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Omicron spike protein:a clue for viral entry and immune evasion

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3639-3640页

作者： G.M.N.Behrens A.Cossmann M.Hoffmann Department for Rheumatology and Immunology Hannover Medical SchoolHannoverGermany German Centre for Infection Research partner site Hannover-BraunschweigHannoverGermany CiiM Centre for Individualized Infection MedicineHannoverGermany Infection Biology Unit German Primate CenterGöttingen 37077Germany Faculty of Biology and Psychology Georg-August-University GöttingenGöttingenGermany

In a recent study in Science,Bowen et al.1 report that mutations in Omicron sublineage’s spike protein enhance ACE2 binding,impair fusogenicity,and dampen the neutralizing activity of antibodies after vaccination or infection.The data describe how Omicron and especially the BA.5 variant evade neutralizing antibody responses and argue for using mRNA booster vaccination to increase immunity.

关键词： ACE2 Bowen al.

Puerarin@Chitosan composite for infected bone repair through mimicking the bio-functions of antimicrobial peptides

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Bioactive Materials 2023年第3期21卷 520-530页

作者： Liping Ouyang Baohui Chen Xingdan Liu Donghui Wang Yang Li Yun Liao Kelvin W.K.Yeung Xuanyong Liu State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai200050China Hongqiao International Institute of edicine Shanghai Jiao Tong University School of MedicineShanghai200336China Cixi Center of Biomaterials Surface Engineering Ningbo315300China Department of Computational Biology for Individualised Medicine Centre for Individualised Infection Medicine(CiiM)&TWINCOREJoint Ventures Between the Helmholtz-Centre for Infection Research(HZI)and the Hannover Medical School(MHH)HannoverGermany Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma Guangdong Engineering Technology Research Center for Orthopaedic Trauma RepairDepartment of Orthopaedics and TraumatologyThe University of Hong Kong Shenzhen HospitalShenzhenChina

It is important to eliminate lipopolysaccharide(LPS)along with killing bacteria in periprosthetic joint infection(PJI)therapy for promoting bone repair due to its effect to regulate macrophages response.Although natural antimicrobial peptides(AMPs)offer a good solution,the unknown toxicity,high cost and exogenetic immune response hamper their applications in clinic.In this work,we fabricated a nanowire-like composite material,named P@C,by combining chitosan and puerarin via solid-phase reaction,which can finely mimic the bio-functions of AMPs.Chitosan,serving as the bacteria membrane puncture agent,and puerarin,serving as the LPS target agent,synergistically destroy the bacterial membrane structure and inhibit its recovery,thus endowing P@C with good antibacterial property.In addition,P@C possesses good osteoimmunomodulation due to its ability of LPS elimination and macrophage differentiation modulation.The in vivo results show that P@C can inhibit the LPS induced bone destruction in the Escherichia coli infected rat.P@C exhibits superior bone regeneration in Escherichia coli infected rat due to the comprehensive functions of its superior antibacterial property,and its ability of LPS elimination and immunomodulation.P@C can well mimic the functions of AMPs,which provides a novel and effective method for treating the PJI in clinic.

关键词： Osteoimmunomodulation Antibacterial Chitosan Puerarin Lipopolysaccharide

Efficient antibody evasion but reduced ACE2 binding by the emerging SARS-CoV-2 variant B.1.640.2

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Cellular & Molecular Immunology 2022年第9期19卷 1067-1069页

作者： Prerna Arora Amy Kempf Inga Nehlmeier Luise Graichen Sebastian Schulz Anne Cossmann Alexandra Dopfer-Jablonka Martin S.Winkler Hans-Martin Jäck Georg M.N.Behrens Stefan Pöhlmann Markus Hoffmann Infection Biology Unit German Primate CenterKellnerweg 437077GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073GöttingenGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergGlückstraße 691054ErlangenGermany Department for Rheumatology and Immunology Hannover Medical SchoolCarl-Neuberg-Straße 130625HannoverGermany German Centre for Infection Research(DZIF) Partner Site Hannover-BraunschweigHannoverGermany Centre for Individualised Infection Medicine(CiiM) HannoverGermany Department of Anesthesiology University of Göttingen Medical CenterGöttingenGeorg-August University of GöttingenRobert-Koch-Straße 4037075GöttingenGermany

The SARS-CoV-2 spike(S)protein engages ACE2 for cell entry,and the S protein/ACE2 interface is an important target for neutralizing antibodies.In the course of the COVID-19 pandemic,SARS-CoV-2 variants have emerged that harbor mutations in the S protein,which confer neutralization resistance and allow viral spread in immunologically nonnaive populations.The most prominent example is the highly mutated Omicron variant,which infects convalescent or vaccinated individuals with unprecedented efficiency[1,2].

