SARS-CoV-2: phenotype, genotype, and characterization of different variants

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: June 17, 2022

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of disease 2019 (COVID-19), a major international public health concern. Because very similar amino acid sequences seven domain names, SARS-CoV-2 belongs to Coronavirinae subfamily family Coronaviridae, order Nidovirales, and realm Riboviria, placed in exceptional clusters, but categorized as SARS-like species. As RNA virus with longest genome, Coronaviridae genome consists single strand positive (25–32 kb length). Four structural proteins this include spike (S), membrane (M), envelope (E), nucleocapsid (N) protein, all which are encoded within 3′ end genome. By engaging its receptor, angiotensin-converting enzyme (ACE2), infects host cells. According most recent epidemiological data, illness spread globally, several genetic variations appeared quickly, World Health Organization (WHO) naming 11 them. Among these, subtypes have received attention. Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron (B.1.617.2) now designated concern (VOC) (B.1.1.529). Lambda (C.37) Mu interest (VOI) (B.1.621). The remaining six either being monitored or no longer considered threat. On basis studies done so far, antiviral drugs, antibiotics, glucocorticoids, recombinant intravenous immunoglobulin, plasma therapy, IFN-α2b been used treat patients. Moreover, full vaccination associated lower infection helps prevent transmission, risk cannot be eliminated completely vaccinated people.

Language: Английский

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mRNA: Vaccine or Gene Therapy? The Safety Regulatory Issues

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10514 - 10514

Published: June 22, 2023

COVID-19 vaccines were developed and approved rapidly in response to the urgency created by pandemic. No specific regulations existed at time they marketed. The regulatory agencies therefore adapted them as a matter of urgency. Now that pandemic emergency has passed, it is consider safety issues associated with this rapid approval. mode action mRNA should classify gene therapy products (GTPs), but have been excluded agencies. Some tests undergone produced non-compliant results terms purity, quality batch homogeneity. wide persistent biodistribution mRNAs their protein products, incompletely studied due classification vaccines, raises issues. Post-marketing studies shown passes into breast milk could adverse effects on breast-fed babies. Long-term expression, integration genome, transmission germline, passage sperm, embryo/fetal perinatal toxicity, genotoxicity tumorigenicity be light events reported pharmacovigilance databases. potential horizontal (i.e., shedding) also assessed. In-depth vaccinovigilance carried out. We would expect these controls required for future outside context

Language: Английский

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Endothelial Dysfunction in COVID-19: Potential Mechanisms and Possible Therapeutic Options

Life, Journal Year: 2022, Volume and Issue: 12(10), P. 1605 - 1605

Published: Oct. 14, 2022

SARS-CoV-2, a novel coronavirus found in Wuhan (China) at the end of 2019, is etiological agent current pandemic that heterogeneous disease, named disease 2019 (COVID-19). SARS-CoV-2 affects primarily lungs, but it can induce multi-organ involvement such as acute myocardial injury, myocarditis, thromboembolic eventsandrenal failure. Hypertension, chronic kidney diabetes mellitus and obesity increase risk severe complications COVID-19. There no certain explanation for this systemic COVID-19 involvement, could be related to endothelial dysfunction, due direct (endothelial cells are infected by virus) indirect damage (systemic inflammation) factors. Angiotensin-converting enzyme 2 (ACE2), expressed human endothelium, has fundamental role respiratory syndrome (SARS-CoV-2) infection. In fact, ACE2 used receptor leading downregulation these receptors on cells; once inside, virus reduces integrity tissue, with exposure prothrombotic molecules, platelet adhesion, activation coagulation cascades and, consequently, vascular damage. Systemic microangiopathy thromboembolism lead failure an elevated death. Considering crucial immunological response developing form COVID-19, review, we will attempt clarify underlying pathophysiological mechanisms.

