Target intelligence / Profile preview

Broadly neutralizing antibody PGDM1400 (PGDM1400) (PGDM1400)

Target
PGDM1400
Molecular classification
Monoclonal antibody, Broadly neutralizing antibody (bnAb), Immunoglobulin G1 (IgG1), Recombinant human antibody
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Overview

PGDM1400 is a human IgG1 broadly neutralizing monoclonal antibody designed to target the glycan-dependent V2 apex region of the HIV-1 envelope glycoprotein trimer (centered at glycan N160). Isolated from a chronically HIV-infected donor, PGDM1400 demonstrates exceptional breadth and potency, neutralizing 83% of tested HIV strains at low concentrations (median IC50 of 0.003 µg/mL). It has been studied as a candidate for both HIV treatment and prophylaxis, either as monotherapy or in combination with other bnAbs (PGT121, VRC07-523LS, etc.) in preclinical animal challenge models and early-phase human clinical trials. As a therapeutic, its mechanisms include direct viral neutralization, Fc-effector functions (ADCC, phagocytosis), and potential engagement of innate immunity. Although PGDM1400 is itself a therapeutic antibody rather than a traditional drug target, its molecular target—the V2 apex of the HIV Env—is a key focus for passive immunotherapy and vaccine development against HIV.

Other names
PGDM1400
02

Mechanism of action

Direct binding to V2 apex region of HIV-1 Env trimer (glycan at N160); Blocks viral entry by inhibiting Env-mediated fusion; Engages Fc-receptors to mediate ADCC and phagocytosis; Passive immunization (direct administration of antibody, not induced by vaccination)

03

Biological functions

Virus neutralizationInhibition of HIV cell-free and cell-to-cell entryAntibody-dependent cellular cytotoxicity (ADCC)Induction of phagocytosis and dendritic cell maturation
04

Disease associations

HIV infectionAcquired immunodeficiency syndrome (AIDS)
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Safety considerations

Risk of viral escape and resistance, especially if used as monotherapyImmunogenicity (development of anti-drug antibodies, rare for human mAbs)General monoclonal antibody safety concerns (infusion reactions, hypersensitivity), but generally well tolerated in trialsIncomplete neutralization in some viral strains
06

Interacting drugs

PGT121

3 more in the full profile.

07

Biomarkers

Serum anti-PGDM1400 antibody titers for pharmacokinetic/effect monitoringHIV-1 RNA viral load (efficacy marker)CD4+ T cell count (general disease monitoring in HIV therapy trials)

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