HIV-1 Env-specific IgA/IgG ratio is related to antibody dependent cellular cytotoxicity (ADCC) responses observed during acute/early HIV infection.

MARÍA JULIA RUIZ; YANINA GHIGLIONE; JULIANA FALIVENE; NATALIA LAUFER; MARÍA EUGENIA SOCIAS; PEDRO CAHN; OMAR SUED; HORACIO SALOMÓN; MARÍA MAGDALENA GHERARDI; GABRIELA TURK

Ciudad del Cabo

Conferencia; HIV-R4P. Research for Prevention; 2014

Global HIV Vaccine Enterprise

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) 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 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) 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