Language: Английский

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A perspective on SARS-CoV-2 virus-like particles vaccines

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 115, P. 109650 - 109650

Published: Jan. 11, 2023

Language: Английский

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Safety and immunogenicity of a protein subunit COVID-19 vaccine (ZF2001) in healthy children and adolescents aged 3–17 years in China: a randomised, double-blind, placebo-controlled, phase 1 trial and an open-label, non-randomised, non-inferiority, phase 2 trial

The Lancet Child & Adolescent Health, Journal Year: 2023, Volume and Issue: 7(4), P. 269 - 279

Published: Feb. 17, 2023

Language: Английский

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Molecular aspects of Omicron, vaccine development, and recombinant strain XE: A review

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 94(10), P. 4628 - 4643

Published: June 16, 2022

The global pandemic of COVID-19 began in December 2019 and is still continuing. past 2 years have seen the emergence several variants that were more vicious than each other. Omicron (B.1.1.529) proved to be a huge epidemiological concern as rate infection this particular strain was enormous. identified South Africa on November 24, 2021 classified "Variant Concern" 26, 2021. variant possessed mutations key RBD region, S thereby increasing affinity ACE2 for better transmission virus. Antibody resistance found it able reduce vaccine efficiency vaccines. need booster brought forth due prevalence and, subsequently, led targeted research development variant-specific vaccines dosage. This review discusses broadly genomic characters features along with its specific mutations, evolution, antibody resistance, evasion, utilization CRISPR-Cas12a assay detection, T-cell immunity elicited by against Omicron, strategies decrease also XE recombinant infectivity BA.2 subvariant Omicron.

Language: Английский

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Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

Vaccines, Journal Year: 2023, Volume and Issue: 11(2), P. 314 - 314

Published: Jan. 31, 2023

This paper presents a novel approach for improving the efficacy of COVID-19 vaccines against emergent SARS-CoV-2 variants. We have evaluated immunogenicity unadjuvanted wild-type (WU S1-RS09cg) and variant-specific (Delta S1-RS09cg OM S1 subunit protein delivered either as monovalent or trivalent antigen in BALB/c mice. Our results show that induced broader humoral response with more coverage antigenically distinct variants, especially when compared to Omicron-specific S1. was also found increased equivalent ACE2 binding inhibition, IgG endpoint titer at early timepoints, spike variants Wuhan, Delta, Omicron demonstrate utility provide insights into impact vaccine approaches on immune current variant landscape. Particularly, our study provides insight effects further increasing valency currently approved vaccines, promising protection curtail emerging viral

Language: Английский

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Epidemiology of bacterial respiratory tract infections during the pre-pandemic, COVID-19 pandemic and post-pandemic era: A retrospective study of hospitalized adults in northern Greece between 2018 and 2023

Diagnostic Microbiology and Infectious Disease, Journal Year: 2025, Volume and Issue: 111(3), P. 116710 - 116710

Published: Jan. 31, 2025

Language: Английский

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Fractionation of sulfated galactan from the red alga Botryocladia occidentalis separates its anticoagulant and anti-SARS-CoV-2 properties

Journal of Biological Chemistry, Journal Year: 2022, Volume and Issue: 298(5), P. 101856 - 101856

