In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection

Alwis, Ruklanthi de; Beltramello, Martina; Messer, William B.; Sukupolvi-Petty, Soila; Wahala, Wahala M. P. B.; Kraus, Annette; Olivarez, Nicholas P.; Pham, Quang; Brian, James; Tsai, Wen-Yang; Wang, Wei-Kung; Halstead, Scott; Kliks, Srisakul; Diamond, Michael S.; Baric, Ralph; Lanzavecchia, Antonio; Sallusto, Federica; Silva, Aravinda M. de

doi:10.1371/journal.pntd.0001188

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Journal article

In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection

Alwis, Ruklanthi de Department of Microbiology and Immunology, and the Southeast Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America
Beltramello, Martina Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Messer, William B. Department of Microbiology and Immunology, and the Southeast Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America
Sukupolvi-Petty, Soila Departments of Medicine, Molecular Microbiology, Pathology and Immunology, and the Midwest Regional Center for Biodefense and Emerging Infectious Diseases Research, Washington University School of Medicine, St. Louis, Missouri, United States of America
Wahala, Wahala M. P. B. Department of Microbiology and Immunology, and the Southeast Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America
Kraus, Annette Department of Microbiology and Immunology, and the Southeast Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America
Olivarez, Nicholas P. Department of Microbiology and Immunology, and the Southeast Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America
Pham, Quang Department of Microbiology and Immunology, and the Southeast Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America
Brian, James Departments of Medicine, Molecular Microbiology, Pathology and Immunology, and the Midwest Regional Center for Biodefense and Emerging Infectious Diseases Research, Washington University School of Medicine, St. Louis, Missouri, United States of America
Tsai, Wen-Yang Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, United States of America
Wang, Wei-Kung Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, United States of America
Halstead, Scott Pediatric Dengue Vaccine Initiative, International Vaccine Institute, Seoul, Korea
Kliks, Srisakul Pediatric Dengue Vaccine Initiative, International Vaccine Institute, Seoul, Korea
Diamond, Michael S. Departments of Medicine, Molecular Microbiology, Pathology and Immunology, and the Midwest Regional Center for Biodefense and Emerging Infectious Diseases Research, Washington University School of Medicine, St. Louis, Missouri, United States of America
Baric, Ralph Department of Microbiology and Immunology, and the Southeast Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Silva, Aravinda M. de Department of Microbiology and Immunology, and the Southeast Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America

21.06.2011

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Plos neglected tropical diseases. - 2011, vol. 5, no. 6, p. e1188

English Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization.

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