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Atoltivimab is part of a product containing three monoclonal IgG1κ antibodies directed against the GP1,2 glycoprotein of Zaire ebolavirus. Together, these three antibodies act to neutralize viral particles and to recruit immune effectors for the destruction of both viral particles and infected cells.
Atoltivimab is part of a product containing three monoclonal IgG1κ antibodies directed against the GP1,2 glycoprotein of Zaire ebolavirus. Together, these three antibodies act to neutralize viral particles and to recruit immune effectors for the destruction of both viral particles and infected cells.
Ebola virus (EBOV) is one of several viruses within the Ebolavirus genus known to infect humans with an average case fatality rate of 43.92%. EBOV particles expose the GP glycoprotein on their surface, which comprises a trimer of GP and GP subunit heterodimers, with the subunits connected by a disulfide bond. GP plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP is integral to the pathogenic cycle of EBOV. Atoltivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the EBOV GP glycoprotein, which binds the GP glycan cap parallel to the viral surface with a binding affinity (K) of between 7.74 and 7.84 nM. Atoltivimab exhibits strong (<90%) neutralization of chimeric lentiviral particles expressing EBOV GP with a half-maximal inhibitory concentration (IC) value of 0.27 nM. In addition, Atoltivimab is capable of dose-dependent activation of FcγRIIIa signalling in effector cells in the presence of GP-expressing cells with a half-maximal effective concentration (EC) of 2.9 nM. Combined with Odesivimab and Maftivimab, Atoltivimab works to block EBOV cell infection and lysosomal escape, as well as the potential antibody-dependent cell-mediated killing of EBOV-infected cells.
Atoltivimab is indicated in combination with Odesivimab and Maftivimab for the treatment of Zaire ebolavirus infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for Zaire ebolavirus infection. This combination has not been established as efficacious for any other species within either the Ebolavirus or Marburgvirus genera; special care should be taken to evaluate the susceptibility of circulating Zaire ebolavirus strains before beginning treatment, and the possible emergence of resistance should be monitored.
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