Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization
Fig 5
Role of the glycan at position 332 (N332+) in influencing neutralization susceptibility of clade C viruses.
Each point represents the geometric mean of viruses tested for neutralization sensitivity using either bnAbs (A) or a panel of 30 South African sera (B and C). (A) Comparison of neutralization sensitivity of clade C viruses to bnAbs VRC01, PG9, PGT128, CAP256-VRC26.25 and 4E10. The highest concentration tested for each bnAb and the percentage of viruses neutralized (breadth) are indicated. Env pseudotyped clade C viruses (n = 139), from single infections for which SGA-derived sequences were available, were partitioned into three infection stage groups per sequential gain of HIV-1 specific antibody responses as a marker of time from infection; pre-seroconversion (Ab-), indeterminate (Ab-/+) and post-seroconversion (Ab+). Throughout, pre-seroconversion viruses are indicated in blue, with indeterminate in grey and post-seroconversion in red. Significant differences between medians indicated with the relevant p-value for a two-sided Mann-Whitney test. (B) Comparison of glycan frequency changes between pre-seroconversion (Ab-) and post-seroconversion (Ab+) infection stages for six sites comprising the glycan patch [57]. N-linked glycans were predicted according to the Nx(T/S) sequon, where x is not a proline. (C) Comparison of neutralization sensitivity between viruses categorized into those containing N332+ (n = 94), those with N334+ (n = 22) and those without a glycan at either position 332 or 334 (n = 21). Significance tested and shown with p-values provided for a Mann-Whitney, two-sided test. (D) A comparison of susceptibility using only viruses containing the N332 glycan, per infection stage. Dot plots show medians in red horizontal lines and interquartile ranges in black lines. Significance tested by non-parametric two-sided Mann-Whitney tests. Uncorrected p-values are provided.