PD05.04
Background: Immune correlates analysis of the RV144 vaccine trial revealed that high levels of Env specific IgA antibodies (ab) may have mitigated the capacity of protective vaccine-induced IgG ab to mediate ADCC.
Aim: To evaluate the relation between Env-specific IgG and IgA ab and ADCC responses in the context of acute/early primary HIV infection (PHI).
Methods: Plasma from 20 HIV+ subjects enrolled during PHI, obtained at enrollment (baseline sample) and 1 year post-infection sample (ypi), 10 HAART-naïve chronically infected patients (C) and 7 Elite Controllers (EC) were used. Percentage of ADCC-killing was determined using the rapid and fluorometric ADCC assay. Env-specific IgG and IgA ab were assessed by ELISA. Data was analyzed using non-parametric statistics.
Results: Levels of Env-specific IgG ab were significantly higher in PHI ypi sample compared to baseline (median 2802 vs 24902 ng/ml p=0.006) and as expected directly correlated with %ADCC-killing both at baseline (r=0,476 p=0,039) and ypi samples (r=0,627 p=0,016). Similar direct correlations were observed in C and EC (r=0,898 p=0,033 and r=0,766 p=0,021 respectively). Conversely, IgA titers declined over the course of acute infection (baseline vs ypi: 200 vs 35 respectively, p=0,001) and did not correlate with ADCC responses observed at the ypi sample. Env-specific IgG/IgA ratios were also significantly higher at the ypi sample compared to baseline (median 556,5 vs 10,39, respectevly, p=0,0001). More interestingly, Env-specific IgG/IgA ratios directly correlated with %ADCC-killing at the ypi sample (r=0,538 p=0,047).
Conclusions: The direct correlation between IgG/IgA ratio and %ADCC-killing observed at the ypi sample indicate that Env-specific IgA ab might be interfering with the magnitude of IgG-mediated ADCC responses in subjects undergoing PHI. This result indicates that the elicitation of Env-specific IgA ab hampers protective ADCC responses not only in vaccinees but also in natural infection and should be taken into account in vaccine settings.
