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    Vaccination with HPV16 L2E6E7 fusion protein in GPI-0100 adjuvant elicits protective humoral and cell-mediated immunity.

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    Authors
    Karanam, Balasubramanyam
    Gambhira, Ratish
    Peng, Shiwen
    Jagu, Subhashini
    Kim, Dae-Jin
    Ketner, Gary W
    Stern, Peter L
    Adams, Robert J
    Roden, Richard B S
    Affiliation
    Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231, USA.
    Issue Date
    2009-02-11
    
    Metadata
    Show full item record
    Abstract
    A vaccine comprising human papillomavirus type 16 (HPV16) L2, E6 and E7 in a single tandem fusion protein (termed TA-CIN) has the potential advantages of both broad cross-protection against HPV transmission through induction of L2 antibodies able to cross neutralize different HPV types and of therapy by stimulating T cell responses targeting HPV16 early proteins. However, patients vaccinated with TA-CIN alone develop weak HPV neutralizing antibody and E6/E7-specific T cell responses. Here we test TA-CIN formulated along with the adjuvant GPI-0100, a semi-synthetic quillaja saponin analog that was developed to promote both humoral and cellular immune responses. Subcutaneous administration to mice of TA-CIN (20 microg) with 50microg GPI-0100, three times at biweekly intervals, elicited high titer HPV16 neutralizing serum antibody, robust neutralizing titers for other HPV16-related types, including HPV31 and HPV58, and neutralized to a lesser extent other genital mucosatropic papillomaviruses like HPV18, HPV45, HPV6 and HPV11. Notably, vaccination with TA-CIN in GPI-0100 protected mice from cutaneous HPV16 challenge as effectively as HPV16 L1 VLP without adjuvant. Formulation of TA-CIN with GPI-0100 enhanced the production of E7-specific, interferon gamma producing CD8(+) T cell precursors by 20-fold. Vaccination with TA-CIN in GPI-0100 also completely prevented tumor growth after challenge with 5x10(4) HPV16-transformed TC-1 tumor cells, whereas vaccination with TA-CIN alone delayed tumor growth. Furthermore, three monthly vaccinations with 125 microg of TA-CIN and 1000 microg GPI-0100 were well tolerated by pigtail macaques and induced both HPV16 E6/E7-specific T cell responses and serum antibodies that neutralized all HPV types tested.
    Citation
    Vaccination with HPV16 L2E6E7 fusion protein in GPI-0100 adjuvant elicits protective humoral and cell-mediated immunity. 2009, 27 (7):1040-9 Vaccine
    Journal
    Vaccine
    URI
    http://hdl.handle.net/10541/69793
    DOI
    10.1016/j.vaccine.2008.11.099
    PubMed ID
    19095032
    Type
    Article
    Language
    en
    ISSN
    0264-410X
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.vaccine.2008.11.099
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research
    Immunology

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