A vaccine strategy for inducing broadly neutralizing antibodies against HIV

An effective HIV vaccine must induce broadly neutralizing antibodies (bnAbs) that target the most conserved sites of the HIV envelope, a feat that has not yet been achieved in humans. Germline-targeting vaccine design holds promise by using immunogens to prime naive B cells for bnAb precursor activation and then boosting their maturation. A major challenge for this approach is that antibodyantigen recognition depends on a long heavy chain complementarity determining region 3 (HCDR3) loop on naive B cells, which is present at very low frequencies. Two papers in Science describe an immunization strategy that effectively primes and boosts maturation of B cell precursors to produce the HCDR3-dominant bnAb BG18.

In the first study, Steichen et al. used the priming immunogen N332-GT5 to target BG18 precursors in rhesus macaques. Immunization with N332-GT5 and adjuvant saponin/MPLA nanoparticles reliably induced diverse BG18-class precursors in all eight animals. Structural analysis confirmed the binding of antibodies with BG18-class HCDR3s to HIV trimer glycoproteins, similar to BG18.

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