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SHR Neuro Cancer Cardio Lipid Metab Microb
Chromikova, V; Mader, A; Hofbauer, S; Göbl, C; Madl, T; Gach, JS; Bauernfried, S; Furtmüller, PG; Forthal, DN; Mach, L; Obinger, C; Kunert, R.
Introduction of germline residues improves the stability of anti-HIV mAb 2G12-IgM.
Biochim Biophys Acta. 2015; 1854(10 Pt A):1536-1544
Doi: 10.1016/j.bbapap.2015.02.018
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- Co-authors Med Uni Graz
- Madl Tobias
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- Abstract:
- Immunoglobulins M (IgMs) are gaining increasing attention as biopharmaceuticals since their multivalent mode of binding can give rise to high avidity. Furthermore, IgMs are potent activators of the complement system. However, they are frequently difficult to express recombinantly and can suffer from low conformational stability. Here, the broadly neutralizing anti-HIV-1 antibody 2G12 was class-switched to IgM and then further engineered by introduction of 17 germline residues. The impact of these changes on the structure and conformational stability of the antibody was then assessed using a range of biophysical techniques. We also investigated the effects of the class switch and germline substitutions on the ligand-binding properties of 2G12 and its capacity for HIV-1 neutralization. Our results demonstrate that the introduced germline residues improve the conformational and thermal stability of 2G12-IgM without altering its overall shape and ligand-binding properties. Interestingly, the engineered protein was found to exhibit much lower neutralization potency than its wild-type counterpart, indicating that potent antigen recognition is not solely responsible for IgM-mediated HIV-1 inactivation. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Substitution -
- Animals -
- Antibodies, Monoclonal - biosynthesis
- Antibodies, Monoclonal - chemistry
- Antibodies, Monoclonal - immunology
- Antibodies, Monoclonal - pharmacology
- Base Sequence -
- CHO Cells -
- Cricetulus -
- Gene Expression -
- HEK293 Cells -
- HIV Antibodies - biosynthesis
- HIV Antibodies - chemistry
- HIV Antibodies - immunology
- HIV Antibodies - pharmacology
- HIV Envelope Protein gp120 - antagonists & inhibitors
- HIV Envelope Protein gp120 - chemistry
- HIV Envelope Protein gp120 - immunology
- HIV-1 - drug effects
- HIV-1 - growth & development
- Humans -
- Immunoglobulin Class Switching - genetics
- Immunoglobulin M - biosynthesis
- Immunoglobulin M - chemistry
- Immunoglobulin M - immunology
- Immunoglobulin M - pharmacology
- Molecular Sequence Data -
- Mutation -
- Neutralization Tests -
- Protein Conformation -
- Protein Engineering -
- Protein Stability -
- Recombinant Proteins - biosynthesis
- Recombinant Proteins - chemistry
- Recombinant Proteins - immunology
- Recombinant Proteins - pharmacology
- Sequence Alignment -
- Structure-Activity Relationship -
- Find related publications in this database (Keywords)
- Antibody engineering
- Germline
- HIV
- IgM
- Protein stability