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Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
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Light Chain Isotype and Antibody-Specificity Impact on Virus Neutralization
Lin Sun1, Roman Palt1, Georg Schütz2
1Department of Biotechnology and Food Sciences, Institute of Plant Biotechnology and Cell Biology, BOKU University, Muthgasse 18, 1190 Vienna, Austria.
Antibodies (Basel, Switzerland)
|June 25, 2025
Summary
Therapeutic antibodies using lambda light chains (λ-Abs) are less common than kappa light chains (κ-Abs). This study found that kappa variants showed slightly higher stability and, for one antibody, increased activity against SARS-CoV-2 compared to lambda variants.
Area of Science:
- Biotechnology
- Immunology
- Molecular Biology
Background:
- Therapeutic antibodies are crucial biologics, yet lambda light chain antibodies (λ-Abs) are underrepresented compared to kappa light chain antibodies (κ-Abs).
- Understanding the impact of light chain isotypes on antibody function is essential for optimizing therapeutic antibody development.
Purpose of the Study:
- To compare the expression, glycosylation, stability, antigen binding, and functional activity of SARS-CoV-2-specific monoclonal antibodies (mAbs) with kappa (κ) versus lambda (λ) light chains.
- To investigate the influence of light chain isotypes on antibody effector functions, including neutralization and immune complex formation.
Main Methods:
- Expression of two SARS-CoV-2 mAbs (P5C3 and H4) with high and low antigen binding, respectively, as κ and λ variants in glycoengineered *Nicotiana benthamiana*.
- Characterization of mAbs for expression levels, glycosylation, thermodynamic stability, and antigen binding affinity.
- Assessment of SARS-CoV-2 neutralization activity and IgG-FcγR immune complex formation for both κ and λ variants.
Main Results:
- No significant differences in expression levels, glycosylation, or antigen binding were observed between κ and λ variants of both mAbs.
- Kappa light chain antibodies (κ-Abs) demonstrated slightly increased thermodynamic stability compared to lambda light chain antibodies (λ-Abs).
- The H4 κ antibody variant exhibited enhanced SARS-CoV-2 neutralization and IgG-FcγR immune complex activity compared to its H4 λ counterpart, while P5C3 variants showed no difference.
Conclusions:
- Constant light chain isotype influences antibody stability and functional activity, particularly for antibodies with lower antigen binding affinity.
- Both light chain variability and antibody specificity are critical factors to consider when engineering therapeutic antibodies.
- These findings highlight the importance of evaluating both kappa and lambda light chains in the development of novel antibody therapeutics.
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