Published: March 23, 2022

Sulfation pattern and molecular weight (MW) play a key role in the biological actions of sulfated glycans. Besides anticoagulant effects, certain glycans can also exhibit anti-SARS-CoV-2 properties. To develop more selective antiviral carbohydrate, an efficient strategy to separate these two is required. In this work, low MW fractions derived from red alga Botryocladia occidentalis galactan (BoSG) were generated, structurally characterized, tested for activity against SARS-CoV-2 blood coagulation. The lowest fraction was found be primarily composed octasaccharides monosulfated monosaccharides. Unlike heparin or native BoSG, we that hydrolyzed BoSG products had weak activities as seen by aPTT inhibitory assays using purified cofactors. contrast, lower BoSG-derivatives retained spike (S)-protein pseudotyped lentivirus vector HEK-293T-hACE2 cells monitored GFP. Surface plasmon resonance confirmed longer chains are necessary interact with coagulation cofactors but not required interactions S-protein variants. We observed distinct affinities derivatives S-proteins different strains, including WT, N501Y (Alpha), K417T/E484K/N501Y (Gamma), L542R (Delta) mutants, stronger affinity N501Y-containing Docking four possible disaccharides mutant predicted potential binding poses constructs favorable close proximity 501Y residue. Our results demonstrate depolymerization fractionation effective segregate its property action. A global pandemic caused severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease-19 (Covid-19) declared World Health Organization March 2020 (1Peng M. Outbreak COVID-19: An emerging threat.Biomed. Pharmacother. 2020; 129: 110499Crossref PubMed Scopus (20) Google Scholar). virus has rapidly spread than 222 countries since February 2020. zoonotic beta transmitted person-to-person through droplets (2Stadnytskyi V. Bax C.E. A. Anfinrud P. airborne lifetime small speech their importance transmission.Proc. Natl. Acad. Sci. U. S. 117: 11875-11877Crossref (512) Scholar, 3Echternach Gantner Peters G. Westphalen C. Benthaus T. Jakubaß B. Kuranova L. Döllinger Kniesburges Impulse dispersion aerosols during singing speaking: COVID-19 transmission pathway.Am. J. Respir. Crit. Care Med. 202: 1584-1587Crossref (19) During pandemic, pharmaceutical companies started manufacturing vaccines, some which have been approved US Food Drug Administration under Emergency Use Authorization. Vaccines prevented patients becoming critically ill dying assisted controlling pandemic. Oral treatments Covid-19, molnupiravir paxlovid, recently issued Authorization currently awaiting full approval FDA (4Singh A.K. Singh R. Misra Molnupiravir systematic review literaturef.Diabetes Metab. Syndr. 2021; 15: 102329Crossref (28) 5Vandyck K. Deval Considerations discovery development 3-chymotrypsin-like cysteine protease inhibitors targeting infection.Curr. Opin. Virol. 49: 36-40Crossref (35) Nevertheless, new agents urgently needed, especially treating infections highly transmittable variants (6Moghaddar Radman Macreadie I. Severity, pathogenicity transmissibility delta lambda SARS-CoV-2, toxicity protein possibilities future prevention COVID-19.Microorganisms. 9: 2167Crossref (2) 7Ramesh Govindarajulu Parise R.S. Neel Shankar Patel Lowery Smith F. Dhanasekaran Moore Emerging variants: mutations, implications vaccine efficacy.Vaccines (Basel). 1195Crossref cell entry mechanism well studied. receptor-binding domain (RBD) S1 subunit spike-protein (S-protein) recognizes heparan sulfate (HS) surface proteoglycans human angiotensin-converting enzyme 2 (hACE2) (8Shang Wan Y. Luo Ye Geng Q. Auerbach Li Cell mechanisms SARS-CoV-2.Proc. 11727-11734Crossref (1318) 9Li Receptor recognition coronaviruses: decade structural studies.J. 2015; 89: 1954-1964Crossref (328) 10Kuhn J.H. W. Choe H. Farzan Angiotensin-converting 2: functional receptor SARS coronavirus.Cell. Mol. Life 2004; 61: 2738-2743Crossref (150) 11Li Harrison S.C. Structure complexed receptor.Science. 2005; 309: 1864-1868Crossref (1224) 12Clausen T.M. Sandoval D.R. Spliid C.B. Pihl Perrett H.R. Painter C.D. Narayanan Majowicz S.A. Kwong E.M. McVicar R.N. Thacker B.E. Glass C.A. Yang Z. Torres J.L. Golden G.J. et al.SARS-CoV-2 infection depends on cellular ACE2.Cell. 183: 1043-1057.e15Abstract Full Text PDF (376) Structural analyses revealed behind between SARS-CoV RBD host hACE2 (13Wan Shang Graham Baric novel Wuhan: analysis based decade-long studies coronavirus.J. 94e00127-20Crossref (2436) 14Lan Ge Yu Shan Zhou Fan Zhang Shi X. Wang bound ACE2 receptor.Nature. 