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Eliciting a neutralizing-antibody response is a goal of many vaccine development programs and commonly correlates with protection from disease. Considerable insights into the mechanisms of neutralization have been gained from studies of monoclonal antibodies, yet the individual contributions and dynamics of the repertoire of circulating antibody specificities elicited by infection and vaccination are poorly understood on the functional and molecular levels. Neutralizing antibodies with the most protective functionalities may be a rare component of a polyclonal, pathogen-specific antibody response, further complicating efforts to identify the elements of a protective immune response. This review discusses advances in deconstructing polyclonal antibody responses to flavivirus infection or vaccination. Our discussions draw comparisons to HIV-1, a virus with a distinct structure and replication cycle for which the antibody response has been extensively investigated. Progress toward deconstructing and understanding the components of polyclonal antibody responses identifies new targets and challenges for vaccination strategies.<\/jats:p>","DOI":"10.1128\/mmbr.00024-15","type":"journal-article","created":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T01:59:47Z","timestamp":1477533587000},"page":"989-1010","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":111,"title":["Deconstructing the Antiviral Neutralizing-Antibody Response: Implications for Vaccine Development and Immunity"],"prefix":"10.1128","volume":"80","author":[{"given":"Laura A.","family":"VanBlargan","sequence":"first","affiliation":[{"name":"Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Goo","sequence":"additional","affiliation":[{"name":"Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore C.","family":"Pierson","sequence":"additional","affiliation":[{"name":"Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.09.046"},{"key":"e_1_3_2_3_2","first-page":"109","article-title":"A model for neutralization of viruses based on antibody coating of the virion surface","volume":"260","author":"Burton DR","year":"2001","unstructured":"Burton DR, Saphire EO, Parren PW. 2001. 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