Stam, Jord C. and de Maat, Steven and de Jong, Dorien and Arens, Mathia and van Lint, Fenna and Gharu, Lavina and van Roosmalen, Mark H. and Roovers, Rob C. and Strokappe, Nika M. and Wagner, Ralf and Kliche, Alexander and de Haard, Hans J. and Henegouwen, Paul M. van Bergen en and Nijhuis, Monique and Verrips, C. Theo (2022) Directing HIV-1 for degradation by non-target cells, using bi-specific single-chain llama antibodies. SCIENTIFIC REPORTS, 12 (1): 13413. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
While vaccination against HIV-1 has been so far unsuccessful, recently broadly neutralizing antibodies (bNAbs) against HIV-1 envelope glycoprotein were shown to induce long-term suppression in the absence of antiretroviral therapy in patients with antibody-sensitive viral reservoirs. The requirement of neutralizing antibodies indicates that the antibody mediated removal (clearance) of HIV-1 in itself is not efficient enough in these immune compromised patients. Here we present a novel, alternative approach that is independent of a functional immune system to clear HIV-1, by capturing the virus and redirecting it to non-target cells where it is internalized and degraded. We use bispecific antibodies with domains derived from small single chain Llama antibodies (VHHs). These bind with one domain to HIV-1 envelope proteins and with the other domain direct the virus to cells expressing epidermal growth factor receptor (EGFR), a receptor that is ubiquitously expressed in the body. We show that HIV envelope proteins, virus-like particles and HIV-1 viruses (representing HIV-1 subtypes A, B and C) are efficiently recruited to EGFR, internalized and degraded in the lysosomal pathway at low nM concentrations of bispecific VHHs. This directed degradation in non-target cells may provide a clearance platform for the removal of viruses and other unwanted agents from the circulation, including toxins, and may thus provide a novel method for curing.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BROADLY NEUTRALIZING ANTIBODIES; ANTI-HIV-1 ANTIBODIES; BISPECIFIC ANTIBODIES; INHIBITION; ENDOCYTOSIS; THERAPY; VIREMIA; TRAFFICKING; COMBINATION; INFECTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Feb 2024 06:44 |
| Last Modified: | 02 Feb 2024 06:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58308 |
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