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Characterization of the Antibody Response to Two Distinct Neutralizing Epitopes on Human Papilloma virus Type 6 Virus‐Like Particle
Author(s) -
Matys Katie,
Opalka David,
Brown Martha,
Smith Judith,
Brownlow Michelle,
Green Tina,
Sikkema Daniel,
Bryan Janine,
Esser Mark Thomas,
Bryna Janine
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.861.5
Subject(s) - epitope , virology , avidity , antibody , monoclonal antibody , neutralizing antibody , biology , virus like particle , virus , immunology , recombinant dna , gene , biochemistry
Human papillomaviruses (HPV) infect epithelial cells, including the epithelium of mucous membranes. GARDASIL™ was approved for the prevention of genital warts, vaginal, vulvar and cervical cancer caused by HPV types 6, 11, 16 and 18. A competitive Luminex immunoassay (cLIA) has been developed to measure serum levels of virus‐like particle (VLP) type‐specific antibodies. The cLIA uses neutralizing, type‐specific, R‐phycoerythrin‐labeled monoclonal antibodies to monitor the antibody response to type‐specific, neutralizing epitopes on the VLPs. Antibody responses to two distinct neutralizing epitopes on VLP‐6 were characterized using monoclonal antibodies H6.M48 and H6.1C2. Both the H6.M48 and H6.1C2 mAbs bind to HPV‐6 VLPs. Competition assays showed that the H6.M48 and H6.1C2 bind to type‐specific, overlapping, neutralizing epitopes. Avidity analysis shows that the H6.1C2 binds to the HPV 6 VLP with greater avidity than the H6.M48 mAb. Sera from individuals with confirmed HPV‐6 infection, a history of genital warts or sera from females who had been vaccinated with GARDASIL were tested in competition experiments with both of the mAbs. Results show that the H6.1C2 mAb binds to a more immunodominant epitope than the H6.M48 mAb as recognized by serum antibodies from both vaccinees and naturally infected individuals as indicated by a high prevalence in such antibodies in sera collected.

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