Subclass-switched anti-Spike IgG3 oligoclonal cocktails strongly enhance Fc-mediated opsonization
(2023) In Proceedings of the National Academy of Sciences 120(15).- Abstract
- Antibodies play a central role in the immune defense against SARS-CoV-2. Emerging evidence has shown that nonneutralizing antibodies are important for immune defense through Fc-mediated effector functions. Antibody subclass is known to affect downstream Fc function. However, whether the antibody subclass plays a role in anti-SARS-CoV-2 immunity remains unclear. Here, we subclass-switched eight human IgG1 anti-spike monoclonal antibodies (mAbs) to the IgG3 subclass by exchanging their constant domains. The IgG3 mAbs exhibited altered avidities to the spike protein and more potent Fc-mediated phagocytosis and complement activation than their IgG1 counterparts. Moreover, combining mAbs into oligoclonal cocktails led to enhanced Fc- and... (More)
- Antibodies play a central role in the immune defense against SARS-CoV-2. Emerging evidence has shown that nonneutralizing antibodies are important for immune defense through Fc-mediated effector functions. Antibody subclass is known to affect downstream Fc function. However, whether the antibody subclass plays a role in anti-SARS-CoV-2 immunity remains unclear. Here, we subclass-switched eight human IgG1 anti-spike monoclonal antibodies (mAbs) to the IgG3 subclass by exchanging their constant domains. The IgG3 mAbs exhibited altered avidities to the spike protein and more potent Fc-mediated phagocytosis and complement activation than their IgG1 counterparts. Moreover, combining mAbs into oligoclonal cocktails led to enhanced Fc- and complement receptor-mediated phagocytosis, superior to even the most potent single IgG3 mAb when compared at equivalent concentrations. Finally, in an in vivo model, we show that opsonic mAbs of both subclasses can be protective against a SARS-CoV-2 infection, despite the antibodies being nonneutralizing. Our results suggest that opsonic IgG3 oligoclonal cocktails are a promising idea to explore for therapy against SARS-CoV-2, its emerging variants, and potentially other viruses. (Less)
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https://lup.lub.lu.se/record/8990ecff-de85-4af9-a531-8eae11915524
- author
- organization
-
- Quantitative immunobiology (research group)
- Infection Medicine (BMC)
- Department of Immunotechnology
- epIgG (research group)
- Center of Pediatric Rheumatology (research group)
- Paediatrics (Lund)
- WCMM-Wallenberg Centre for Molecular Medicine
- Division of Medical Microbiology
- SciLifeLab Site@Lund (research group)
- LU Profile Area: Light and Materials
- LTH Profile Area: Nanoscience and Semiconductor Technology
- NanoLund: Centre for Nanoscience
- LTH Profile Area: Photon Science and Technology
- SEBRA Sepsis and Bacterial Resistance Alliance (research group)
- publishing date
- 2023-04-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Antikroppar, SARS-COV-2, Fagocytos, Neutrofiler, COVID-19
- in
- Proceedings of the National Academy of Sciences
- volume
- 120
- issue
- 15
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:37011197
- scopus:85151658285
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.2217590120
- project
- Functional Impact of Immunoglobulin G subclass in Bacterial and viral Infections
- language
- English
- LU publication?
- yes
- id
- 8990ecff-de85-4af9-a531-8eae11915524
- date added to LUP
- 2023-04-03 22:41:33
- date last changed
- 2024-05-16 09:18:40
@article{8990ecff-de85-4af9-a531-8eae11915524, abstract = {{Antibodies play a central role in the immune defense against SARS-CoV-2. Emerging evidence has shown that nonneutralizing antibodies are important for immune defense through Fc-mediated effector functions. Antibody subclass is known to affect downstream Fc function. However, whether the antibody subclass plays a role in anti-SARS-CoV-2 immunity remains unclear. Here, we subclass-switched eight human IgG1 anti-spike monoclonal antibodies (mAbs) to the IgG3 subclass by exchanging their constant domains. The IgG3 mAbs exhibited altered avidities to the spike protein and more potent Fc-mediated phagocytosis and complement activation than their IgG1 counterparts. Moreover, combining mAbs into oligoclonal cocktails led to enhanced Fc- and complement receptor-mediated phagocytosis, superior to even the most potent single IgG3 mAb when compared at equivalent concentrations. Finally, in an in vivo model, we show that opsonic mAbs of both subclasses can be protective against a SARS-CoV-2 infection, despite the antibodies being nonneutralizing. Our results suggest that opsonic IgG3 oligoclonal cocktails are a promising idea to explore for therapy against SARS-CoV-2, its emerging variants, and potentially other viruses.}}, author = {{Izadi, Arman and Hailu, Arsema and Godzwon, Magdalena and Wrighton, Sebastian and Olofsson, Berit and Schmidt, Tobias and Söderlund Strand, Anna and Elder, Elizabeth and Appelberg, Sofia and Valsjö, Maria and Larsson, Olivia and Wendel-Hansen, Vidar and Ohlin, Mats and Bahnan, Wael and Nordenfelt, Pontus}}, issn = {{1091-6490}}, keywords = {{Antikroppar; SARS-COV-2; Fagocytos; Neutrofiler; COVID-19}}, language = {{eng}}, month = {{04}}, number = {{15}}, publisher = {{National Academy of Sciences}}, series = {{Proceedings of the National Academy of Sciences}}, title = {{Subclass-switched anti-Spike IgG3 oligoclonal cocktails strongly enhance Fc-mediated opsonization}}, url = {{http://dx.doi.org/10.1073/pnas.2217590120}}, doi = {{10.1073/pnas.2217590120}}, volume = {{120}}, year = {{2023}}, }