mRNA vaccine boosters and impaired immune system response in immune compromised individuals: a narrative review

Clinical and Experimental Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: Jan. 27, 2024

Abstract Over the last 24 months, there has been growing evidence of a correlation between mRNA COVID-19 vaccine boosters and increased prevalence infection other pathologies. Recent works have added possible causation to correlation. may impair immune system response in compromised individuals. Multiple doses vaccines result much higher levels IgG 4 antibodies, or also impaired activation CD4 + CD8 T cells. The opportunity for needs careful consideration, as this impacts cost-to-benefit ratio boosters’ practice.

Language: Английский

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Molecular Mimicry and HLA Polymorphisms May Drive Autoimmunity in Recipients of the BNT-162b2 mRNA Vaccine: A Computational Analysis

Microorganisms, Journal Year: 2023, Volume and Issue: 11(7), P. 1686 - 1686

Published: June 28, 2023

After the start of worldwide COVID-19 vaccination campaign, there were increased reports autoimmune diseases occurring de novo after vaccination. This in silico analysis aimed to investigate presence protein epitopes encoded by BNT-162b2 mRNA vaccine, one most widely administered vaccines, which could induce autoimmunity predisposed individuals.The FASTA sequence vaccine served as key input Immune Epitope Database and Analysis Resource. Linear peptides with 90% BLAST homology selected, T-cell, B-cell, MHC-ligand assays without MHC restriction searched analyzed. HLA disease associations screened on HLA-SPREAD platform selecting only positive markers.By 7 May 2023, a total 5693 corresponding 21 viral but also human proteins found. The latter included CHL1, ENTPD1, MEAF6, SLC35G2, ZFHX2. Importantly, some autoepitopes may be presented alleles positively associated various immunological diseases.The product contains immunogenic that trigger phenomena individuals through molecular mimicry mechanism. Genotyping for help identify at risk. However, further wet-lab studies are needed confirm this hypothesis.

Language: Английский

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mRNA Vaccines Against COVID-19 as Trailblazers for Other Human Infectious Diseases

Vaccines, Journal Year: 2024, Volume and Issue: 12(12), P. 1418 - 1418

Published: Dec. 16, 2024

mRNA vaccines represent a milestone in the history of vaccinology, because they are safe, very effective, quick and cost-effective to produce, easy adapt should antigen vary, able induce humoral cellular immunity. Methods: To date, only two COVID-19 one RSV have been approved. However, several currently under development for prevention human viral (influenza, immunodeficiency virus [HIV], Epstein–Barr virus, cytomegalovirus, Zika, respiratory syncytial metapneumovirus/parainfluenza 3, Chikungunya, Nipah, rabies, varicella zoster herpes simplex 1 2), bacterial (tuberculosis), parasitic (malaria) diseases. Results: RNA viruses, such as severe acute syndrome coronavirus (SARS-CoV)-2, HIV, influenza, characterized by high variability, thus creating need rapidly circulating strain, task that can easily accomplish; however, speed variability may be higher than time needed vaccine adapted. vaccines, using lipid nanoparticles delivery system, act adjuvants, powerfully stimulating innate well adaptive immunity, both humoral, which is waning, cell-mediated, highly persistent. Safety profiles were satisfactory, considering slight increase prognostically favorable anaphylactic reactions young females myopericarditis males has observed. Conclusions: The pandemic determined shift use RNA: after having used medicine micro-RNAs tumor new era anti-infectious begun, great development, either improve already available, but unsatisfactory, or develop protective against infectious agents no preventative tools realized yet.

Language: Английский

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Inhibitory effects of SARS-CoV-2 spike protein and BNT162b2 vaccine on erythropoietin-induced globin gene expression in erythroid precursor cells from patients with β-thalassemia

Experimental Hematology, Journal Year: 2023, Volume and Issue: 129, P. 104128 - 104128

