{"id":{"repo_id":"washington","oai_identifier":"oai:digital.lib.washington.edu:1773/21740"},"canonical_url":"https://search.dev.ndltd.org/etd/washington/oai:digital.lib.washington.edu:1773/21740","repository":{"repo_id":"washington","name":"University of Washington","base_url":"https://digital.lib.washington.edu/server/oai/request"},"display":{"title":"Development and Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1","abstract":"A neutralizing antibody response of sufficient potency, magnitude and duration is considered an important part of a successful HIV vaccine. A better understanding of the factors associated with the development of broadly neutralizing antibody responses (effective against a wide range of clinical isolates), and the epitopes they target, will aid in our understanding of how to elicit such responses by vaccination. Cross-sectional studies of chronic HIV-1 infection have demonstrated that approximately 15% of HIV-1-infected subjects develop such responses. We characterized the development and epitope specificities of the earliest serum cross-reactive neutralizing antibody responses in an acute/early HIV infection cohort. We demonstrate that 29% of subjects in that cohort develop such responses within 2-3 years of infection. Our epitope-mapping results indicate that the earliest cross-neutralizing antibody responses target a limited number of regions on the HIV Envelope, often involving the highly conserved CD4-binding site on the HIV Envelope. In a case study of an HIV-1-infected individual we aimed to understand the emergence and evolution of the earliest cross-neutralizing antibody responses, and identified two distinct epitope specificities. Antibodies that targeted the CD4-BS became detectable at around 3 years post infection, and were responsible for the neutralization of most cross-clade viral isolates tested. Another specificity became apparent over a year later, which was due to broadly neutralizing antibodies specific to a carbohydrate at position 160 on the HIV Env. Our findings supports vaccine design efforts that aim to elicit multiple antibody specificities.","abstract_html":"A neutralizing antibody response of sufficient potency, magnitude and duration is considered an important part of a successful HIV vaccine. A better understanding of the factors associated with the development of broadly neutralizing antibody responses (effective against a wide range of clinical isolates), and the epitopes they target, will aid in our understanding of how to elicit such responses by vaccination. Cross-sectional studies of chronic HIV-1 infection have demonstrated that approximately 15% of HIV-1-infected subjects develop such responses. We characterized the development and epitope specificities of the earliest serum cross-reactive neutralizing antibody responses in an acute/early HIV infection cohort. We demonstrate that 29% of subjects in that cohort develop such responses within 2-3 years of infection. Our epitope-mapping results indicate that the earliest cross-neutralizing antibody responses target a limited number of regions on the HIV Envelope, often involving the highly conserved CD4-binding site on the HIV Envelope. In a case study of an HIV-1-infected individual we aimed to understand the emergence and evolution of the earliest cross-neutralizing antibody responses, and identified two distinct epitope specificities. Antibodies that targeted the CD4-BS became detectable at around 3 years post infection, and were responsible for the neutralization of most cross-clade viral isolates tested. Another specificity became apparent over a year later, which was due to broadly neutralizing antibodies specific to a carbohydrate at position 160 on the HIV Env. 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A better understanding of the factors associated with the development of broadly neutralizing antibody responses (effective against a wide range of clinical isolates), and the epitopes they target, will aid in our understanding of how to elicit such responses by vaccination. Cross-sectional studies of chronic HIV-1 infection have demonstrated that approximately 15% of HIV-1-infected subjects develop such responses. We characterized the development and epitope specificities of the earliest serum cross-reactive neutralizing antibody responses in an acute/early HIV infection cohort. We demonstrate that 29% of subjects in that cohort develop such responses within 2-3 years of infection. Our epitope-mapping results indicate that the earliest cross-neutralizing antibody responses target a limited number of regions on the HIV Envelope, often involving the highly conserved CD4-binding site on the HIV Envelope. In a case study of an HIV-1-infected individual we aimed to understand the emergence and evolution of the earliest cross-neutralizing antibody responses, and identified two distinct epitope specificities. Antibodies that targeted the CD4-BS became detectable at around 3 years post infection, and were responsible for the neutralization of most cross-clade viral isolates tested. Another specificity became apparent over a year later, which was due to broadly neutralizing antibodies specific to a carbohydrate at position 160 on the HIV Env. Our findings supports vaccine design efforts that aim to elicit multiple antibody specificities."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Development and Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1"]}]}],"canonical_facts":{"dc:contributor.advisor":["Stamatatos, Leonidas"],"dc:creator":["Mikell, Iliyana"],"dc:date.accessioned":["2013-02-25T17:49:06Z"],"dc:date.available":["2015-12-14T17:55:55Z"],"dc:date.issued":["2013-02-25"],"dc:description":["Thesis (Ph.D.)--University of Washington, 2012"],"dc:description.abstract":["A neutralizing antibody response of sufficient potency, magnitude and duration is considered an important part of a successful HIV vaccine. A better understanding of the factors associated with the development of broadly neutralizing antibody responses (effective against a wide range of clinical isolates), and the epitopes they target, will aid in our understanding of how to elicit such responses by vaccination. Cross-sectional studies of chronic HIV-1 infection have demonstrated that approximately 15% of HIV-1-infected subjects develop such responses. We characterized the development and epitope specificities of the earliest serum cross-reactive neutralizing antibody responses in an acute/early HIV infection cohort. We demonstrate that 29% of subjects in that cohort develop such responses within 2-3 years of infection. Our epitope-mapping results indicate that the earliest cross-neutralizing antibody responses target a limited number of regions on the HIV Envelope, often involving the highly conserved CD4-binding site on the HIV Envelope. In a case study of an HIV-1-infected individual we aimed to understand the emergence and evolution of the earliest cross-neutralizing antibody responses, and identified two distinct epitope specificities. Antibodies that targeted the CD4-BS became detectable at around 3 years post infection, and were responsible for the neutralization of most cross-clade viral isolates tested. Another specificity became apparent over a year later, which was due to broadly neutralizing antibodies specific to a carbohydrate at position 160 on the HIV Env. Our findings supports vaccine design efforts that aim to elicit multiple antibody specificities."],"dc:format.mimetype":["application/pdf"],"dc:identifier.other":["Mikell_washington_0250E_10926.pdf"],"dc:identifier.uri":["http://hdl.handle.net/1773/21740"],"dc:language.iso":["en_US"],"dc:rights":["Copyright is held by the individual authors."],"dc:title":["Development and Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T05:58:16Z"}