Antibodies induced lysis of primary infected cells by ADCC is HIV-1 strain specific

BIEDMA, M.E; DECOVILLE, T; SU, B; MOOG, C

Ciudad del Cabo

Conferencia; HIV Research for Prevention 2014; 2014

Understanding immune responses aiming to control or prevent HIV-1 infection is fundamental for the design of vaccine strategies. Increasing evidences suggest that antibodies (Abs) bound to innate immune effector cells may play a role in protection from infection. Antibody-dependent cellularcytotoxicity (ADCC) mediated by Natural Killer (NK) cells is a complex process involving Abs that bridge infected target cells with FccRIII bearing NK cells. This binding results in cell lysis, besides direct lysis as part of innate NK cell-mediated mechanism. In this study, the antiviral contribution of ADCC was investigated using physiologically relevant conditions on primary HIV-1 infected CD4T cells and using autologous primaryNK cells. Methods: We infected CD4+enriched T-cells with different HIV-1 R5 isolates to record 20% infected cells. Autologous NK cells were at an effector to target ratio of 1:1. To get rid of direct lysis of infected cells by NK, the percentage of infected cells was determined by flow cytometry after 4h incubation in the presence (ADCC) or in the absence (direct lysis) of Abs. Results:We found that effector NK cells display potent reduction of HIV-1 infected target cells by polyclonal and monoclonal Abs beyond the direct lysis observed in the absence of Abs. Interestingly, the extent of ADCC was highly dependent on the virus strain used suggesting that vaccine should induce Abs with broad ADCC as for Ab neutralization. Moreover, the percentage of cell lysis recorded was different to that obtained by analyzing surrogate marker of ADCC in vitro as NK CD107a expression levels or measurement of effector molecules delivered into target cells. Conclusions: Detection of lysis of primary infected cells support the potential in vivo role of ADCC as additional inhibitory mechanism involved in protection and highlight the necessity to further compare the currently used ADCC assays for theirphysiological relevance in protection against HIV-1