Published: Nov. 6, 2023

During the recent COVID-19 pandemic several β-thalassemia patients have been infected by SARS-CoV-2 and most were vaccinated against SARS-CoV-2. Recent studies demonstrate an impact of infection on hematopoietic system. The main objective this study was to verify effects exposure erythroid precursor cells (ErPCs) from Spike protein (S-protein) BNT162b2 vaccine. Erythropoietin (EPO)-cultured ErPCs either untreated or treated with S-protein employed a cellular Biobank developed before pandemic. genotypes β+-IVSI-110/β+-IVSI-110 (one patient), β039/β+-IVSI-110 (three patients) β039/ β039 (two patients). After 5 days treatment BNT162b2, lysates analysed HPLC, for hemoglobin production, isolated RNA assayed RT-qPCR, detection globin gene expression. conclusions results obtained are that vaccine inhibit (a) fetal production β-thalassemic (b) γ-globin mRNA accumulation. In addition, we performed in silico suggesting high affinity (HbF). Remarkably, binding interaction energy comparable angiotensin-converting enzyme 2 (ACE2). Our consistent hypothesis relevant vaccination

Language: Английский

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The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells

Experimental Cell Research, Journal Year: 2023, Volume and Issue: 433(2), P. 113853 - 113853

Published: Nov. 7, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causative of the ongoing disease 2019 (COVID-19) pandemic. SARS-CoV-2 Spike protein (S-protein) plays an important role in early phase infection through efficient interaction with ACE2. S-protein produced by RNA-based COVID-19 vaccines, that were fundamental for reduction viral spread within population and clinical severity COVID-19. However, has been hypothesized to be responsible damaging cells several tissues some side effects vaccines. Considering impact on hematopoietic system, aim this study was verify effect BNT162b2 vaccine erythroid differentiation human K562 cell line, past intensively studied as a model system mimicking steps erythropoiesis. In context, we focused hemoglobin production induced expression embryo-fetal globin genes, are among most features differentiation. We found suppresses mithramycin-induced cells. Reverse-transcription-qPCR Western blotting assays demonstrated suppression associated sharp inhibition α-globin γ-globin mRNA accumulation. Inhibition accumulation ζ-globin ε-globin mRNAs also observed. addition, provide silico studies suggesting direct between Hb Portland, major This thus provides information need great attention possible alteration parameters following and/or vaccination.

Language: Английский

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The WHO Algorithm for Causality Assessment of Adverse Effects Following Immunization with Genetic-Based Anti-COVID-19 Vaccines: Pitfalls and Suggestions for Improvement

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(23), P. 7291 - 7291

Published: Nov. 30, 2024

Clarifying and differentiating the causes of diseases is an essential step in any clinical activity, but it takes on particular relevance complexity case that arise following vaccinations. The WHO has proposed a protocol uses list specific questions about vaccine-related adverse events algorithm for making judgement. Here, we analyze discuss important limitations this when applied to new genetic-based anti-COVID-19 vaccines, particularly once dealing with rare unexpected pathological events. main controversial aspects concern: (a) prevailing consideration other possible causes; (b) biological plausibility choice appropriate time window consider effects possibly caused by vaccines; (c) reference scientific literature, which may be very limited often early stages introducing vaccines because short period observation; (d) final classification into only three classes, leaves ample space "indeterminate" category. Failure address these issues lead distorted pharmacovigilance reports significant consequences benefit/harm assessment. In anticipation future pandemics managed needs revised protocols monitoring evaluation take account novel mechanism action real-world epidemiological data.

Language: Английский

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A protocol to differentiate the COVID-19 infection and vaccine experiences of patients with systemic, single site and overlap immune-mediated inflammatory disease (IMID) (Preprint)

Published: Nov. 13, 2024

Patients with immune-mediated inflammatory disease (IMID), including autoimmunity, fared significantly worse than the general population during COVID-19 pandemic both in terms of infection outcomes and levels life disruption. Despite this, vaccine uptake has not been universal. The absence IMID patients from clinical trials subsequent lack precision safety profiling adds to hesitancy this high-risk group. present protocol sets out an investigation that aims address by enhancing pharmacovigilance for IMID. Combining international data knowledge assets Vaccination Autoimmune Diseases (COVAD) 1 Study electronic Delphi Define Risk-Stratify Immunosuppression (DESTINIES), its objective is differentiate patient-reported between systemic, single site overlap controls. COVAD successfully collected on demographic, health, vaccination a broad range March December 2021. expands initial analysis, utilising expertise within DESTINIES Consortium allocate survey respondents into systemic categories thereby produce comparative benefit-risk profiles these Due respondents’ ability self-declare multiple diagnoses, group was introduced those affected diagnoses. Descriptive statistics, Chi-squared tests independence, incidence rate ratios multivariable logistic regressions will be utilised test significant differences COVID rates, severity, duration side effects populations. We anticipate more severe (hospitalisation without Oxygen support) (mild major) were reported amongst patients. expect moderated factors age, prior health status medication, however. multimorbidity category also expected result increased adverse compared exclusively Advocating direct-to-patient reporting pathways, study intends provide precise It seeks current gaps potentially remedy groups doing so.

