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    Seroepidemiology of Human Papillomavirus 16 (HPV16) L2 and Generation of L2-Specific Human Chimeric Monoclonal Antibodies.

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    Authors
    Wang, J
    Jagu, S
    Wu, W
    Viscidi, R
    Macgregor-Das, A
    Fogel, J
    Kwak, K
    Daayana, S
    Kitchener, H
    Stern, Peter L
    Gravitt, P
    Trimble, C
    Roden, R
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    Affiliation
    Departments of Pathology, The Johns Hopkins University, Baltimore, MD, USA
    Issue Date
    2015-07
    
    Metadata
    Show full item record
    Abstract
    Presently, the seroprevalence of human papillomavirus (HPV) minor capsid antigen L2-reactive antibody is not well understood, and no serologic standard exists for L2-specific neutralizing antibodies. Therefore, we screened a total of 1,078 serum samples for HPV16 L2 reactivity, and these were obtained from four prior clinical studies: a population-based (n = 880) surveillance study with a high-risk HPV DNA prevalence of 10.8%, a cohort study of women (n = 160) with high-grade cervical intraepithelial neoplasia (CIN), and two phase II trials in women with high-grade vulvar intraepithelial neoplasia (VIN) receiving imiquimod therapy combined with either photodynamic therapy (PDT) (n = 19) or vaccination with a fusion protein comprising HPV16 L2, E7, and E6 (TA-CIN) (n = 19). Sera were screened sequentially by HPV16 L2 enzyme-linked immunosorbent assay (ELISA) and then Western blot. Seven of the 1,078 serum samples tested had L2-specific antibodies, but none were detectably neutralizing for HPV16. To develop a standard, we substituted human IgG1 sequences into conserved regions of two rodent monoclonal antibodies (MAbs) specific for neutralizing epitopes at HPV16 L2 residues 17 to 36 and 58 to 64, creating JWW-1 and JWW-2, respectively. These chimeric MAbs retained neutralizing activity and together reacted with 33/34 clinically relevant HPV types tested. In conclusion, our inability to identify an HPV16 L2-specific neutralizing antibody response even in the sera of patients with active genital HPV disease suggests the subdominance of L2 protective epitopes and the value of the chimeric MAbs JWW-1 and JWW-2 as standards for immunoassays to measure L2-specific human antibodies.
    Citation
    Seroepidemiology of Human Papillomavirus 16 (HPV16) L2 and Generation of L2-Specific Human Chimeric Monoclonal Antibodies. 2015, 22 (7):806-16 Clin Vaccine Immunol
    Journal
    Clinical and Vaccine Immunology
    URI
    http://hdl.handle.net/10541/559301
    DOI
    10.1128/CVI.00799-14
    PubMed ID
    25972404
    Type
    Article
    Language
    en
    ISSN
    1556-679X
    ae974a485f413a2113503eed53cd6c53
    10.1128/CVI.00799-14
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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