Light Chain Isotype and Antibody-Specificity Impact on Virus Neutralization

Therapeutic antibodies with lambda light chains (λ-Abs) are underrepresented compared to kappa light chains (κ-Abs). Here, we evaluated two SARS-CoV-2-specific monoclonal antibodies (mAbs) that exhibit high (P5C3) and low (H4) antigen binding as κ and λ variants. mAbs expressed in glycoengineered &l...

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Hauptverfasser: Lin Sun, Roman Palt, Georg Schütz, Esther Föderl-Höbenreich, Laura Brod, Antonia Hermle, Anja Lux, Herta Steinkellner, Somanath Kallolimath
Format: Artikel
Sprache:Englisch
Veröffentlicht: MDPI AG 2025-06-01
Schriftenreihe:Antibodies
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Online-Zugang:https://www.mdpi.com/2073-4468/14/2/50
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Zusammenfassung:Therapeutic antibodies with lambda light chains (λ-Abs) are underrepresented compared to kappa light chains (κ-Abs). Here, we evaluated two SARS-CoV-2-specific monoclonal antibodies (mAbs) that exhibit high (P5C3) and low (H4) antigen binding as κ and λ variants. mAbs expressed in glycoengineered <i>Nicotiana benthamiana</i> did not show differences in expression levels, glycosylation, and antigen binding, while κ-Abs exhibited slightly increased thermodynamic stability over λ-Abs. SARS-CoV-2 neutralization and IgG-FcγR immune complex studies revealed increased activities of H4 IgG1κ compared to H4 IgG1λ, with no differences observed between P5C3 variants. Our results indicate that constant light chain variability and Ab specificity contribute to Ab features, a fact that should be considered in engineering therapeutics.
ISSN:2073-4468