Refined identification of neutralization-resistant CRF02_AG viruses and their sensitivity to anti-MPER neutralizing antibodies

Results Sensitivity to South Africa sera by subtype was C>B≈CRF02_AG>A. Importantly, and in contrast to previous reports, CRF02_AG plasma neutralized CRF02_AG viruses better than other panel viruses (“within-subtype neutralization”). This included three (257-31, 251-18 and 33-7) of five CRF02_AG viruses previously designated as tier 3 (most resistant). This within-subtype neutralization testing showed that the other two tier 3 CRF02_AG panel viruses, 253-11 and 278-50 were highly resistant. Most CRF02_AG viruses, including 253-11 and 278-50 were sensitive to two membrane proximal external region (MPER)-specific monoclonal antibodies and soluble CD4 (sCD4), suggesting targets for neutralization of even these highly resistant viruses. This information may help design a global HIV-1 vaccine. We also propose testing viruses with within-subtype samples selected for good neutralizers in order to evaluate their neutralization resistance.