Browsing by Author "Patricia Fitton"

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    Cross-reacting antibodies enhance dengue virus infection in humans
    (2010-05-07) Wanwisa Dejnirattisai; Amonrat Jumnainsong; Naruthai Onsirisakul; Patricia Fitton; Sirijitt Vasanawathana; Wannee Limpitikul; Chunya Puttikhunt; Carolyn Edwards; Thaneeya Duangchinda; Sunpetchuda Supasa; Kriangkrai Chawansuntati; Prida Malasit; Juthathip Mongkolsapaya; Gavin Screaton; Imperial College London; Mahidol University; Khon Kaen Regional Hospital; Songkhla Hospital; Thailand National Center for Genetic Engineering and Biotechnology
    Dengue virus co-circulates as four serotypes, and sequential infections with more than one serotype are common. One hypothesis for the increased severity seen in secondary infections is antibodydependent enhancement (ADE) leading to increased replication in Fc receptor-bearing cells. In this study, we have generated a panel of human monoclonal antibodies to dengue virus. Antibodies to the structural precursor-membrane protein (prM) form a major component of the response. These antibodies are highly cross-reactive among the dengue virus serotypes and, even at high concentrations, do not neutralize infection but potently promote ADE. We propose that the partial cleavage of prM from the viral surface reduces the density of antigen available for viral neutralization, leaving dengue viruses susceptible to ADE by antibody to prM, a finding that has implications for future vaccine design.