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bnAbs for HIV: shepherding towards improbable mutations

  1. Alexandra Flemming
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The discovery of broadly neutralizing antibodies (bnAbs) to HIV in rare HIV-positive individuals indicated that it should be possible to design effective vaccines. However, this has proven to be exceptionally challenging since HIV-targeted bnAbs tend to have many unusual features, including ‘improbable mutations’ located outside the normal mutation hotspots. Moreover, the inferred precursors of the known bnAbs typically have no detectable affinity for the virus. Therefore, vaccination strategies need to first prime B cells encoding bnAb precursors, followed by immunogens that shepherd antibody affinity maturation towards the acquisition of unusual features. Two reports in Science now demonstrate the design of immunogens for such a vaccine strategy.

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Nature Reviews Drug Discovery 19, 90 (2020)

doi: https://doi.org/10.1038/d41573-020-00005-3

This article originally appeared in Nat. Rev. Immunol. (https://doi.org/10.1038/s41577-019-0270-0).

References

  1. Steichen, J. M. et al. A generalized HIV vaccine design strategy for priming broadly neutralizing antibody responses. Science 366, eaax4380 (2019)

    PubMed  Google Scholar 

  2. Saunders, K. O. et al. Targeted selection of HIV-specific antibody mutations by engineering B cell maturation. Science 366, eaay7199 (2019)

    PubMed  Google Scholar 

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