Preclinical development of humanized monoclonal antibodies against CD169 as a broad antiviral therapeutic strategy

Patricia Resa-Infante, Itziar Erkizia, Xabier Muniz-Trabudua, Federica Linty, Arthur E. H. Bentlage, Daniel Perez-Zsolt, Jordana Munoz-Basagoiti, Dalia Raich-Regue, Nuria Izquierdo-Useros, Theo Rispens, Gestur Vidarsson, Javier Martinez-Picado

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

New therapies to treat or prevent viral infections are essential, as recently observed during the COVID-19 pandemic. Here, we propose a therapeutic strategy based on monoclonal antibodies that block the specific interaction between the host receptor Siglec-1/CD169 and gangliosides embedded in the viral envelope. Antibodies are an excellent option for treating infectious diseases based on their high specificity, strong targeting affinity, and relatively low toxicity. Through a process of humanization, we optimized monoclonal antibodies to eliminate sequence liabilities and performed biophysical characterization. We demonstrated that they maintain their ability to block viral entry into myeloid cells. These molecular improvements during the discovery stage are key if we are to maximize efforts to develop new therapeutic strategies. Humanized monoclonal antibodies targeting CD169 provide new opportunities in the treatment of infections caused by ganglioside-containing enveloped viruses, which pose a constant threat to human health. In contrast with current neutralizing antibodies that bind antigens on the infectious particle, our antibodies can prevent several types of enveloped viruses interacting with host cells because they target the host CD169 protein, thus becoming a potential pan -antiviral therapy.
Original languageEnglish
Article number116726
Number of pages13
JournalBiomedicine and Pharmacotherapy
Volume175
DOIs
Publication statusPublished - Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Funding

PR-I was supported by grant 2017 BP 00121 from the Catalan Agency of Management of University and Research Grants. We are grateful to J. D\u00EDaz from the CMCiB for his constant help at the BSL3 facility. We thank Ninotska Derksen for assisting with the HP-SEC experiments. The authors also acknowledge the crowdfunding initiative #Yomecorono ( https://www.yomecorono.com ) and Foundation Dormeur for financial support to acquire the QuantStudio-5 real-time PCR system and an Eclipse Ts2RFL inverted research microscope. Some figures were created with BioRender.com. NI-U is supported by the Spanish Ministry of Science and Innovation (grant PID2020-117145RB-I00), EU HORIZON-HLTH-2021-CORONA-01 (grant 101046118), and by institutional funding from Pharma Mar and HIPRA. Research at the laboratory of JM-P is supported by the Spanish Ministry of Science, Innovation and Universities (grants PID2022-139271OB-I00, PID2019-109870RB-I00 and CB21/13/00063) and in part by Grifols. His laboratory has been funded by the NIH/NIAID (1 UM1 AI164561-01 and 1P01AI178376-01), EU HORIZON-HLTH-2021-DISEASE-04-07 (grants 101057100 and 101095606, European Union), Fundaci\u00F3 La Marat\u00F3 de TV3 (grant 202130-30-31-32, Spain), and Generalitat de Valencia (grant PROMETEO/2021/036, Spain). PR-I was supported by grant 2017 BP 00121 from the Catalan Agency of Management of University and Research Grants.XM-T was supported by the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund under agreement No. BES-2017\u2013082900.Research at the laboratory of JM-P is supported by the Spanish Ministry of Science, Innovation and Universities (grants PID2022\u2013139271OB-I00, PID2019\u2013109870RB-I00 and CB21/13/00063) and in part by Grifols. His laboratory has been funded by the NIH/NIAID (1 UM1 AI164561\u201301 and 1P01AI178376\u201301), EU HORIZON-HLTH-2021-DISEASE-04\u201307 (grants 101057100 and 101095606, European Union), Fundaci\u00F3 La Marat\u00F3 de TV3 (grant 202130\u201330\u201331\u201332, Spain), and Generalitat de Valencia (grant PROMETEO/2021/036, Spain).NI-U is supported by the Spanish Ministry of Science and Innovation (grant PID2020\u2013117145RB-I00), EU HORIZON-HLTH-2021-CORONA-01 (grant 101046118), and by institutional funding from Pharma Mar and HIPRA. XM-T was supported by the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund under agreement No. BES-2017-082900.

FundersFunder number
Catalan Agency of Management of University
Foundation Dormeur
Pharma Mar
National Institutes of Health
HIPRA
European Commission101057100, 101095606, 101046118, HORIZON-HLTH-2021-DISEASE-04-07, HORIZON-HLTH-2021-CORONA-01
European Commission
Ministerio de Ciencia e InnovaciónPID2020-117145RB-I00, 101046118
Ministerio de Ciencia e Innovación
National Institute of Allergy and Infectious Diseases1P01AI178376-01, 1 UM1 AI164561-01
National Institute of Allergy and Infectious Diseases
European Regional Development FundPID2019–109870RB-I00, CB21/13/00063, PID2022–139271OB-I00, BES-2017-082900
European Regional Development Fund
Generalitat ValencianaPROMETEO/2021/036
Generalitat Valenciana
Fundació la Marató de TV3202130-30-31-32
Fundació la Marató de TV3
Ministerio de Ciencia, Innovación y UniversidadesPID2019-109870RB-I00, CB21/13/00063, PID2022-139271OB-I00
Ministerio de Ciencia, Innovación y Universidades

    Keywords

    • Antibody therapy
    • Antivirals
    • Humanization
    • Methods
    • Monoclonal antibody

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