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

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

Ciudad del Cabo

Congreso; HIV Research for Prevention Conference; 2014

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 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 statisticsLevels of Env-specific IgG ab were significantly higher in PHI ypi sample compared to baseline and as expected directly correlated with %ADCC-killing both at baseline and ypi samples. Similar direct correlations were observed in C and EC . Conversely, IgA titers declined over the course of acute infection (band 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 . More interestingly, Env-specific IgG/IgA ratios directly correlated with %ADCC-killing at the ypi sample. 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