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Enhancing durability of CIS43 monoclonal antibody by Fc mutation or AAV delivery for malaria prevention

JCI Insight. 2020-12; 
Neville Kielau Kisalu, Lais Da Silva Pereira, Keenan J Ernste, Yevel Flores-Garcia, Azza H Idris, Mangaiarkarasi Asokan, Marlon Dillon, Scott MacDonald, Wei Shi, Xuejun Chen, Amarendra Pegu, Arne Schön, Fidel Zavala, Alejandro B Balazs, Joseph R Francica, Robert A Seder
Products/Services Used Details Operation
Mutagenesis Services … 17 Methods 335 Site-directed mutagenesis and rPfCSP probes generation 336 CIS43LS was generated through site-directed mutagenesis (GenScript) … protein (NCBI gene ID: PF3D7_0304600) of 3D7, a clone of the NF54 strain of P. falciparum, 339 was used (GenScript) … Get A Quote

摘要

CIS43 is a potent neutralizing human monoclonal antibody (mAb) that targets a highly conserved 'junctional' epitope in the Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP). Enhancing the durability of CIS43 in vivo will be important for clinical translation. Here, two approaches were used to improve the durability of CIS43 in vivo while maintaining potent neutralization. First, the Fc domain was modified with the "LS" mutations (CIS43LS) to increase CIS43 binding affinity for the neonatal Fc receptor (FcRn). CIS43LS and CIS43 showed comparable in vivo protective efficacy. CIS43LS had nine to thirteen-fold increased binding affinity for human (6.2 nM vs. 54.2 nM) and rhesus (25.1 nM vs. 325.8 nM) FcRn... More

关键词

Immunoglobulins, Infectious disease, Malaria, Skin