Epitope Mapping of the Anti-California Sea Lion Podoplanin Monoclonal Antibody PMab-269 Using Alanine-Scanning Mutagenesis and ELISA

Author(s):  
Tomohiro Tanaka ◽  
Teizo Asano ◽  
Masato Sano ◽  
Junko Takei ◽  
Hideki Hosono ◽  
...  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Phanthakarn Tit-oon ◽  
Kannan Tharakaraman ◽  
Charlermchai Artpradit ◽  
Abhinav Godavarthi ◽  
Pareenart Sungkeeree ◽  
...  

Abstract Nipah Virus (NiV) has been designated as a priority disease with an urgent need for therapeutic development by World Health Organization. The monoclonal antibody m102.4 binds to the immunodominant NiV receptor-binding glycoprotein (GP), and potently neutralizes NiV, indicating its potential as a therapeutic agent. Although the co-crystal structure of m102.3, an m102.4 derivative, in complex with the GP of the related Hendra Virus (HeV) has been solved, the structural interaction between m102.4 and NiV is uncharacterized. Herein, we used structure-guided alanine-scanning mutagenesis to map the functional epitope and paratope residues that govern the antigen–antibody interaction. Our results revealed that the binding of m102.4 is mediated predominantly by two residues in the HCDR3 region, which is unusually small for an antibody-antigen interaction. We performed computational docking to generate a structural model of m102.4-NiV interaction. Our model indicates that m102.4 targets the common hydrophobic central cavity and a hydrophilic rim on the GP, as observed for the m102.3-HeV co-crystal, albeit with Fv orientation differences. In summary, our study provides insight into the m102.4-NiV interaction, demonstrating that structure-guided alanine-scanning and computational modeling can serve as the starting point for additional antibody reengineering (e.g. affinity maturation) to generate potential therapeutic candidates.


Author(s):  
Tomohiro Tanaka ◽  
Teizo Asano ◽  
Masato Sano ◽  
Junko Takei ◽  
Hideki Hosono ◽  
...  

2011 ◽  
Author(s):  
Molly McCormley ◽  
Peter Cook ◽  
Madison Miketa ◽  
Colleen Reichmuth

2018 ◽  
Vol 44 (3) ◽  
pp. 293-298
Author(s):  
Fernando R. Elorriaga-Verplancken ◽  
Patricia Meneses ◽  
Abraham Cárdenas-Llerenas ◽  
Wayne Phillips ◽  
Abel de la Torre ◽  
...  

2006 ◽  
Vol 281 (42) ◽  
pp. 31832-31842
Author(s):  
Jeffrey Mercante ◽  
Kazushi Suzuki ◽  
Xiaodong Cheng ◽  
Paul Babitzke ◽  
Tony Romeo

2007 ◽  
Vol 122 (5) ◽  
pp. 2916 ◽  
Author(s):  
David Kastak ◽  
Colleen Reichmuth ◽  
Marla M. Holt ◽  
Jason Mulsow ◽  
Brandon L. Southall ◽  
...  

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