Abstract
Human Immunodeficiency Virus (HIV) initiates infection in host T-cells by binding with CD4 molecules on the cell surface, otherwise known as the primary cell receptor. Human CD4 molecules may therefore be able to assist the host immune system in mounting an immune defense, in controlling immune homeostasis and during immune monitoring. Indeed, anti-CD4 reagents could be used to perturb the HIV–CD4 interaction and thereby directly neutralize and inhibit HIV through surface glycoproteins. At present, various anti-CD4 antibodies have been shown to block HIV-1 infection with genotype-broad and highly effective features, some of which have been further tested in clinical trials. Here, we review some of the more potent anti-CD4 antibodies isolated to date, and focus on the molecular insights gained from the understanding of the binding of monoclonal antibodies (mAbs) to the CD4 D1 (mAb 15A7) and D2 (Ibalizumab) domains. These salient points may aid in the design of better anti-CD4 reagents for HIV treatment.
Highlights
Human CD4 is a single-chain, trans-membrane glycoprotein belonging to the immunoglobulin superfamily that is mainly expressed on T lymphocytes, B lymphocytes and thymocytes
An evaluation in vivo indicates that ibalizumab shows an effective ability to decrease plasma viral loads and increase CD4+ cell counts in Human Immunodeficiency Virus (HIV)-1-infected patients and rhesus monkeys infected with simian immunodeficiency virus [28]
Considering that bi-specific antibodies have been successful in the clinic, the wide and potent neutralizing activities of PG9-iMab and PG16-iMab suggests its suitability as a candidate immunization therapy for HIV-1 treatment [36]
Summary
The mAb 15A7 demonstrates a mild binding affinity to other D2 antibodies, which indicates humanized and affinity maturation should be implemented in future applications. Earlier reports showed that Mu5A8 acts synergistically with an anti-gp120 V3 loop antibody, NEA-9205, to inhibit the virus and cell membrane fusion [23].
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