NDLI: A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity

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A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity

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A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fujihashi, K. Kiyono, H. Imaoka, K. Van Ginkel, F. W. Takeda, Y. Yamamoto, M. Yamamoto, S. Noda, M. Mcghee, J. R.
Description	Author Affiliation: Yamamoto S ( Department of Microbiology, The Immunobiology Vaccine Center, University of Alabama, Medical Center, Birmingham, AL 35294-2170, USA.);
Abstract	We have characterized a nontoxic mutant of cholera toxin (CT) as a mucosal adjuvant in mice. The mutant CT was made by substitution of serine with phenylalanine at position 61 of the A subunit (S61F), which resulted in loss of ADP ribosyltransferase activity and toxicity. Mice were intranasally immunized with ovalbumin, tetanus toxoid, or influenza virus either alone or together with mutant CT S61F, native CT, or recombinant CT-B. Mice immunized with these proteins plus S61F showed high serum titers of protein-specific IgG and IgA antibodies that were comparable to those induced by native CT. Further, high protein-specific IgA antibody responses were observed in nasal and vaginal washes, saliva, and fecal extracts as well as increased numbers of IgG and IgA antibody forming cells in cervical lymph nodes and lung tissues of mice intranasally immunized with these proteins and S61F or native CT, but not with recombinant CT-B or protein alone. Both S61F and native CT enhanced the induction of ovalbumin-specific CD4(+) T cells in lung and splenic tissues, and these T cells produced a Th2-type cytokine pattern of interleukin 4 (IL-4), IL-5, IL-6, and IL-10 as determined by analysis of secreted proteins and by quantitation of cytokine-specific mRNA. These results have shown that mutant CT S61F is an effective mucosal adjuvant when administrated intranasally and induces mucosal and systemic antibody responses which are mediated by CD4(+) Th2-type cells.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	10
Volume Number	94
Language	English
Publisher	National Academy of Sciences
Publisher Date	1997-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	CD4-Positive T-Lymphocytes Immunology Cholera Toxin Cytokines Biosynthesis Intestinal Mucosa Th2 Cells Animals Antibody Formation Genetics Pharmacology Immunoglobulin A Immunoglobulin G Interferon-gamma Interleukins Lung Lymph Nodes Mice Mice, Inbred C57BL Ovalbumin Peyer's Patches Polymerase Chain Reaction RNA, Messenger Recombinant Proteins Spleen Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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