Higher Baseline ADCC Responses in Chronic Nonprogressive HIV Infection Are Associated with Reduced HIV Burden in Later Course of Disease.

The importance of anti-HIV antibodies mediating antibody-dependent cell-mediated cytotoxicity (ADCC) in protective immunity against HIV is recognized recently. The purpose of this study was to measure the functional ADCC response at different stages of HIV infection in a well-defined HIV+ cohort, including 20 recently infected individuals, 30 with long-term slow-progressive, 24 with short-term slow-progressive and 32 with progressive HIV infection using a rapid fluorometric ADCC assay. The antibodies mediating ADCC were found in all disease stages. These antibodies were detectable at as early as 25 days after the estimated date of infection, however, did not influence the viral load set point probably indicating no major influence on the early course of the disease. However, the frequency and magnitude of functional ADCC responses were associated with higher CD4+T cell count and lower viral load and were significantly lower in progressors compared with other groups. The usefulness of the ADCC responses in longer viral control was assessed in a subset of participants with slowly progressing HIV infection. In these individuals, the ADCC responses observed at the visit 1 were found to be increased over time and were associated with lower plasma viral load estimated 4 to 15 years later in the disease course. Overall, the study findings confirm the role of ADCC antibodies in reducing the viral burden and also indicate the probable role of sustained functional ADCC responses in reducing the viral burden during the later period of HIV infection.

FcγRIIIa receptor polymorphism influences NK cell mediated ADCC activity against HIV.

BACKGROUND: HIV-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance. The ADCC is mediated primarily by natural killer cell activated through the binding of FcγRIIIa receptor to the Fc portion of antibody bound to the antigen expressed on the infected cells. However, no data is available on the influence of the polymorphism in FcγRIIIa receptor on HIV-specific ADCC response. METHODS: The Sanger's method of sequencing was used to sequence the exon of FcγRIIIa receptor while the ADCC activity was determined using NK cell activation assay. The polymorphism in FcγRIIIa receptor was assessed in HIV-infected Indian individuals with or without HIV-specific ADCC antibodies and its influence on the magnitude of HIV-specific ADCC responses was analyzed. RESULTS: Two polymorphisms: V176F (rs396991) and Y158H (rs396716) were observed. The Y158H polymorphism is reported for the first time in Indian population. Both, V176F (V/V genotype) (p = 0.004) and Y158H (Y/H genotype) (p = 0.032) were found to be significantly associated with higher magnitude of HIV-specific ADCC response. CONCLUSION: The study underscores the role of polymorphism in the FcγRIIIa receptor on HIV-specific ADCC response and suggests that the screening of the individuals for FcγRIIIa-V176F and Y158H polymorphisms could be useful for prediction of efficient treatment in monoclonal antibody-based therapies aimed at ADCC in HIV infection.