HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice

Abstract

Effective control of HIV-1 infection in humans is achieved using combinations of antiretroviral therapy (ART) drugs. In humanized mice (hu-mice), control of viremia can be achieved using either ART or by immunotherapy using combinations of broadly neutralizing antibodies (bNAbs). Here we show that treatment of HIV-1-infected hu-mice with a combination of three highly potent bNAbs not only resulted in complete viremic control but also led to a reduction in cell-associated HIV-1 DNA. Moreover, lowering the initial viral load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn. Similarly, a single injection of adeno-associated virus directing expression of one bNAb produced durable viremic control after ART was terminated. We conclude that immunotherapy reduces plasma viral load and cell-associated HIV-1 DNA and that decreasing the initial viral load enables single bNAbs to control viremia in hu-mice.CD4bs | glycan | gp160

Antibody functional assays as measures of Fc receptor-mediated immunity to HIV - new technologies and their impact on the HIV vaccine field.

“…Recently, a human leukocyte reconstituted mouse model was developed to assess antibody mediated protection by neutralisation [43] and activating FcγR-dependent mechanisms [44]. The full potency of bNAbs in protection and control of viremia has been shown in this model to require FcγR-dependent extra-neutralising activity [44].…”

In vivo platforms for analysis of HIV persistence and eradication

“…The human cells present in these animals have been shown to induce both innate and adaptive immune responses (46,53,(58)(59)(60)(61). In addition, HIV infection in these models responds to the same drugs used in humans (62)(63)(64)(65)(66)(67)(68). Like all animal models for biomedical research, there are limitations to their use in HIV research.…”

Exploring the Potential of Monoclonal Antibody Therapeutics for HIV-1 Eradication

“…Likewise, recent animal studies have shown that broadly neutralizing antibodies are indeed effective therapeutically. [78][79][80][81] In a human primate study, 3 out of 18 monkeys that exhibited the lowest viral loads prior to treatment exhibited prolonged virological control after the animals were treated with a PGT121-containing mAb cocktail and virus was cleared from the blood. However, while these mAbs cleared systemic virus transiently, the mAbs were unable to eradicate the reservoir in the majority of animals.…”