FIG 6.

Antibody responses to IC immunogens and uncomplexed trimers are predominantly directed against epitopes in the glycan hole. (A) BG505.T332N virus variants were used to map neutralizing determinants in all sera except those in group A, for which the NAb titers were too low. Determinants involved in neutralizing responses are color coded and were identified by ≥3-fold reductions in NAb titers against variants containing mutations in relevant epitopes. For values that were below the detection limit (ID₅₀ of <30), one-half the cutoff value (ID₅₀ of 15) was used for calculations. Mapping was conducted at Duke University Medical Center. (B) Further mapping was performed at WCMC using BG505 virus mutants with sequence changes affecting V1 (133aN plus 136aA), CD4bs (N356 KI), and a newly identified glycan epitope (N465 KI). RID₅₀ refers to the ID₅₀ against the mutant/ID₅₀ against the parental BG505 strain. REN is the ratio of the extent of neutralization of the mutant versus the parental strain using IgG corresponding to a 1:50 dilution of serum.