TY - JOUR
T1 - Reactivity pattern of 92 monoclonal antibodies with 15 human papillomavirus types
AU - Rizk, Raeda Z.
AU - Christensen, Neil D.
AU - Michael, Kristina M.
AU - Müller, Martin
AU - Sehr, Peter
AU - Waterboer, Tim
AU - Pawlita, Michael
PY - 2008/1
Y1 - 2008/1
N2 - Most anti-human papillomavirus (HPV) capsid antibody assays are based on virus-like particles (VLP). We evaluated glutathione S-transferase (GST)-L1 fusion proteins as ELISA antigens for determining type specificity and cross-reactivity of 92 VLP-specific monoclonal antibodies (mAb) generated against nine mucosal alpha papillomavirus types of species 7, 9 and 10. The antibody panel included 25 new mAb, and 24 previously published mAb are further characterized. We determined the cross-reactivity patterns with 15 different HPV types representing 6 species (alpha1, 2, 4, 7, 9 and 10) and neutralization and cross-neutralization properties with HPV types 6, 11, 16, 18 and 45. Eighty-nine (97%) of the antibodies including 34, 71 and 14 recognizing neutralizing, conformational and linear epitopes, respectively, reacted with the GST-L1 protein of the HPV type used as immunogen, with log titres ranging from 2.0 to 7.3. Of these 89 antibodies, 52% were monotypic, 20% showed intra-species and 28% inter-species cross-reactivity. Log neutralization titres to the immunogen HPV ranged from 1.7 to 5.6. A single cross-neutralizing mAb (H6.L12) was found. ELISA titres were always higher than neutralization titres. All neutralizing epitopes were conformational and mostly type-specific. Our data show that bacterially expressed, affinity-purified GST-L1 fusion proteins display a broad variety of epitopes and thus are well suited for detection of HPV antibodies. Cross-reactivity is associated with linear as well as conformational epitopes. Distantly related mucosal and skin alpha papillomaviruses share some conformational epitopes and the phylogenetic L1-based species definition may not define a serological unit since no species-specific epitope was found.
AB - Most anti-human papillomavirus (HPV) capsid antibody assays are based on virus-like particles (VLP). We evaluated glutathione S-transferase (GST)-L1 fusion proteins as ELISA antigens for determining type specificity and cross-reactivity of 92 VLP-specific monoclonal antibodies (mAb) generated against nine mucosal alpha papillomavirus types of species 7, 9 and 10. The antibody panel included 25 new mAb, and 24 previously published mAb are further characterized. We determined the cross-reactivity patterns with 15 different HPV types representing 6 species (alpha1, 2, 4, 7, 9 and 10) and neutralization and cross-neutralization properties with HPV types 6, 11, 16, 18 and 45. Eighty-nine (97%) of the antibodies including 34, 71 and 14 recognizing neutralizing, conformational and linear epitopes, respectively, reacted with the GST-L1 protein of the HPV type used as immunogen, with log titres ranging from 2.0 to 7.3. Of these 89 antibodies, 52% were monotypic, 20% showed intra-species and 28% inter-species cross-reactivity. Log neutralization titres to the immunogen HPV ranged from 1.7 to 5.6. A single cross-neutralizing mAb (H6.L12) was found. ELISA titres were always higher than neutralization titres. All neutralizing epitopes were conformational and mostly type-specific. Our data show that bacterially expressed, affinity-purified GST-L1 fusion proteins display a broad variety of epitopes and thus are well suited for detection of HPV antibodies. Cross-reactivity is associated with linear as well as conformational epitopes. Distantly related mucosal and skin alpha papillomaviruses share some conformational epitopes and the phylogenetic L1-based species definition may not define a serological unit since no species-specific epitope was found.
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U2 - 10.1099/vir.0.83145-0
DO - 10.1099/vir.0.83145-0
M3 - Article
C2 - 18089735
AN - SCOPUS:38349049459
VL - 89
SP - 117
EP - 129
JO - Journal of General Virology
JF - Journal of General Virology
SN - 0022-1317
IS - 1
ER -