A mucosal vaccine against diphtheria: formulation of cross reacting material (CRM(197)) of diphtheria toxin with chitosan enhances local and systemic antibody and Th2 responses following nasal delivery - PubMed

A mucosal vaccine against diphtheria: formulation of cross reacting material (CRM(197)) of diphtheria toxin with chitosan enhances local and systemic antibody and Th2 responses following nasal delivery

E A McNeela et al. Vaccine. 2000.

Abstract

The development of new generation vaccines against diphtheria is dependent on the identification of antigens and routes of immunization that are capable of stimulating immune responses similar to, or greater than, those obtained with the parenterally-delivered toxoid vaccine, while reducing the adverse effects that have been associated with the traditional vaccine. In this study, we examined the cellular and humoral immune responses in mice generated after both parenteral and mucosal immunizations with cross-reacting material (CRM(197)) of diphtheria toxin. We found that both native and mildly formaldehyde-treated CRM(197) and conventional diphtheria toxoid (DT) induced mixed Th1/Th2 responses and similar levels of anti-DT serum IgG following parenteral immunization. In contrast, CRM(197) preparations were poorly immunogenic when administered intranasally in solution. However, formulation of the antigens with chitosan significantly enhanced their immunogenicity, inducing high levels of antigen-specific IgG, secretory IgA, toxin-neutralizing antibodies and T cell responses, predominately of Th2 subtype. Furthermore, intranasal immunization with CRM(197) and chitosan induced protective antibodies against the toxin in a guinea pig passive challenge model. We also found that priming parenterally with DT in alum and boosting intranasally with CRM(197) was a very effective method of immunization in mice, capable of inducing high levels of anti-DT IgG and neutralizing antibodies in the serum and secretory IgA in the respiratory tract. Our findings suggest that boosting intranasally with CRM(197) antigen may be very effective in adolescents or adults who have previously been parenterally immunized with a conventional diphtheria toxoid vaccine.

Similar articles

• Intranasal immunization with genetically detoxified diphtheria toxin induces T cell responses in humans: enhancement of Th2 responses and toxin-neutralizing antibodies by formulation with chitosan.

  McNeela EA, Jabbal-Gill I, Illum L, Pizza M, Rappuoli R, Podda A, Lewis DJ, Mills KH. McNeela EA, et al. Vaccine. 2004 Feb 25;22(8):909-14. doi: 10.1016/j.vaccine.2003.09.012. Vaccine. 2004. PMID: 15161067 Clinical Trial.

• Protective levels of diphtheria-neutralizing antibody induced in healthy volunteers by unilateral priming-boosting intranasal immunization associated with restricted ipsilateral mucosal secretory immunoglobulin a.

  Mills KH, Cosgrove C, McNeela EA, Sexton A, Giemza R, Jabbal-Gill I, Church A, Lin W, Illum L, Podda A, Rappuoli R, Pizza M, Griffin GE, Lewis DJ. Mills KH, et al. Infect Immun. 2003 Feb;71(2):726-32. doi: 10.1128/IAI.71.2.726-732.2003. Infect Immun. 2003. PMID: 12540551 Free PMC article.

• Transcutaneous immunization with cross-reacting material CRM(197) of diphtheria toxin boosts functional antibody levels in mice primed parenterally with adsorbed diphtheria toxoid vaccine.

  Stickings P, Peyre M, Coombes L, Muller S, Rappuoli R, Del Giudice G, Partidos CD, Sesardic D. Stickings P, et al. Infect Immun. 2008 Apr;76(4):1766-73. doi: 10.1128/IAI.00797-07. Epub 2008 Jan 28. Infect Immun. 2008. PMID: 18227167 Free PMC article.

• Chitosan as a novel nasal delivery system for vaccines.

  Illum L, Jabbal-Gill I, Hinchcliffe M, Fisher AN, Davis SS. Illum L, et al. Adv Drug Deliv Rev. 2001 Sep 23;51(1-3):81-96. doi: 10.1016/s0169-409x(01)00171-5. Adv Drug Deliv Rev. 2001. PMID: 11516781 Review.

• Effect of immunity to the carrier protein on antibody responses to Haemophilus influenzae type b conjugate vaccines.

  Granoff DM, Rathore MH, Holmes SJ, Granoff PD, Lucas AH. Granoff DM, et al. Vaccine. 1993;11 Suppl 1:S46-51. doi: 10.1016/0264-410x(93)90160-y. Vaccine. 1993. PMID: 8447176 Review.

Cited by

• Preparation and efficacy of Newcastle disease virus DNA vaccine encapsulated in chitosan nanoparticles.

  Zhao K, Zhang Y, Zhang X, Li W, Shi C, Guo C, Dai C, Chen Q, Jin Z, Zhao Y, Cui H, Wang Y. Zhao K, et al. Int J Nanomedicine. 2014;9:389-402. doi: 10.2147/IJN.S54226. Epub 2014 Jan 7. Int J Nanomedicine. 2014. PMID: 24426783 Free PMC article.

• Intranasal immunization with chitosan/pCAGGS-flaA nanoparticles inhibits Campylobacter jejuni in a White Leghorn model.

  Huang JL, Yin YX, Pan ZM, Zhang G, Zhu AP, Liu XF, Jiao XA. Huang JL, et al. J Biomed Biotechnol. 2010;2010:589476. doi: 10.1155/2010/589476. Epub 2010 Aug 16. J Biomed Biotechnol. 2010. PMID: 20936115 Free PMC article.

• Absorption enhancers for nasal drug delivery.

  Davis SS, Illum L. Davis SS, et al. Clin Pharmacokinet. 2003;42(13):1107-28. doi: 10.2165/00003088-200342130-00003. Clin Pharmacokinet. 2003. PMID: 14531723 Review.

• SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants.

  Martínez-Flores D, Zepeda-Cervantes J, Cruz-Reséndiz A, Aguirre-Sampieri S, Sampieri A, Vaca L. Martínez-Flores D, et al. Front Immunol. 2021 Jul 12;12:701501. doi: 10.3389/fimmu.2021.701501. eCollection 2021. Front Immunol. 2021. PMID: 34322129 Free PMC article. Review.

• Intranasal immunization with dry powder vaccines.

  Bahamondez-Canas TF, Cui Z. Bahamondez-Canas TF, et al. Eur J Pharm Biopharm. 2018 Jan;122:167-175. doi: 10.1016/j.ejpb.2017.11.001. Epub 2017 Nov 6. Eur J Pharm Biopharm. 2018. PMID: 29122735 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Miscellaneous

  • NCI CPTAC Assay Portal