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Subclass-switched anti-Spike IgG3 oligoclonal cocktails strongly enhance Fc-mediated opsonization

Izadi, Arman (author)
Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Kvantitativ immunbiologi,Forskargrupper vid Lunds universitet,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Quantitative immunobiology,Lund University Research Groups
Hailu, Arsema (author)
Lund University,Lunds universitet,Kvantitativ immunbiologi,Forskargrupper vid Lunds universitet,Quantitative immunobiology,Lund University Research Groups
Godzwon, Magdalena (author)
Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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Wrighton, Sebastian (author)
Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Kvantitativ immunbiologi,Forskargrupper vid Lunds universitet,epIgG,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Quantitative immunobiology,Lund University Research Groups
Olofsson, Berit (author)
Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,epIgG,Forskargrupper vid Lunds universitet,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
Schmidt, Tobias (author)
Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Barnreumatologiskt forskningscentrum,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Center of Pediatric Rheumatology,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine
Söderlund Strand, Anna (author)
Lund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine,Skåne University Hospital
Elder, Elizabeth (author)
Swedish National Veterinary Institute
Appelberg, Sofia (author)
Public Health Agency of Sweden
Valsjö, Maria (author)
Scantox A/S
Larsson, Olivia (author)
Scantox A/S
Wendel-Hansen, Vidar (author)
Tanea Medical AB
Ohlin, Mats (author)
Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,SciLifeLab Site@Lund,Forskargrupper vid Lunds universitet,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,Lund University Research Groups
Bahnan, Wael (author)
Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Kvantitativ immunbiologi,Forskargrupper vid Lunds universitet,epIgG,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Quantitative immunobiology,Lund University Research Groups
Nordenfelt, Pontus (author)
Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Kvantitativ immunbiologi,Forskargrupper vid Lunds universitet,SEBRA Sepsis and Bacterial Resistance Alliance,epIgG,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LTH profilområde: Avancerade ljuskällor,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Quantitative immunobiology,Lund University Research Groups,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LTH Profile Area: Photon Science and Technology,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas,Skåne University Hospital
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 (creator_code:org_t)
2023
2023
English.
In: Proceedings of the National Academy of Sciences. - 1091-6490. ; 120:15
Related links:
http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Keyword

Antikroppar
SARS-COV-2
Fagocytos
Neutrofiler
COVID-19

Publication and Content Type

art (subject category)
ref (subject category)

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