Afucosylated anti-EBOV antibody MIL77-3 engages sGP to elicit NK cytotoxicity
Zaire Ebolavirus (EBOV) is highly lethal and causes sporadic outbreaks. The passive administration of monoclonal antibodies (mAbs) represents a promising treatment regimen against EBOV. Mounting evidence has shown that the efficacy of a subset of therapeutic mAbs <i>in vivo</i> is intimately associated with its capacity to trigger NK activity, supporting glycomodification of Fc region of anti-EBOV mAbs as a putative strategy to enhance Fc-mediated immune effector function as well as protection <i>in vivo</i>. Our work here uncovers the potential harmful influence of this modification on host immune responses, especially for mAbs with cross-reactivity to secreted glycoproptein (sGP) (e.g., MIL77-3), and highlights it is necessary to evaluate the NK-stimulating activity of a fucosylated mAb engaged with sGP when a new candidate is developed.
Authors
- Xiaonan Wu (ORCID: https://orcid.org/0000-0002-0132-6980)
- Mianjing Wang
- Hang Zheng (ORCID: https://orcid.org/0000-0001-5143-8553)
- Guojiang Chen (ORCID: https://orcid.org/0009-0003-7289-0495)
- Min Zhang (ORCID: https://orcid.org/0000-0002-2001-7147)
- Weijin Huang (ORCID: https://orcid.org/0000-0002-4246-8889)
- Junjuan Feng (ORCID: https://orcid.org/0000-0002-4823-0863)
- Yuting Zhang (ORCID: https://orcid.org/0000-0003-4204-9091)
- Xinying Li (ORCID: https://orcid.org/0000-0001-8462-8919)
- Chunxia Qiao (ORCID: https://orcid.org/0000-0003-3789-8806)
- Yuanqiang Zheng (ORCID: https://orcid.org/0000-0002-8914-2851)
- Longlong Luo (ORCID: https://orcid.org/0000-0002-8307-6478)
- Yi Wang (ORCID: https://orcid.org/0000-0003-2454-5702)
- He Xiao
- Youchun Wang
- Jiannan Feng (ORCID: https://orcid.org/0000-0002-9322-549X)
- Haiyan Wu
- Jing Wang (ORCID: https://orcid.org/0000-0001-7431-8925)
Institutions
- Henan University (CN)
- Chinese PLA General Hospital (CN)
- National Institutes for Food and Drug Control (CN)
- Institute of Pharmacology (CZ)
- Inner Mongolia Medical University (CN)
Publication Details
- Journal
- Journal of Virology
- Published
- 2024-08-20
- DOI
- https://doi.org/10.1128/jvi.00685-24
- Citations
- 2
- Primary Topic
- Viral Infections and Outbreaks Research
- Type
- article
- Field-Weighted Citation Impact
- 0.78
Funders
- National Natural Science Foundation of China