581: 215-220Crossref (2418) heparin-binding site identified interaction HS shown essential (12Clausen Since binding, several recent proposed anti-SARV-CoV-2 effects exogenous such unfractionated (UFH), nonanticoagulant heparin, HS-based molecules lung other tissues order block (15Tandon Sharp J.S. Pomin V.H. Ashpole N.M. Mitra D. McCandless M.G. Jin Liu Sharma Linhardt R.J. Effective inhibition enoxaparin derivatives.J. 95e01987-20Crossref (65) 16Mycroft-West C.J. Su Pagani Rudd T.R. Elli Guimond S.E. Miller Meneghetti M.C.Z. Nader H.B. Nunes Q.M. Procter Mancini N. Clementi Bisio al.Heparin inhibits invasion SARS-CoV-2: dependence (spike) heparin.bioRxiv. ([preprint])https://doi.org/10.1101/2020.04.28.066761Crossref (0) 17Li Pang S.J. Heparin interacts main activity.Spectrochim. Acta Biomol. Spectrosc. 2022; 267: 120595Crossref However, may present side complications hemorrhage (18Warkentin T.E. Levine M.N. Hirsh Horsewood Roberts Gent Kelton J.G. Heparin-induced thrombocytopenia treated low-molecular-weight heparin.N. Engl. 1995; 332: 1330-1335Crossref (2148) 19Hirsh Anand S.S. Halperin Fuster American Heart AssociationGuide therapy: Heparin: statement healthcare professionals Association.Circulation. 2001; 103: 2994-3018Crossref (385) Scholar), (20King D.J. Heparin-associated thrombocytopenia.Ann. Intern. 1984; 100: 535-540Crossref (390) 21Warkentin thrombocytopenia.Annu. Rev. 1989; 40: 31-44Crossref (112) osteoporosis (22Ginsberg anticoagulants pregnancy.Chest. 95: 156S-160SAbstract 23Ginsberg Kowalchuk Brill-Edwards Burrows Coates Webber effect bone density.Thromb. Haemost. 1990; 64: 286-289Crossref (113) hypersensitivity reactions (24Curry Bardana E.J. Pirofsky sensitivity. Report case.Arch. 1973; 132: 744-745Crossref hypoaldosteronism (25O'Kelly Magee McKenna T.J. Routine therapy adrenal aldosterone production.J. Clin. Endocrinol. 1983; 56: 108-112Crossref (70) Hence, reports showing nonheparin glycans, unique marine sources, appeared literature (26Salih A.E.M. Thissera Yaseen Hassane A.S.I. El-Seedi Sayed A.M. Rateb M.E. Marine polysaccharides promising agents: comprehensive report modeling study focusing CoV-2.Mar. Drugs. 19: 406Crossref (7) 27Chen Han Zhao Application prospect anti-novel drugs vaccines.Int. Biol. Macromol. 164: 331-343Crossref (62) 28Jin Tandon structure-activity relationship glycoproteins glucuronomannan galactofucan Saccharina japonica.Int. 163: 1649-1658Crossref (25) 29Ray Schütz Mukherjee Jana Ray Marschall Exploiting amazing diversity natural source-derived polysaccharides: Modern procedures isolation, engineering, optimization activities.Polymers 13: 136Crossref (9) 30Aranda Wicklein Ruiz-Garcia Martín-Sampedro Darder Del Real Ruiz-Hitzky E. Research patents review.Recent Pat. Nanotechnol. 14: 328-350Crossref (4) studied only Wuhan strain (WT) mutated variants, those infectious potency. Viral mutation naturally generated multiple viral replications (31Grubaugh N.D. Petrone Holmes E.C. shouldn't worry when mutates disease outbreaks.Nat. Microbiol. 5: 529-530Crossref (79) RNA viruses frequently randomly at higher frequency DNA because polymerases lack exonuclease proofreading (32Ferron Subissi Silveira De Morais A.T. Le N.T.T. Sevajol Gluais Decroly Vonrhein Bricogne Canard Imbert basis mismatch correction ribavirin excision RNA.Proc. 2018; 115: E162-E171Crossref (187) Among all viruses, coronaviruses mutate less due corrects errors Nonetheless, number increasing, mainly Variants worldwide, few considered concern (VOC) harmful impact health. Such VOC greater transmissibility, virulence, immune escape mutations (33Shahhosseini Babuadze G.G. Wong Kobinger G.P. Mutation signatures silico docking concern.Microorganisms. 926Crossref (12) emerged among Alpha improves receptors enhances virulence (https://www.gavi.org/vaccineswork/alpha-omicron-everything-you-need-know-about-coronavirus-variants-concern). Current include (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron (B.1.1.529) located VOCs except Delta. This associated highest given rise lineages additional (34Huang Zhu Niu Sun mouse.Cell Death Differ. 28: 2840-2842Crossref emergence triple-mutated variant (K417T, E484K, N501Y, B.1.1.28), referred reported Brazil (35Fujino Nomoto Kutsuna Ujiie Suzuki Sato Fujimoto Kuroda Wakita Ohmagari Novel travelers Japan.Emerg. Infect. Dis. 27: 1243-1245Crossref (75) 36de Siqueira I.C. Camelier A.A. Maciel E.A.P. Nonaka C.K.V. Neves M.C.L.C. Macêdo Y.S.F. de Sousa K.A.F. Araujo V.C. Paste Souza B.S.d.F. Gräf Early detection P.1 cluster cases Salvador, Brazil.Int. 108: 252-255Abstract 37Romano C.M. Felix A.C. Paula A.V. Jesus Andrade P.S. Cândido Oliveira F.M. Ribeiro da Silva F.C. Inemami Costa Leal C.O.D. Figueiredo W.M. Pannuti C.S. reinfection lineage Araraquara City, Sao Paulo State, Brazil.Rev. Inst. Trop. Paulo. 63: e36Crossref 38Prajapat Handa Sarma Prakash Kaur Bhattacharyya Kumar A.R. Avti Medhi Update geographical variation distribution SARS-nCoV-2: review.Indian Pharmacol. 