Adeno-associated virus (AAV) vectors that express HIV-1 broadly neutralizing antibodies (bNAbs) have had limited success owing to the large proportion of HIV-1 isolates that remain partially or wholly resistant to bNAbs. Gardner et al. now present a new approach in which bNAbs are replaced with a fusion protein that mimics the virus receptor CD4 and its co-receptor CCR5, which bind to the two most conserved epitopes in the HIV-1 Env protein, thereby facilitating host-cell entry. Compared with a CD4 mimic alone, the fusion protein resulted in a 20–200-fold increase in viral neutralization, and the targeting of only the most conserved epitopes resulted in the neutralization of a diverse panel of HIV-1, HIV-2 and SIV isolates. A 40-week trial of this new AAV vector in rhesus macaques demonstrated durable protection against SHIV with no adverse effects.
References
Gardner, M. R. et al. AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges. Nature http://dx.doi.org/10.1038/nature14264 (2015)
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Attar, N. Better protection against HIV. Nat Rev Microbiol 13, 186 (2015). https://doi.org/10.1038/nrmicro3462
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DOI: https://doi.org/10.1038/nrmicro3462