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Antibodies to keyhole limpet hemocyanin cross-react with an epitope on the polysaccharide capsule of Cryptococcus neoformans and other carbohydrates: implications for vaccine development.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 Nov 01; Vol. 171 (9), pp. 4905-12. - Publication Year :
- 2003
-
Abstract
- Cryptococcus neoformans causes a life-threatening meningoencephalitis in AIDS patients. Mice immunized with a glycoconjugate vaccine composed of the glucuronoxylomannan (GXM) component of the cryptococcal capsular polysaccharide conjugated to tetanus toxoid produce Abs that can be either protective or nonprotective. Because nonprotective Abs block the efficacy of protective Abs, an effective vaccine must focus the Ab response on a protective epitope. Mice immunized with peptide mimetics of GXM conjugated to keyhole limpet hemocyanin (KLH) with glutaraldehyde developed Abs to GXM. However, control peptides P315 and P24 conjugated to KLH also elicited Abs to GXM. GXM-binding Abs from mice immunized with P315-KLH were inhibited by KLH treated with glutaraldehyde (KLH-g), but not by P315. Furthermore, KLH-g inhibited binding of GXM by serum of mice immunized with GXM-TT, indicating that glutaraldehyde treatment of KLH reveals an epitope(s) that cross-reacts with GXM. Vaccination with KLH-g or unmodified KLH elicited Abs to GXM, but did not confer protection against C. neoformans, suggesting the cross-reactive epitope on KLH was not protective. This was supported by the finding that 4H3, a nonprotective mAb, cross-reacted strongly with KLH-g. Sera from mice immunized with either native KLH or KLH-g cross-reacted with several other carbohydrate Ags, many of which have been conjugated to KLH for vaccine development. This study illustrates how mAbs can be used to determine the efficacy of potential vaccines, in addition to describing the complexity of using KLH and glutaraldehyde in the development of vaccines to carbohydrate Ags.
- Subjects :
- Amino Acid Sequence
Animals
Antibodies, Fungal metabolism
Antigens, Fungal metabolism
Antigens, Fungal therapeutic use
Cross Reactions
Fungal Vaccines metabolism
Fungal Vaccines therapeutic use
Glutaral pharmacology
Immunodominant Epitopes metabolism
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Polysaccharides metabolism
Vaccines, Subunit immunology
Vaccines, Subunit metabolism
Vaccines, Subunit therapeutic use
Antibodies metabolism
Antigens, Fungal immunology
Cryptococcus neoformans immunology
Epitopes metabolism
Fungal Vaccines immunology
Hemocyanins immunology
Polysaccharides immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 171
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 14568972
- Full Text :
- https://doi.org/10.4049/jimmunol.171.9.4905