Journal
VACCINE
Volume 20, Issue 5-6, Pages 756-762Publisher
ELSEVIER SCI LTD
DOI: 10.1016/S0264-410X(01)00412-1
Keywords
cholera toxin; diphtheria toxin; mucosal adjuvant; mucosal immunity; mutant toxin
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Funding
- NIAID NIH HHS [AI 65299, AI 43197, AI 35932, AI 18958] Funding Source: Medline
- NIDCD NIH HHS [DC 04976] Funding Source: Medline
- NIDCR NIH HHS [DE 09837] Funding Source: Medline
- NIDDK NIH HHS [DK 44042, P30 DK 54781] Funding Source: Medline
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We demonstrated that the mutant of cholera toxin (mCT) E112K which, was LPS-free supported the induction of protective immunity in mucosal (e.g. lung lavage) and systemic (e.g. serum) compartments when given nasally with vaccine-grade diphtheria toxoid (DT) to mice. Significant DT-specific mucosal IgA antibody (Ab) and serum IgG, IgA and IgM Ab responses were induced when LPS-depleted mCT E112K. or native CT (nCT) was co-administered nasally with DT. The analysis of DT-specific Ab-forming cell (AFC) responses supported the Ab titers and significant numbers of DT-specific IgA AFC were present in the lungs, nasal passages and submandibular glands. Furthermore, DT-specific IgG AFC in cervical lymph nodes (CLN) and the spleen were induced in mice administered with DT nasally with either mCT or nCT. The analysis of antigen-specific T cell responses revealed that increased DT-specific CD4(+) T cell proliferative and Th2-type cytokine responses were induced in mice nasally-immunized with DT and the LPS-free form of mCT. The neutralization of diphtheria toxin by Abs showed that DT-specific IgG Ab responses in serum and lung lavages of mice immunized with DT and mCT were protective. Furthermore, it was shown that an IgA-enriched fraction of lung lavages possessed diphtheria toxin-specific neutralizing activity. These results are the first demonstration that nasally co-administered mCT E112K can induce DT-specific protective Ab responses in mucosal compartments (e.g. lung lavages and the lungs). (C) 2001 Elsevier Science Ltd. All rights reserved.
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