Fc-dependent functions are redundant to efficacy of anti-HIV antibody PGT121 in macaques

Parsons, Matthew S.; Lee, Wen Shi; Kristensen, Anne B.; Amarasena, Thakshila; Khoury, Georges; Wheatley, Adam K.; Reynaldi, Arnold; Wines, Bruce D.; Hogarth, P. Mark; Davenport, Miles P.; Kent, Stephen J.

doi:10.1172/jci122466

Cited by 70 publications

(83 citation statements)

References 36 publications

(69 reference statements)

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“…Instead, the data support a view that both ART and bNAbs act primarily by limiting viral replication and spread. The greater relative importance of neutralization over Fc function may be especially true in the case of highly potent bNAbs such as PGT121, which was able to protect monkeys from SHIV challenge despite abrogation of Fc receptor binding 48 .…”

Section: Discussionmentioning

confidence: 99%

Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity

et al. 2020

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Vertical transmission accounts for most human immunodeficiency virus (HIV) infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. We showed previously that short-term broadly neutralizing antibody (bNAb) therapy given 24 h after oral exposure cleared simian-human immunodeficiency virus (SHIV) in a macaque model of perinatal infection. Here, we report that all infants given either a single dose of bNAbs at 30 h, or a 21-day triple-drug ART regimen at 48 h, are aviremic with almost no virus in tissues. In contrast, bNAb treatment beginning at 48 h leads to tight control without adaptive immune responses in half of animals. We conclude that both bNAbs and ART mediate effective post-exposure prophylaxis in infant macaques within 30-48 h of oral SHIV exposure. Our findings suggest that optimizing the treatment regimen may extend the window of opportunity for preventing perinatal HIV infection when treatment is delayed.

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Section: Discussionmentioning

confidence: 99%

Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity

et al. 2020

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“…Therefore, Fc receptor functions of antibodies, such as ADCC, may play a crucial role in eliminating these cells (34,63,64). Several studies have demonstrated the importance of Fc receptor function of non-NAbs and bNAbs, although some controversy has recently been raised on the importance of the Fc-mediated function in one study of the mAb PGT121 (65). Recent results from a phase IIa clinical trial of coadministration of romidepsin with 3BNC117 demonstrated no obvious impact on the reduction of viral reservoir or the delay in viral rebound (12), thus support- seronegative and HIV-seropositive donors were obtained by Ficoll gradient from buffy coats.…”

Section: Discussionmentioning

confidence: 99%

Improved killing of HIV-infected cells using three neutralizing and non-neutralizing antibodies

Tuyishime¹,

Garrido²,

Jha³

et al. 2020

Journal of Clinical Investigation

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“…This review highlights the potential role of FcγR-mediated Ab immune functions besides neutralization in protection against HIV. Although the role of the Fc-mediated function of Abs lacking broadly neutralizing activity for HIV protection is still a matter of debate (160,200), numerous independent studies now hint at their relevance for HIV inhibition. Above all, the specific Fc-mediated functions of non-NAbs are the only correlates of protection against infection observed in the RV144 vaccine trial conducted in Thailand (28,29,193,201).…”

Section: Discussionmentioning

confidence: 99%

Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

Dispinseri

Iannone

et al. 2019

Front. Immunol.

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Antibodies (Abs) are the major component of the humoral immune response and a key player in vaccination. The precise Ab-mediated inhibitory mechanisms leading to in vivo protection against HIV have not been elucidated. In addition to the desired viral capture and neutralizing Ab functions, complex Ab-dependent mechanisms that involve engaging immune effector cells to clear infected host cells, immune complexes, and opsonized virus have been proposed as being relevant. These inhibitory mechanisms involve Fc-mediated effector functions leading to Ab-dependent cellular cytotoxicity, phagocytosis, cell-mediated virus inhibition, aggregation, and complement inhibition. Indeed, the decreased risk of infection observed in the RV144 HIV-1 vaccine trial was correlated with the production of non-neutralizing inhibitory Abs, highlighting the role of Ab inhibitory functions besides neutralization. Moreover, Ab isotypes and subclasses recognizing specific HIV envelope epitopes as well as pecular Fc-receptor polymorphisms have been associated with disease progression. These findings further support the need to define which Fc-mediated Ab inhibitory functions leading to protection are critical for HIV vaccine design. Herein, based on our previous review Su & Moog Front Immunol 2014, we update the different inhibitory properties of HIV-specific Abs that may potentially contribute to HIV protection.

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Fc-dependent functions are redundant to efficacy of anti-HIV antibody PGT121 in macaques

Cited by 70 publications

References 36 publications

Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity

Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity

Improved killing of HIV-infected cells using three neutralizing and non-neutralizing antibodies

Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

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