The authors were interested in how HIV-1-specific broadly neutralising antibodies (bNAbs) can be elicited and the potential of passively delivered bNAbs for prophylaxis and therapeutics. They used neutralisation data from four large virus panels to map viral signatures associated with bNAb sensitivity, including amino acids, hypervariable region characteristics and clade effects across four different classes of bNAbs. The bNAb signatures defined for the variable loop 2 (V2) epitope region of HIV Env could then be used to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. The authors introduced V2 bNAb signature-guided mutations into Env 459C to create a trivalent vaccine and then immunised guinea pigs with these V2-SET vaccines, resulting in increased breadth of NAb responses compared with Env 459C alone. Therefore bNAb signatures can be used to produce HIV Env vaccine immunogens that are capable of eliciting antibody responses with greater neutralisation breadth.
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