adenylate cyclase with CD11b/CD18: Role of toxin acylation and identification of the main integrin interaction domain. J Biol Chem. 2003;278(40):38514-21. doi: http://dx.doi.org/10.1074/jbc.M304387200">10.1074/jbc.M304387200. PubMed PMID: 12885782.
38. Arciniega JL, Hewlett EL, Johnson FD, Deforest A, Wassilak SG, Onorato IM, Manclark CR, Burns DL. Human serologic response to envelope-associated proteins and adenylate cyclase toxin of Bordetella pertussis. J Infect Dis. 1991;163(1):135-42. doi: http://dx.doi.org/10.1093/infdis/163.1.135">10.1093/infdis/163.1.135. PubMed PMID: 1984460.
39. Cherry JD, Xing DX, Newland P, Patel K, Heininger U, Corbel MJ. Determination of serum antibody to Bordetella pertussis adenylate cyclase toxin in vaccinated and unvaccinated children and in children and adults with pertussis. Clin Infect Dis. 2004;38(4):502-7. doi: http://dx.doi.org/10.1086/381204">10.1086/381204. PubMed PMID: 14765342.
40. Farfel Z, Konen S, Wiertz E, Klapmuts R, Addy PA, Hanski E. Antibodies to Bordetella pertussis adenylate cyclase are produced in man during pertussis infection and after vaccination. J Med Microbiol. 1990;32(3):173-7. doi: http://dx.doi.org/10.1099/00222615-32-3-173">10.1099/00222615-32-3-173. PubMed PMID: 2374155.
41. Eby JC, Gray MC, Warfel JM, Merkel TJ, Hewlett EL. Use of a Toxin Neutralization Assay To Characterize the Serologic Response to Adenylate Cyclase Toxin after Infection with Bordetella pertussis. Clin Vaccine Immunol. 2017;24(1). doi: http://dx.doi.org/10.1128/CVI.00370-16">10.1128/CVI.00370-16. PubMed PMID: 27760780; PMCID: PMC5216428.
42. Guiso N, Rocancourt M, Szatanik M, Alonso JM. Bordetella adenylate cyclase is a virulence associated factor and an immunoprotective antigen. Microb Pathog. 1989;7(5):373-80. PubMed PMID: 2622329.
43. Guiso N, Szatanik M, Rocancourt M. Protective activity of Bordetella adenylate cyclase-hemolysin against bacterial colonization. Microb Pathog. 1991;11(6):423-31. PubMed PMID: 1795632.
44. Betsou F, Sebo P, Guiso N. The C-terminal domain is essential for protective activity of the Bordetella pertussis adenylate cyclase-hemolysin. Infect Immun. 1995;63(9):3309-15. PubMed PMID: 7642260; PMCID: PMC173456.
45. Wang X, Gray MC, Hewlett EL, Maynard JA. The Bordetella adenylate cyclase repeat-in-toxin (RTX) domain is immunodominant and elicits neutralizing antibodies. J Biol Chem. 2015;290(38):23025. doi: http://dx.doi.org/10.1074/jbc.A114.585281">10.1074/jbc.A114.585281. PubMed PMID: 26386047; PMCID: PMC4645631.
46. Boehm DT, Hall JM, Wong TY, DiVenere AM, Sen-Kilic E, Bevere JR, Bradford SD, Blackwood CB, Elkins CM, DeRoos KA, Gray MC, Cooper CG, Varney ME, Maynard JA, Hewlett EL, Barbier M, Damron FH. Evaluation of Adenylate Cyclase Toxoid Antigen in Acellular Pertussis Vaccines by Using a Bordetella pertussis Challenge Model in Mice. Infect Immun. 2018;86(10). doi: http://dx.doi.org/10.1128/IAI.00857-17">10.1128/IAI.00857-17. PubMed PMID: 30012638; PMCID: PMC6204743.
47. Malik AA, Imtong C, Sookrung N, Katzenmeier G, Chaicumpa W, Angsuthanasombat C. Structural Characterization of Humanized Nanobodies with Neutralizing Activity against the Bordetella pertussis CyaA-Hemolysin: Implications for a Potential Epitope of Toxin-Protective Antigen. Toxins (Basel). 2016;8(4):99. doi: http://dx.doi.org/10.3390/toxins8040099">10.3390/toxins8040099. PubMed PMID: 27043627; PMCID: PMC4848625.
48. Wang X, Stapleton JA, Klesmith JR, Hewlett EL, Whitehead TA, Maynard JA. Fine Epitope Mapping of Two Antibodies Neutralizing the Bordetella Adenylate Cyclase Toxin. Biochemistry. 2017;56(9):1324-36. doi: http://dx.doi.org/10.1021/acs.biochem.6b01163">10.1021/acs.biochem.6b01163. PubMed PMID: 28177609; PMCID: PMC5568097.
49. Mooi FR, Jansen WH, Brunings H, Gielen H, van der Heide HG, Walvoort HC, Guinee PA. Construction and analysis of Bordetella pertussis mutants defective in the production of fimbriae. Microb Pathog. 1992;12(2):127-35. PubMed PMID: 1350044.
