VivoGenie Anti-Human CD4 (Ibalizumab) Biosimilar (IVMB0499)

CD4 is a cell surface glycoprotein essential for both T cell activation and human immunodeficiency virus type-1 (HIV-1) infection ^1,2. CD4 consists of an extracellular segment composed of four tandem immunoglobulin-like domains (D1 to D4), a single transmembrane span, and a short C-terminal cytoplasmic tail ¹. HIV-1 entry into host CD4 cells is a complex process that occurs through the interaction of HIV-1 glycoprotein 120 (gp120) with extracellular CD4 D1 ^3,4. When gp120 binds to CD4, a conformational shift occurs that allows co-receptors to bind to the gp120/receptor complex, leading to viral fusion and entry. Ibalizumab is the first CD4-directed post-attachment HIV-1 entry inhibitor and prevents entry of a broad spectrum of HIV-1 isolates ^1,5,6,7,8.

Ibalizumab selectively binds to an epitope on CD4 D2 (residues 121-124 and 127-134 ⁹ and especially L96, P121, P122, and Q163 ^1,7) as well as residues E77 and S79 on D1 at the interface between D1 and D2 4,7. Ibalizumab primarily contacts the BC-loop in D2 at the D1-D2 junction on the opposite side to the gp120 and major histocompatibility complex II (MHC-II) binding sites ². Ibalizumab does not inhibit HIV-1 gp120 binding to D1, but instead induces conformational changes that via steric hindrance block gp120 and HIV co-receptors from interacting, thereby preventing viral fusion and entry ^3,4,7,10,11. Additionally, because the cellular epitope is distant from the D1 MHC-II binding site ⁴, MHC-II mediated immunosuppression is prevented ³. Furthermore, as a humanized IgG4 antibody, ibalizumab displays low affinity for C1q and FcɣRI receptors of natural killer cells and consequently has low cellular cytotoxic dependent activity and no Fc-mediated CD4+ T cell depletion ³.

Ibalizumab was derived from mu5A8 by grafting the mouse complementary-determining region onto a human IgG4 construct ^1,3,12. The chemical name is immunoglobulin G4, anti-(human CD4 (antigen)) (human-mouse monoclonal 5A8 γ4-chain), disulphide with human-mouse monoclonal 5A8 κ-chain, dimer ⁵.