Figure 3. Non-neutralizing Abs Contribute to Reduced Risk of Infection.
(A and B) Direct correlation of CH505 bAb titers (AUC, log10) and the number of SHIV.CH505 exposures to infection plotted using plasma after (A) third vaccination and (B) summarized for all Env antigens after third and fourth vaccinations. No correlations were found after the fifth and sixth vaccinations. p values (Spearman) are listed, p values in parentheses indicate trend.
(C) NAbs to tier-1A CH505.w4.3 (upper panel) and the tier-2 CH505.TF (lower panel) measured in serum 2 weeks after the third to sixth vaccinations. Black dotted line indicates the limit of detection (LOD) of neutralization in the TZM-bl assay. CH505.w4.3 differs from the tier-2 CH505.TF by a single point mutation (W663G), located in the MPER (membrane-proximal extracellular region).
(D) Binding of Env-Abs exposed on the surface of HIV.CH505 infected cells measured by the infected cell Ab binding assay (ICABA) showing MFI of the two vaccine groups. p values are from Wilcoxon test (statistical analysis software).
(E and F) Correlation between ADCC peak (maximum % GrzB activity) and number of SHIV CH505 exposures to infection (E) after third vaccination and (F) summary of correlations measured after third and fourth vaccinations. No correlations were found with the peak ADCC after fifth and sixth vaccinations. p values (Spearman) are given.
(G) Binding of CH505-Env-specific Abs to FcγRIIIa1.
(H and I) Direct correlations between ADCC titers and CH505.TF-specific Ab binding to FcγRIIIa1 and FcγRIIIa3 showing correlation between (H) CH505.TF gp120 Abs and FcγRIIIa1 and (I) different CH505 Abs binding to FcγRIIIa3 after sixth vaccination. Spearman R and p values are given.