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A key difficulty in developing a global HIV vaccine is the tremendous diversity of HIV strains. Hypothetically, a vaccine could overcome this challenge by inducing antibodies capable of neutralizing a broad array of HIV variants from around the world. Such broadly neutralizing antibodies (BnAbs) have been isolated from individuals chronically infected with HIV and target highly conserved regions on the HIV envelope, such as the CD4-binding site. Mature CD4-binding site BnAbs have high levels of somatic mutation resulting from prolonged antigen exposure and may be very difficult to elicit with traditional vaccine strategies. However, knowledge about how BnAbs evolve in the presence of antigen might allow the design of novel vaccines to guide…