53: 310-316PubMed high transmissible rates, inherent neutralizing antibodies (39Greaney A.J. Loes A.N. Crawford K.H.D. Starr T.N. Malone K.D. Chu H.Y. Bloom J.D. Comprehensive mapping affect polyclonal serum antibodies.bioRxiv. ([preprint])https://doi.org/10.1101/2020.12.31.425021Crossref 40Baum Fulton B.O. Wloga Copin Pascal K.E. Russo Giordano Lanza Negron Ni Wei Atwal G.S. Murphy Stahl Yancopoulos G.D. al.Antibody cocktail prevents rapid mutational individual antibodies.Science. 369: 1014-1018Crossref (577) 41Liu VanBlargan L.A. Rothlauf P.W. Bloyet L.-M. Chen R.E. Stumpf Errico J.M. Theel E.S. Ellebedy Fremont Diamond M.S. Whelan S.P.J. Landscape identifies attenuate monoclonal antibody neutralization.SSRN Electron. https://doi.org/10.2139/ssrn.3725763Crossref increased propensity reinfection. glycan isolated occidentalis, (BoSG), well-characterized possess (42Pomin Mahdi Paris J.J. Red algal binds protects neural HIV-1 gp120 Tat.Pharmaceuticals 714Crossref (1) 43Zoepfl Dwivedi Taylor M.C. McVoy M.A. Antiviral adenovirus cytomegalovirus.Antiviral Res. 190: 105077Crossref Scholar) antimalarial (44Marques Vilanova Mourão P.A.S. Fernàndez-Busquets organism exhibiting significant Plasmodium.Sci. Rep. 2016; 6: 24368Crossref (36) (45Glauser B.F. serpin-unrelated properties.Adv. Chem. 2013; 62: 269-303Crossref (11) 46Melo F.R. unusual dual venous thrombosis activation factor XII proteases.Thromb. 2008; 99: 531-538Crossref (39) 47Pereira Benevides N.M.B. Melo M.R.S. Valente A.P. alga, Gelidium crinale. Is there specific requirement action?.Carbohydr. 340: 2015-2023Crossref (141) 48Farias W.R.L. A.-P. Pereira galactans.J. 2000; 275: 29299-29307Abstract (230) antithrombotic (46Melo 49Melo Foguel Antithrombin-mediated polysaccharides.J. 279: 20824-20835Abstract (138) 50Quinderé A.-L.G. Santos G.R.C. S.-N.M.C.G. Glauser Fontes B.P. Queiroz I.N.L. galactans independent serpin?.J. Thromb. 2014; 12: 43-53Crossref activities. homogeneous terms backbone, disaccharide repeating unit [→4)-α-D-Gal-(1→3)-β-D-Gal-(1→], very heterogenous sulfation (Fig. 1A). properties widely strong responses systems (51Dwivedi antithrombotics.Mar. 18: 514Crossref 52Carvalhal Cristelo R.R. Resende D.I.S.P. Pinto M.M.M. Correia-da-Silva Antithrombotics sea: Polysaccharides beyond.Mar. 2019; 17: 170Crossref 53Mourão Perspective use organisms source drugs.Mar. 2770-2784Crossref (66) Studies regarding action indicated toward cofactor II (HCII) antithrombin (AT), dependency (47Pereira Here, analyze structural, anti-SARS-CoV-2, anticoagulant, S-protein-binding derivatives. For this, multifaceted approach used analytical biophysical techniques, liquid-chromatography, electrophoresis, NMR, mass spectrometry (MS), (SPR), computational docking, measuring SARS-CoV-2. generate oligosaccharides residual while retaining activity. Crude obtained body wall nonspecific proteolytic digestion papain followed ethanol precipitation, previously described (48Farias 54Zucker Buttle Nicklin M.J.H. Barrett chymopapain, papain, papaya proteinase III.Biochim. Biophys. Acta. 1985; 828: 196-204Crossref (96) 55Tsou C.L. Cytochrome c modified enzymes. 1. Digestion.Biochem. 1951; 362-367Crossref (68) crude subjected anion-exchange chromatography DEAE Sephacel column eluted linear NaCl gradient up 3 M concentration S1A). metachromasia 1,9-dimethylmethylene blue (DMB) (56Farndale R.W. Sayers direct spectrophotometric microassay glycosaminoglycans cartilage cultures.Connect. Tissue 1982; 247-248Crossref (1137) peak corresponding elute 0.9 After pooling belonging desalination, integrity preparation 1D 1H NMR S1B), demonstrating spectral similar previous work Mild acid hydrolysis routinely digestive enzymes unknown (57Pomin Tollefsen D.M. Pavão M.S.G. Selective cleavage fucan: Stereospecific removal 2-sulfate ester polysaccharide mild hydrolysis, oligosaccharides, II-dependent activity.Glycobiology. 369-381Crossref (95) 58Pomin fucans: 2-desulfation reaction alternative preparing tailored oligosaccharides.Glycobiology. 1376-1385Crossref (69) 59Queiroz Vilela-Silva A.-C.E.S. Oligosaccharides 3-linked 2-sulfated alpha-L-fucan alpha-L-galactan show conformations dynamics.Glycobiology. 26: 1257-1264PubMed choice 0.1 hydrochloric 60 °C temperature produce above could suitable further size-exclusion (SEC), times (1, 3, 5, 7, 9, 11 h) evaluated. distributions analyzed PAGE S2). Large-scale production then made 7 h time yielded range medium-sized filtered Bio-Gel P-10 column. Approximately, 30 mg employed oligosaccharides. SEC 60Pomin Park Huang Heiss Azadi Prestegard specificities digestions chondroitin sulfates C: Production well-defined hexasaccharides.Glycobiology. 2012; 22: 826-838Crossref (30) 61Queiroz Glushka J.N. Woods Impact conformation dynamics fucan MD.Glycobiology. 25: 535-547Crossref (16) medium- and/or small-sized Figure 1B shows chromatographic profile metachromasy. Although no resolved peaks indicative size-defined evident, (Fr1–Fr4) pooled. As 1C), oligosaccharide