50. Scheller EV, Melvin JA, Sheets AJ, Cotter PA. Cooperative roles for fimbria and filamentous hemagglutinin in Bordetella adherence and immune modulation. MBio. 2015;6(3):e00500-15. doi: http://dx.doi.org/10.1128/mBio.00500-15">10.1128/mBio.00500-15. PubMed PMID: 26015497; PMCID: PMC4447244.
51. Alexander F, Matheson M, Fry NK, Labram B, Gorringe AR. Antibody responses to individual Bordetella pertussis fimbrial antigen Fim2 or Fim3 following immunization with the five-component acellular pertussis vaccine or to pertussis disease. Clin Vaccine Immunol. 2012;19(11):1776-83. doi: http://dx.doi.org/10.1128/CVI.00355-12">10.1128/CVI.00355-12. PubMed PMID: 22956654; PMCID: PMC3491546.
52. Rodriguez ME, Hellwig SM, Perez Vidakovics ML, Berbers GA, van de Winkel JG. Bordetella pertussis attachment to respiratory epithelial cells can be impaired by fimbriae-specific antibodies. FEMS Immunol Med Microbiol. 2006;46(1):39-47. doi: http://dx.doi.org/10.1111/j.1574-695X.2005.00001.x">10.1111/j.1574-695X.2005.00001.x. PubMed PMID: 16420595.
53. Queenan AM, Dowling DJ, Cheng WK, Fae K, Fernandez J, Flynn PJ, Joshi S, Brightman SE, Ramirez J, Serroyen J, Wiertsema S, Fortanier A, van den Dobbelsteen G, Levy O, Poolman J. Increasing FIM2/3 antigen-content improves efficacy of Bordetella pertussis vaccines in mice in vivo without altering vaccine-induced human reactogenicity biomarkers in vitro. Vaccine. 2019;37(1):80-9. doi: http://dx.doi.org/10.1016/j.vaccine.2018.11.028">10.1016/j.vaccine.2018.11.028. PubMed PMID: 30478007.
54. Hallander HO, Ljungman M, Jahnmatz M, Storsaeter J, Nilsson L, Gustafsson L. Should fimbriae be included in pertussis vaccines? Studies on ELISA IgG anti-Fim2/3 antibodies after vaccination and infection. APMIS. 2009;117(9):660-71. doi: http://dx.doi.org/10.1111/j.1600-0463.2009.02521.x">10.1111/j.1600-0463.2009.02521.x. PubMed PMID: 19703126.
55. da Silva Antunes R, Babor M, Carpenter C, Khalil N, Cortese M, Mentzer AJ, Seumois G, Petro CD, Purcell LA, Vijayanand P, Crotty S, Pulendran B, Peters B, Sette A. Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters. J Clin Invest. 2018;128(9):3853-65. doi: http://dx.doi.org/10.1172/JCI121309">10.1172/JCI121309. PubMed PMID: 29920186; PMCID: PMC6118631.
56. Wilk MM, Borkner L, Misiak A, Curham L, Allen AC, Mills KHG. Immunization with whole cell but not acellular pertussis vaccines primes CD4 TRM cells that sustain protective immunity against nasal colonization with Bordetella pertussis. Emerg Microbes Infect. 2019;8(1):169-85. doi: http://dx.doi.org/10.1080/22221751.2018.1564630">10.1080/22221751.2018.1564630. PubMed PMID: 30866771; PMCID: PMC6455184.
57. McCarthy KN, Hone S, McLoughlin RM, Mills KHG. IL-17 and IFN-gamma-producing Respiratory Tissue-Resident Memory CD4 T Cells Persist for Decades in Adults Immunized as Children With Whole-Cell Pertussis Vaccines. J Infect Dis. 2024;230(3):e518-e23. doi: http://dx.doi.org/10.1093/infdis/jiae034">10.1093/infdis/jiae034. PubMed PMID: 38290045; PMCID: PMC11420794.
58. Christensen D, Mortensen R, Rosenkrands I, Dietrich J, Andersen P. Vaccine-induced Th17 cells are established as resident memory cells in the lung and promote local IgA responses. Mucosal Immunol. 2017;10(1):260-70. doi: http://dx.doi.org/10.1038/mi.2016.28">10.1038/mi.2016.28. PubMed PMID: 27049058.
59. Caulfield AD, Callender M, Harvill ET. Generating enhanced mucosal immunity against Bordetella pertussis: current challenges and new directions. Front Immunol. 2023;14:1126107. doi: http://dx.doi.org/10.3389/fimmu.2023.1126107">10.3389/fimmu.2023.1126107. PubMed PMID: 36895562; PMCID: PMC9990818.
60. Dubois V, Locht C. Mucosal Immunization Against Pertussis: Lessons From the Past and Perspectives. Front Immunol. 2021;12:701285. doi: http://dx.doi.org/10.3389/fimmu.2021.701285">10.3389/fimmu.2021.701285. PubMed PMID: 34211481; PMCID: PMC8239240.