Journal
IMMUNITY
Volume 49, Issue 2, Pages 288-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2018.07.009
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Funding
- NIH [UM1 AI100663]
- Bill and Melinda Gates Foundation [OPP1115782, OPP1084519]
- Swiss National Science Foundation [PP00P3_146345, P300PB_160969]
- Swiss National Science Foundation (SNF) [P300PB_160969, PP00P3_146345] Funding Source: Swiss National Science Foundation (SNF)
- Bill and Melinda Gates Foundation [OPP1115782, OPP1084519] Funding Source: Bill and Melinda Gates Foundation
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Characterizing polyclonal antibody responses via currently available methods is inherently complex and difficult. Mapping epitopes in an immune response is typically incomplete, which creates a barrier to fully understanding the humoral response to antigens and hinders rational vaccine design efforts. Here, we describe a method of characterizing polyclonal responses by using electron microscopy, and we applied this method to the immunization of rabbits with an HIV-1 envelope glycoprotein vaccine candidate, BG505 SOSIP.664. We detected known epitopes within the polyclonal sera and revealed how antibody responses evolved during the prime-boosting strategy to ultimately result in a neutralizing antibody response. We uncovered previously unidentified epitopes, including an epitope proximal to one recognized by human broadly neutralizing antibodies as well as potentially distracting nonneutralizing epitopes. Our method provides an efficient and semiquantitative map of epitopes that are targeted in a polyclonal antibody response and should be of widespread utility in vaccine and infection studies.
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