关键词： ACE2 harbor neutral

Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks

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Signal Transduction and Targeted Therapy 2022年第1期7卷 243-257页

作者： Louisa Ruhl Isabell Pink Jenny F.Kiihne Kerstin Beushausen Jana Keil Stella Christoph Andrea Sauer Lennart Boblitz Julius Schmidt Sascha David Hans-Martin Jack Edith Roth Markus Cornberg Thomas F.Schulz Tobias Welte Marius M.Hoper Christine S.Falk Institute of Transplant Immunology MHHDHanoverGermany Department of Pneumology MHHDHanoverGermany Department of Intensive Care Medicine University of ZurichCHZurichSwitzerland Division of Molecular Immunology Internal Medicine IIINikolaus-Fiebiger-Center of Molecular MedicineFriedrich-Alexander University Erlangen-NurnbergDErlangenGermany Department of Gastroenterology Hepatology and Endocrinology MHHDHanoverGermany Center for Individualized Infection Medicine CiiM HanoverGermany lnstitute of Virology MHHDHanoverGermany German Center for Infection Research DZIFTTU-IICHMarburgGermany Excellence Cluster 2155 RESIST MHHHanoverGermany German Center for Lung Diseases DZL/BREATH MarburgGermany

The systemic processes involved in the manifestation of life・threatening COVID-19 and in disease recovery are still incompletely understood,despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection.To define hallmarks of severe COVID-19 in acute disease(n=58)and in disease recovery in con valesce nt patie nts(n=28)from Han nover Medical School,we used flow cytometry and proteomics data with unsupervised clustering analyses.In our observational study,we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury.ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies.The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19.Changes within this sign ature were associated with either disease progression or recovery.In summary,our data suggest that besides a strong inflammatory response,severe COVID-19 is driven by endothelial activation and barrier disruption,whereby recovery depends on the regeneration of the endothelial integrity.

关键词： cytokine networks signature

Profound neutralization evasion and augmented host cell entry are hallmarks of the fast-spreading SARS-CoV-2 lineage XBB.1.5

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Cellular & Molecular Immunology 2023年第4期20卷 419-422页

作者： Markus Hoffmann Prerna Arora Inga Nehlmeier Amy Kempf Anne Cossmann Sebastian R.Schulz Gema Morillas Ramos Luis A.Manthey Hans-Martin Jäck Georg M.N.Behrens Stefan Pöhlmann Infection Biology Unit German Primate CenterKellnerweg 437077 GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073 GöttingenGermany Department for Rheumatology and Immunology Hannover Medical SchoolCarl-Neuberg-Straße 130625 HannoverGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergGlückstraße 691054 ErlangenGermany German Centre for Infection Research(DZIF) partner site Hannover-BraunschweigCarl-Neuberg-Straße 130625 HannoverGermany Centre for Individualized Infection Medicine(CiiM) FeodorLynen-Straße730625 HannoverGermany

Since late 2022, the share of infections caused by the SARS-CoV2 lineage XBB.1.5 has gradually increased in the United States,resulting in XBB.1.5 becoming the dominating SARS-CoV-2lineage in the United States and a similar trend is likely to soontake place also in European countries. However, information onthe virological properties of XBB.1.5 is scarce. Here, weconducted an initial virological assessment of the SARS-CoV-2XBB.1.5 lineage.

