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The hinge-engineere...
The hinge-engineered IgG1-IgG3 hybrid subclass IgGh47 potently enhances Fc-mediated function of anti-streptococcal and SARS-CoV-2 antibodies
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- Izadi, Arman (författare)
- Lund University,Lunds universitet,Kvantitativ immunbiologi,Forskargrupper vid Lunds universitet,Quantitative immunobiology,Lund University Research Groups,Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Karami, Yasaman (författare)
- University of Lorraine,Univ Lorraine, CNRS, Inria, LORIA, F-54000 Nancy, France; Univ Paris Cite, Inst Pasteur, Dept Struct Biol & Chem, Struct Bioinformat Unit, CNRS UMR3528, F-75015 Paris, France
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- Bratanis, Eleni (författare)
- Lund University,Lunds universitet,epIgG,Forskargrupper vid Lunds universitet,Lund University Research Groups,Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Wrighton, Sebastian (författare)
- Lund University,Lunds universitet,Kvantitativ immunbiologi,Forskargrupper vid Lunds universitet,epIgG,Quantitative immunobiology,Lund University Research Groups,Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Khakzad, Hamed (författare)
- University of Lorraine,Univ Lorraine, CNRS, Inria, LORIA, F-54000 Nancy, France
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- Nyblom, Maria (författare)
- Lund University,Lund Univ, Dept Biol, Lund, Sweden; Lund Univ, Lund Prot Prod Platform LP3, Lund, Sweden
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- Olofsson, Berit (författare)
- Lund University,Lunds universitet,Kvantitativ immunbiologi,Forskargrupper vid Lunds universitet,epIgG,Quantitative immunobiology,Lund University Research Groups,Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Happonen, Lotta (författare)
- Lund University,Lunds universitet,BioMS,Forskargrupper vid Lunds universitet,Strukturell infektionsmedicin,Lund University Research Groups,Structural Infection Medicine (STRIME),Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Tang, Di (författare)
- Lund University,Lunds universitet,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,Lund University Research Groups,Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Sundwall, Martin (författare)
- Lund University,Lunds universitet,Kvantitativ immunbiologi,Forskargrupper vid Lunds universitet,Quantitative immunobiology,Lund University Research Groups,Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Godzwon, Magdalena (författare)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,LTH profilområde: Teknik för hälsa,LTH profilområden,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LTH Profile Area: Engineering Health,LTH Profile areas,Faculty of Engineering, LTH,Lund Univ, Dept Immunotechnol, Lund, Sweden; Lund Univ, SciLifeLab Drug Discovery & Dev Platform, Lund, Sweden
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- Chao, Yashuan (författare)
- Lund University,Lunds universitet,Experimentell infektionsmedicin, Malmö,Forskargrupper vid Lunds universitet,Immunmodulerande effekter av blodplättar vid inflammation och infektion,Experimental Infection Medicine, Malmö,Lund University Research Groups,Immunomodulatory effects of platelets during inflammation and infection,Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Gomez Toledo, Alejandro (författare)
- Lund University,Lunds universitet,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,Lund University Research Groups,Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Schmidt, Tobias (författare)
- Lund University,Lunds universitet,Barnreumatologiskt forskningscentrum,Forskargrupper vid Lunds universitet,Center of Pediatric Rheumatology,Lund University Research Groups,Lund Univ, Fac Med, Dept Clin Sci Lund, Div Pediat, Lund, Sweden
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- Ohlin, Mats (författare)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,LTH profilområde: Teknik för hälsa,LTH profilområden,LU-ATMP: Lunds universitets centrum för avancerade terapier,Medicinska fakulteten,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments,LTH Profile Area: Engineering Health,LTH Profile areas,Faculty of Engineering, LTH,LU-ATMP: Lund University Advanced Therapy Medicinal Products,Faculty of Medicine,Lund Univ, Dept Immunotechnol, Lund, Sweden; Lund Univ, SciLifeLab Drug Discovery & Dev Platform, Lund, Sweden
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- Nilges, Michael (författare)
- Pasteur Institute,Univ Paris Cite, Inst Pasteur, Dept Struct Biol & Chem, Struct Bioinformat Unit, CNRS UMR3528, F-75015 Paris, France
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- Malmström, Johan (författare)
- Lund University,Lunds universitet,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,SEBRA Sepsis and Bacterial Resistance Alliance,epIgG,BioMS,LTH profilområde: Teknik för hälsa,LTH profilområden,Lunds Tekniska Högskola,Lund University Research Groups,LTH Profile Area: Engineering Health,LTH Profile areas,Faculty of Engineering, LTH,Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Bahnan, Wael (författare)
