Abstract
Elite controllers (ECs) represent a unique model of a functional cure for HIV-1 infection as these individuals develop HIV-specific immunity able to persistently suppress viremia. Because accumulating evidence suggests that HIV controllers generate antibodies with enhanced capacity to drive antibody-dependent cellular cytotoxicity (ADCC) that may contribute to viral containment, we profiled an array of extra-neutralizing antibody effector functions across HIV-infected populations with varying degrees of viral control to define the characteristics of antibodies associated with spontaneous control. While neither the overall magnitude of antibody titer nor individual effector functions were increased in ECs, a more functionally coordinated innate immune–recruiting response was observed. Specifically, ECs demonstrated polyfunctional humoral immune responses able to coordinately recruit ADCC, other NK functions, monocyte and neutrophil phagocytosis, and complement. This functionally coordinated response was associated with qualitatively superior IgG3/IgG1 responses, whereas HIV-specific IgG2/IgG4 responses, prevalent among viremic subjects, were associated with poorer overall antibody activity. Rather than linking viral control to any single activity, this study highlights the critical nature of functionally coordinated antibodies in HIV control and associates this polyfunctionality with preferential induction of potent antibody subclasses, supporting coordinated antibody activity as a goal in strategies directed at an HIV-1 functional cure.
Highlights
Vaccine-mediated protection from HIV-1 infection has been observed in humans in association with extra-neutralizing antibody functions, including the ability to induce effector functions such as antibody-dependent cellular cytotoxicity (ADCC) [1]
In contrast to previous studies, enhanced functional activity among Elite controllers (ECs) was not observed for any individual Fc-effector function compared to viremic controllers (VC), CTs, or CUs (Fig 1A–1G)
Antibody-dependent complement deposition (ADCD) was highly positively correlated with all other functions in ECs, but generally had no or only weak correlation with the other functions, in the viremic subject groups (VC and CU)
Summary
Vaccine-mediated protection from HIV-1 infection has been observed in humans in association with extra-neutralizing antibody functions, including the ability to induce effector functions such as antibody-dependent cellular cytotoxicity (ADCC) [1]. As HIV-1 controllers represent an alternative vaccine goal—the induction of immunity able to contain viral replication subsequent to infection—these data suggest that beyond cellular correlates associated with control [11,12], antibodies with enhanced ability to direct the potent anti-viral activities of innate effector cells may contribute to a functional cure. Evidence from both protected vaccinees and spontaneous HIV-1 controllers converges on a potential role for non-neutralizing antibody responses with the capacity to direct the cytolytic activity of the innate immune system in viral control and clearance. While IgG3-driven antibody polyfunctionality was associated with reduced risk of infection in the RV144 vaccine trial [15,16], the specific humoral profiles that associate with antibody-mediated viral containment in the setting of durable control of infection are unknown
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