关键词： becoming likely lineage

Host cell entry and neutralisation sensitivity of the SARS-CoV-2 XBB.1.16 lineage

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Cellular & Molecular Immunology 2023年第8期20卷 969-971页

作者： Inga Nehlmeier Amy Kempf Prerna Arora Anne Cossmann Alexandra Dopfer-Jablonka Metodi V.Stankov Sebastian R.Schulz Hans-Martin Jäck Georg M.N.Behrens Stefan Pöhlmann Markus Hoffmann Infection Biology Unit German Primate Center—Leibniz Institute for Primate ResearchKellnerweg 437077GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073GöttingenGermany Department of Rheumatology and Immunology Hannover Medical SchoolCarl-Neuberg-Straße 130625HannoverGermany German Centre for Infection Research(DZIF) Partner Site Hannover-BraunschweigCarl-Neuberg-Straße 130625HannoverGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergGlückstraße 691054ErlangenGermany Centre for Individualized Infection Medicine(CiiM) Feodor-Lynen-Straße 730625HannoverGermany

Despite previous circulation of the highly transmissible and antibody evasive BA.2.75, BQ.1, XBB.1 and XBB.1.5 lineages, the share of infections caused by the SARS-CoV-2 lineage XBB.1.16 has gradually increased in India in early 2023, resulting in XBB.1.16 being the dominating SARS-CoV-2 lineage in India today. Since a similar trend may also take place in other countries and information on the biological properties of the XBB.1.16 lineage is scarce, we conducted a rapid assessment of the SARS-CoV-2 XBB.1.16 lineage with respect to its ability to enter cells and evade neutralisation by antibodies.

关键词： lineage neutral spite

MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination

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Cellular & Molecular Immunology 2022年第2期19卷 234-244页

作者： Yeonsu Kim Xiaoyan Zheng Kathrin Eschke M.Zeeshan Chaudhry Federico Bertoglio Adriana Tomić Astrid Krmpotić Markus Hoffmann Yotam Bar-On Julia Boehme Dunja Bruder Thomas Ebensen Linda Brunotte Stephan Ludwig Martin Messerle Carlos Guzman Ofer Mandelboim Michael Hust Stefan Pöhlmann Stipan Jonjić LukaČičin-Šain Department of Viral Immunology Helmholtz Centre for Infection Research(HZI)BraunschweigGermany Department of Biotechnology Institut für BiochemieBiotechnologie und BioinformatikTechnischen Universität BraunschweigBraunschweigGermany Oxford Vaccine Group University of OxfordOxfordUK Center for Proteomics University of RijekaFaculty of MedicineRijekaCroatia Infection Biology Unit German Primate CenterGöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenGöttingenGermany Department of Immunology Rappaport Faculty of MedicineTechnion-Israel Institute of TechnologyHaifaIsrael Infection Immunology Institute for Medical Microbiology and Hospital HygieneHealth Campus ImmunologyInfectiology and InflammationOtto-von-Guericke-University MagdeburgMagdeburgGermanyImmune RegulationHelmholtz Centre for Infection ResearchBraunschweigGermany Department of Vaccinology and Applied Microbiology Helmholtz Centre for Infection ResearchBraunschweigGermany Institute of Virology Medical University MünsterMünsterGermany Institute of Virology Hannover Medical School(MHH)HannoverGermany German Centre for Infection Research(DZIF) Hannover-Braunschweig SiteHannoverGermany Centre for Individualized Infection medicine(CiiM) a joint venture of HZI and MHHHannoverGermany

Global pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality.There remains a medical need for vaccines against these pathogens.CMV(cytomegalovirus)is aβ-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific CD8+T cells are maintained for a lifetime.Hence,CMV has been proposed and investigated as a novel vaccine vector for expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens.We generated two recombinant murine CMV(MCMV)vaccine vectors expressing hemagglutinin(HA)of influenza A virus(MCMV^(HA))or the spike protein of severe acute respiratory syndrome coronavirus 2(MCMV^(S)).A single injection of MCMVs expressing either viral protein induced potent neutralizing antibody responses,which strengthened over time.Importantly,MCMV^(HA)-vaccinated mice were protected from illness following challenge with the influenza virus,and we excluded that this protection was due to the effects of memory T cells.Conclusively,we show here that MCMV vectors induce not only long-term cellular immunity but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.

关键词： Vaccine vector SARS-CoV-2 Influenza Cytomegalovirus humoral imunity