Language: Английский

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mRNA-LNP COVID-19 vaccine lipids induce low level complement activation and production of proinflammatory cytokines: Mechanisms, effects of complement inhibitors, and relevance to adverse reactions

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 15, 2024

ABSTRACT Messenger RNA-containing lipid nanoparticles (mRNA-LNPs) enabled widespread COVID-19 vaccination with a small fraction of vaccine recipients displaying acute or sub-acute inflammatory symptoms. The molecular mechanism these adverse events (AEs) remains undetermined. Here we report that the mRNA-LNP vaccine, Comirnaty, triggers low-level complement (C) activation and production cytokines, which may be key underlying processes AEs. In serum, Comirnaty control PEGylated liposome (Doxebo) caused different rises C split products, C5a, sC5b-9, Bb C4d, indicating stimulation classical pathway mainly by liposomes, while stronger alternative was equal liposomes. Spikevax had similar as but viral synthetic mRNAs no such effect. autologous serum-supplemented peripheral blood mononuclear cell (PBMC) cultures, increases in levels sC5b-9 proinflammatory cytokines following order: IL-1α < IFN-γ IL-1β TNF-α IL-6 IL-8, whereas heatinactivation serum prevented IL-1α, IL-1β, TNF-α. Clinical inhibitors, Soliris Berinert, suppressed vaccine-induced did not affect cytokine when applied individually. These findings suggest coating can trigger via pathway, causally related to induction some, all cytokines. While innate immune is essential for vaccine’s efficacy, concurrent C- PBMC-derived mediators contribute some Pharmacological attenuation harmful using inhibitors likely requires blocking cascade at multiple points.

Language: Английский

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