Mucosal immunogenicity of genetically detoxified derivatives of heat labile toxin from Escherichia coli.

Abstract:

:Using a fixed dose of antigen, the immune response to detoxified mutants of LT-WT following intranasal (i.n.), subcutaneous (s.c.) and oral (i.g.) immunisation has been studied. When given i.n., both LT-WT and mutant toxin, K63, generated significant levels of toxin-specific IgG in the serum, and the levels of IgA in nasal and lung lavages were greater than those induced by rLT-B. In comparison, i.g. immunisation of mice with a similar quantity of either LT-WT or K63 toxin induced barely detectable levels of IgG in the sera. However, if the amount of protein used for i.g. immunisation was increased tenfold, relatively good levels of toxin-specific IgG were induced in the sera by both LT-WT or K63. Low levels of toxin-specific IgA were also observed in intestinal washes from these mice. Western blotting of the sera, using the native toxin as an antigen, demonstrated the presence of both anti-A and anti-B subunit antibodies. Most significantly, toxin-neutralising antibodies were induced in the serum, with the strongest activity being induced by the LT-WT, an intermediate activity induced by mutant K63 and a lower response by rLT-B. Together, these data show that ADP-ribosyltransferase is not necessary for mucosal immunogenicity of these proteins, and that the i.n. route of immunisation is more effective than the i.g. route of immunisation for the generation of both systemic (IgG) and mucosal (IgA) immune responses.

journal_name

Vaccine

journal_title

Vaccine

authors

Douce G,Giuliani MM,Giannelli V,Pizza MG,Rappuoli R,Dougan G

doi

10.1016/s0264-410x(98)80100-x

subject

Has Abstract

pub_date

1998-07-01 00:00:00

pages

1065-73

issue

11-12

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(98)80100-X

journal_volume

16

pub_type

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