Natural killer cells mediated antibody dependent cellular cytotoxicity response in acute and recovery phases of chikungunya

Background Neutralizing antibody is reported to correlate with protection from symptomatic chikungunya disease. In addition to direct virus neutralization, virus-specific antibodies can also protect through antibody effector functions via antibody-dependent cellular cytotoxicity (ADCC) mechanism. Methods We have assessed NK cell-mediated chikungunya virus (CHIKV) specific ADCC response in 56 acute, 56 prolonged, 44 chronic chikungunya arthritis patients, 23 recovered individuals from chikungunya (CHIK) & 50 healthy controls using a flow cytometry-based antibody-dependent heterologous NK cell activation assay with ADCC surrogate markers CD107a & IFN-γ. Results Persistent ADCC response in recovered individuals spanning over a duration of 3 months to 18 years post-infection and progressive decline in ADCC response in chronic chikungunya arthritis patients over the period of time were observed. ADCC response correlated with lower plasma viral load in acute patients ( p =0.022, r=-0.709). Recovered individuals elucidated a positive correlation between ADCC response and plasma anti-CHIKV IgG and IgG3 antibody levels (IgG: r=0.4503, IgG3: r=0.4583, p -value<0.01 in each). Conclusion Overall, the current study establishes the prognostic role of NK cells-mediated ADCC response in chikungunya infection. In a nutshell, these findings provide a base for future antibody-based therapeutics for chikungunya utilizing IgG3 antibody that has functional ADCC capacity. Graphical Abstract Highlights NK cells play key role in chikungunya infection NK cells mediated ADCC response remain unexplored in chikungunya Anti-CHIKV IgG3 antibody dependent activation of the NK cells observed Efficient NK cells mediated ADCC response detected in acute & recovery phases of chikungunya IgG3 with functional ADCC capacity can direct Ab-based therapeutics design in chikungunya