Clinical validation of the "in silico" prediction of immunogenicity of a human recombinant therapeutic protein.
Clin Immunol
; 124(1): 26-32, 2007 Jul.
Article
em En
| MEDLINE
| ID: mdl-17490912
ABSTRACT
Antibodies elicited by protein therapeutics can cause serious side effects in humans. We studied immunogenicity of a recombinant fusion protein (FPX) consisting of two identical, biologically active, peptides attached to human Fc fragment. EpiMatrix, an in silico epitope-mapping tool, predicted promiscuous T-cell epitope(s) within the 14-amino-acid carboxy-terminal region of the peptide portion of FPX. On administration of FPX in 76 healthy human subjects, 37% developed antibodies after a single injection. A memory T-cell response against the above carboxy-terminus of the peptide was observed in antibody-positive but not in antibody-negative subjects. Promiscuity of the predicted T-cell epitope(s) was confirmed by representation of all common HLA alleles in antibody-positive subjects. As predicted by EpiMatrix, HLA haplotype DRB1*0701/1501 was associated with the highest T-cell and antibody response. In conclusion, in silico prediction can be successfully used to identify Class II restricted T-cell epitopes within therapeutic proteins and predict immunogenicity thereof in humans.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Simulação por Computador
/
Proteínas Recombinantes de Fusão
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Epitopos Imunodominantes
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Modelos Imunológicos
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Epitopos de Linfócito T
/
Biologia Computacional
Tipo de estudo:
Evaluation_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article