Two new studies reveal that administering a potent, broadly neutralizing antibody that binds to HIV evokes a strong immune response in humans, and can even accelerate the clearance of infected cells. First, Till Schoofs et al. analyze results from a clinical trial where a single injection of a type of broadly neutralizing antibody (bNAb) called 3BNC117 was administered to 15 HIV patients, nearly all of whom experienced a reduction in viral loads that lasted for some time - all but one of the HIV-positive individuals infused with the bNAb showed increased breadth and/or potency against the virus at 24 weeks, with the effects ranging from small to dramatic. Intriguingly, the virus appears to develop resistance to 3BNC117 at 24 weeks, and yet Immunoglobulin G (IgG), a key protein in humans that specifically recognizes and binds to particular antigens, was found to have a stronger general response to both 3BNC117-sensitive and 3BNC117-resistant strains of HIV 24 weeks after 3BNC117 injection. While 3BNC117 clearly enhances host immune responses to HIV, the reasons remain largely enigmatic.
A separate analysis of 3BNC117 by Ching-Lan Lu et al. reveals that the antibody not only blocks infection of new cells, but accelerates the clearance of infected cells as well. Early in their study, the team noticed differences between the expected 3BNC117 abundance in humans over time, given its half-life, and the actual abundance, a discrepancy hinting that some of the antibodies may be targeting not just circulating virus particles but HIV-infected cells as well. Experiments in mice confirmed that 3BNC117 can accelerate clearance of HIV-1-infected cells in vivo, and clearance was also observed in T cells isolated from patients. Next, Lu et al. found that 3BNC117 was not effective at clearing infected cells when their Fcγ receptor was mutated or blocked, suggesting that this receptor is a key mechanism behind 3BNC117-mediated clearance of HIV-infected cells. Collectively, these studies suggest that the bNAb 3BNC117 could be a viable therapeutic target for HIV.
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Journal
Science