- Lund University,Lunds universitet,Kvantitativ immunbiologi,Forskargrupper vid Lunds universitet,epIgG,Quantitative immunobiology,Lund University Research Groups,Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Shannon, Oonagh (författare)
- Malmö universitet,Malmö University,Lund University,Lunds universitet,Immunmodulerande effekter av blodplättar vid inflammation och infektion,Forskargrupper vid Lunds universitet,SEBRA Sepsis and Bacterial Resistance Alliance,epIgG,Immunomodulatory effects of platelets during inflammation and infection,Lund University Research Groups,Odontologiska fakulteten (OD),Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Malmström, Lars (författare)
- Lund University,Lunds universitet,epIgG,Forskargrupper vid Lunds universitet,Lund University Research Groups,Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden
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- Nordenfelt, Pontus (författare)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,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,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,Lund Univ, Fac Med, Dept Clin Sci Lund, Infect Med, Lund, Sweden; Lund Univ, Skåne Univ Hosp Lund, Dept Lab Med, Clin Microbiol, Lund, Sweden
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(creator_code:org_t)
- Springer Nature, 2024
- 2024
- Engelska.
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15, s. 1-22
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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https://mau.diva-por... (primary) (Raw object)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Streptococcus pyogenes can cause invasive disease with high mortality despite adequate antibiotic treatments. To address this unmet need, we have previously generated an opsonic IgG1 monoclonal antibody, Ab25, targeting the bacterial M protein. Here, we engineer the IgG2-4 subclasses of Ab25. Despite having reduced binding, the IgG3 version promotes stronger phagocytosis of bacteria. Using atomic simulations, we show that IgG3’s Fc tail has extensive movement in 3D space due to its extended hinge region, possibly facilitating interactions with immune cells. We replaced the hinge of IgG1 with four different IgG3-hinge segment subclasses, IgGhxx. Hinge-engineering does not diminish binding as with IgG3 but enhances opsonic function, where a 47 amino acid hinge is comparable to IgG3 in function. IgGh47 shows improved protection against S. pyogenes in a systemic infection mouse model, suggesting that IgGh47 has promise as a preclinical therapeutic candidate. Importantly, the enhanced opsonic function of IgGh47 is generalizable to diverse S. pyogenes strains from clinical isolates. We generated IgGh47 versions of anti-SARS-CoV-2 mAbs to broaden the biological applicability, and these also exhibit strongly enhanced opsonic function compared to the IgG1 subclass. The improved function of the IgGh47 subclass in two distant biological systems provides new insights into antibody function.
Ämnesord
- 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)
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Izadi, Arman
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Karami, Yasaman
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Bratanis, Eleni
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Wrighton, Sebast ...
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Khakzad, Hamed
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Nyblom, Maria
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visa fler...
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Olofsson, Berit
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Happonen, Lotta
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Tang, Di
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Sundwall, Martin
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Godzwon, Magdale ...
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Chao, Yashuan
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Gomez Toledo, Al ...
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Schmidt, Tobias
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Ohlin, Mats
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Nilges, Michael
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Malmström, Johan
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Bahnan, Wael
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Shannon, Oonagh
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Malmström, Lars
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Nordenfelt, Pont ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Immunologi inom ...
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Nature Communica ...
- Av lärosätet
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Lunds universitet
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Malmö universitet