The authors compared the potential of eight broadly neutralising antibodies (bnAbs) and two bispecific Abs currently under clinical development to prevent infection by dominant HIV subtypes in sub-Saharan Africa. They used in vitro neutralisation data for Abs against 25 subtype A, 100 C and 20 D pseudoviruses to model neutralisation by single Abs and two-Ab combinations. IC80 breadth-potency, completeness of neutralisation and simultaneous coverage by both Abs in the combination were used to classify prevention potential. The authors also predicted the in vivo protection provided by the Abs by modelling protection as a function of in vitro neutralisation based on data from a macaque SHIV challenge study. The authors found that nearly complete neutralisation of a given virus is needed for in vivo protection (~98% neutralisation for 50% relative protection). Therefore, on this basis, bnAb combinations should outperform single bnAbs but different combinations work best for different subtypes. A single bispecific 10E8-iMAb targeting HIV Env and host-cell CD4 was better than all combinations of two conventional bnAbs, with 95–97% predicted relative protection across subtypes. Combinations that included 10E8-iMAb were even more effective than 10E8-iMAb alone. Therefore the use of 10E8-iMAb in combination to prevent HIV-1 infections in sub-Saharan Africa is very promising.
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