Language: Английский

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Effect of the COVID‐19 pandemic on disease activity in multiple sclerosis patients treated with hematopoietic stem cell transplantation

European Journal of Neurology, Journal Year: 2023, Volume and Issue: 30(10), P. 3362 - 3366

Published: July 22, 2023

It is still debated whether the COVID-19 pandemic affected disease activity in people with autoimmune diseases, including multiple sclerosis (MS). The aim of this study, therefore, was to explore impact MS (pwMS) not receiving continuative disease-modifying therapy (DMT) after previous treatment autologous hematopoietic stem cell transplantation (AHSCT).We included pwMS treated AHSCT who were remission without DMTs during and followed up at our centre study period. Data on SARS-CoV-2 infection vaccination recorded, details adverse events clinical-radiological activity.A total 36 (31 females; 86%) included, whom 23 (64%) had relapsing-remitting (RR-MS) 13 secondary progressive (SP-MS). Thirty-three (92%) received anti-SARS-CoV-2 mRNA vaccines. Thirteen patients (36%) developed mild moderate a median (range) 58 (4-224) months AHSCT; seven (54%) these yet vaccinated. Transient neurological symptoms or reported 9% 36% patients, respectively. rate new inflammatory (relapses asymptomatic magnetic resonance imaging [MRI] activity) increased from 0.006 (one lesion/159 patient-years) before 0.083 (five relapses plus two cases MRI activity/84 since start (p = 0.004).People history highly active disease, are untreated moderate-efficacy might be more vulnerable reactivation, possibly elicited by exogenous triggers. Careful monitoring further investigation warranted ascertain special precautions needed cases.

Language: Английский

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The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 7, 2023

ABSTRACT The COVID-19 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the ongoing disease 2019 (COVID-19) pandemic. SARS-CoV-2 Spike protein (S-protein) plays an important role in early phase of SARS-CoV2 infection through efficient interaction with ACE2. S-protein is produced by RNA-based vaccines, and has been hypothesized to be responsible for damaging cells several tissues some side effects vaccines. aim this study was verify effect BNT162b2 vaccine on erythroid differentiation human K562 cell line, that past intensively studied as a model system mimicking steps erythropoiesis. We found suppresses mithramycin-induced cells. Reverse-transcription-PCR Western blotting assays demonstrated suppression associated sharp inhibition expression α-globin γ-globin mRNA accumulation. Inhibition accumulation ζ-globin ε-globin mRNAs also observed. In addition, we provide silico studies suggesting direct between Hb Portland, major hemoglobin This thus provides information need great attention possible alteration hematopoietic parameters following and/or vaccination.

Language: Английский

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The Antiviral Activity of the Lectin Griffithsin against SARS-CoV-2 Is Enhanced by the Presence of Structural Proteins

Viruses, Journal Year: 2023, Volume and Issue: 15(12), P. 2452 - 2452

Published: Dec. 18, 2023

Although COVID-19 transmission has been reduced by the advent of vaccinations and a variety rapid monitoring techniques, SARS-CoV-2 virus itself shown remarkable ability to mutate persist. With this long track record immune escape, researchers are still exploring prophylactic treatments curtail future variants. Specifically, much focus placed on antiviral lectin Griffithsin in preventing spike protein-mediated infection via hACE2 receptor (direct infection). However, an oft-overlooked aspect is viral capture attachment receptors such as DC-SIGN, which thought facilitate initial stages lung tissue (called trans-infection). In addition, while escape dictated mutations protein, coronaviral virions also incorporate M, N, E structural proteins within particle. paper, we explored how several facets both virion can affect attenuate infectivity pseudovirus. We found that was better inhibitor hACE2-mediated direct when M protein present compared it absent (possibly providing explanation regarding why shows inhibition against authentic opposed pseudotyped viruses, generally do not contain M) effective DC-SIGN-mediated trans-infection. Furthermore, DC-SIGN appeared mediate trans-infection exclusively binding with no significant effect observed other (M, and/or E) were present. These results provide etiological data may help development novel treatments, either leveraging strategy prevent or narrowing efforts inhibit protein.

Language: Английский

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