Optimization of a Human Anti-polio Monoclonal Antibody as a Potential Therapeutic Modality
- 1PATH
Abstract
Background. Vaccines have been an essential tool in bringing the world close to polio eradication, with over 99.9 percent of the global population free of poliovirus. No antiviral drugs or monoclonal antibody products, however, are currently licensed for treatment of polio. We previously isolated a human monoclonal antibody (9H2) with potent neutralizing activity against all three poliovirus serotypes. To advance 9H2 as a therapeutic candidate, we optimized its sequence to extend serum half-life and improve manufacturability. Methods. A Multi-Attribute Method under stress conditions identified post-translational modification sites, and Abacus (Trademark) ranked sequence liabilities. Six amino acid substitutions were introduced into the variable regions, generating 23 combinatorial variants. Codon-optimized genes were synthesized and engineered into a human immunoglobulin G1 backbone containing crystallizable fragment (Fc) mutations (M428L/N434S) to extend serum half-life. Constructs were transfected into CHO K1 cells to generate stable pools in 24 well plates. Protein A purified antibodies were characterized using biophysical assays and an in vitro poliovirus neutralization assay. Results. All variants retained high in vitro neutralizing activity against poliovirus. A lead candidate was selected based on integrated assessment of biophysical properties across eight assays and expression yield. Conclusions. Structure-guided engineering and experimental evaluation enabled optimization of the 9H2 antibody sequence and identification of a lead candidate suitable for clinical manufacturing as a potential anti-poliovirus immunotherapeutic agent.
Related
- Targeting Integrins in Triple Negative Breast Cancer: Therapeutic Potential of Monoclonal Antibodies, PARP Inhibitors, Synthetic Peptides, and Aptamers
- Genotypic infection endpoint analysis to understand efficacy and escape potential of the malaria monoclonal antibody CIS43LS
- Treatment Optimization with Add-On Kampo Therapy in Highly Refractory Migraine Patients with Inadequate Response or Re-Worsening During CGRP Monoclonal Antibody Therapy: A Real-World Treatment Episode Analysis
- MuSK agonistic antibody has therapeutic potential for MuSK antibody-positive myasthenia gravis
- A neutralizing monoclonal antibody targeting species B adenoviruses largely mimics the DSG2 receptor engagement mechanism
BibTeX
@misc{lee2026optimization,
title = {{Optimization of a Human Anti-polio Monoclonal Antibody as a Potential Therapeutic Modality}},
author = {S.-M. Lee and C. Siska and I. D'Angelo and D. Kouiavskaia and K. Mahmood},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.20.753044},
url = {https://www.biorxiv.org/content/10.64898/2026.09.20.753044v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Optimization of a Human Anti-polio Monoclonal Antibody as a Potential Therapeutic Modality
AU - S.-M. Lee
AU - C. Siska
AU - I. D'Angelo
AU - D. Kouiavskaia
AU - K. Mahmood
PY - 2026
DA - 2026/09/20
PB - bioRxiv
DO - 10.64898/2026.09.20.753044
UR - https://www.biorxiv.org/content/10.64898/2026.09.20.753044v1
AB - Background. Vaccines have been an essential tool in bringing the world close to polio eradication, with over 99.9 percent of the global population free of poliovirus. No antiviral drugs or monoclonal antibody products, however, are currently licensed for treatment of polio. We previously isolated a human monoclonal antibody (9H2) with potent neutralizing activity against all three poliovirus serotypes. To advance 9H2 as a therapeutic candidate, we optimized its sequence to extend serum half-life and improve manufacturability. Methods. A Multi-Attribute Method under stress conditions identified post-translational modification sites, and Abacus (Trademark) ranked sequence liabilities. Six amino acid substitutions were introduced into the variable regions, generating 23 combinatorial variants. Codon-optimized genes were synthesized and engineered into a human immunoglobulin G1 backbone containing crystallizable fragment (Fc) mutations (M428L/N434S) to extend serum half-life. Constructs were transfected into CHO K1 cells to generate stable pools in 24 well plates. Protein A purified antibodies were characterized using biophysical assays and an in vitro poliovirus neutralization assay. Results. All variants retained high in vitro neutralizing activity against poliovirus. A lead candidate was selected based on integrated assessment of biophysical properties across eight assays and expression yield. Conclusions. Structure-guided engineering and experimental evaluation enabled optimization of the 9H2 antibody sequence and identification of a lead candidate suitable for clinical manufacturing as a potential anti-poliovirus immunotherapeutic agent.
ER -