Support women in science at Burnet Institute
Donate today to support women in science at Burnet and their work to unlock the vaginal microbiome and reduce risk of HIV infection and preterm birth for women around the world.
Donate today to support women in science at Burnet and their work to unlock the vaginal microbiome and reduce risk of HIV infection and preterm birth for women around the world.
Background
There is growing interest in immune therapies to clear the latent HIV-1 after combination antiretroviral therapy (cART). There is limited information on the effect of cART on antibody-dependent cellular cytotoxicity (ADCC) and no studies have directly compared ADCC in HIV-1 subtype B- and subtype C-infected subjects. The effect of improving immunocompetence on ADCC to influenza also remains unexplored.
Methods
The effect of cART on HIV-1- and influenza-specific ADCC was analyzed in two cohorts (39 subtype B- and 47 subtype C-infected subjects) before and after two years of cART. ADCC analyses included an ELISA-based dimeric recombinant soluble (rs) FcγRIIIa-binding assay, antibody-dependent natural killer (NK) cell activation assay and ADCC-mediated killing assays.
Results
HIV-1 subtype B and C Env-specific antibody binding to dimeric rsFcγRIIIa were reduced in subtypes B- and C-infected cohorts after two years of cART (both p<0.05). Reduced ADCC-mediated killing of target cells expressing subtype B Env in the subtype B-infected cohort (p=0.003) was observed after 96 weeks of cART, but not of subtype C Env in the subtype C-infected cohort. A greater reduction in ADCC was detected in subjects with baseline CD4 counts >300 cells/μl (p<0.05). The resolving immunodeficiency after 96 weeks of cART resulted in improved HA-specific ADCC to six strains of influenza (all p<0.01).
Conclusions
cART results in HIV-1 antigen loss and reductions in HIV-1 Env-specific antibodies with Fc functionality in both subtype B- and C-infected subjects, particularly in immunocompetent subjects. Simultaneously, cART improves ADCC to diverse strains of influenza, suggesting reduction in influenza disease after cART.