Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1 and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster

Nature Medicine, Год журнала: 2022, Номер 29(2), С. 344 - 347

Опубликована: Дек. 6, 2022

Язык: Английский

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Substantial Neutralization Escape by SARS-CoV-2 Omicron Variants BQ.1.1 and XBB.1

New England Journal of Medicine, Год журнала: 2023, Номер 388(7), С. 662 - 664

Опубликована: Янв. 18, 2023

ed another putative factor directly stimulating testicular testosterone secretion.LH and hCG are structurally similar, promotes secretion through stimulation of the LH receptors on Leydig cells (Fig. S1 in Supplementary Appendix, available with full text this letter at NEJM.org), thus maintaining normal even absence stimulation.Normal adrenal glands imaging low levels during degarelix treatment ruled out an or pituitary source our patient.Germ-cell tumors most common ectopic production; thus, performing ultrasonography to locate a germ-cell tumor should be first step patients nonsuppressible androgen-deprivation therapy.Lung, gastrointestinal, urothelial cancers also considered, because they can produce hCG.High-grade carcinomas dedifferentiate into syncytiotrophoblasts that hCG. 4,5These may present hematuria, macroorchidism, gynecomastia, surgical pathological examination would confirm presence positive staining.When clinicians encounter whose do not decrease androgendeprivation therapy who have levels, consideration exogenous use testosterone, androgens, hormone is warranted.We recommend measuring such patients.

Язык: Английский

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COVID-19, post-acute COVID-19 syndrome (PACS, “long COVID”) and post-COVID-19 vaccination syndrome (PCVS, “post-COVIDvac-syndrome”): Similarities and differences

Pathology - Research and Practice, Год журнала: 2023, Номер 246, С. 154497 - 154497

Опубликована: Май 3, 2023

Worldwide there have been over 760 million confirmed coronavirus disease 2019 (COVID-19) cases, and 13 billion COVID-19 vaccine doses administered as of April 2023, according to the World Health Organization. An infection with severe acute respiratory syndrome 2 (SARS-CoV-2) can lead an disease, i.e. COVID-19, but also a post-acute (PACS, "long COVID"). Currently, side effects vaccines are increasingly being noted studied. Here, we summarise currently available indications discuss our conclusions that (i) these specific similarities differences PACS, (ii) new term should be used refer (post-COVID-19 vaccination syndrome, PCVS, colloquially "post-COVIDvac-syndrome"), (iii) is need distinguish between (ACVS) (PACVS) - in analogy PACS ("long Moreover, address mixed forms caused by natural SARS-CoV-2 vaccination. We explain why it important for medical diagnosis, care research use terms (PCVS, ACVS PACVS) order avoid confusion misinterpretation underlying causes enable optimal therapy. do not recommend "Post-Vac-Syndrome" imprecise. The article serves current problem "medical gaslighting" relation PCVS raising awareness among professionals supplying appropriate terminology disease.

Язык: Английский

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Drug delivery systems for CRISPR-based genome editors

Nature Reviews Drug Discovery, Год журнала: 2023, Номер 22(11), С. 875 - 894

Опубликована: Сен. 18, 2023

Язык: Английский

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Insights for COVID-19 in 2023

Revista Española de Quimioterapia, Год журнала: 2022, Номер 36(2), С. 114 - 124

Опубликована: Дек. 12, 2022

Predictions for a near end of the pandemic by World Health Organization should be interpreted with caution. Current evidence indicates that efficacy fourth dose classical mRNA vaccines (BT162b2 or mRNA-1273) is low and short-lived in preventing SARS-CoV-2 infection its predominant variant (Omicron). However, high against severe symptomatic infection, hospitalization death. The new being introduced are bivalent active Omicron variants. Potential to coming year include vaccine based on recombinant protein emulates receptor binding domain Spike under development Spanish company Hipra, as well nasal oral administration. Available information suggests COVID-19 can administered association influenza vaccination without particular complications. New drugs COVID-19, both antiviral anti-inflammatory, investigation, but this does not seem case monoclonal antibodies. indication use masks some circumstances will maintained next view accumulation scientific data their efficacy. Finally, long COVID Post-COVID syndrome may continue affect very proportion patients who have had disease, requiring combined diagnostic therapeutic resources.

Язык: Английский

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Principles and therapeutic applications of adaptive immunity

Cell, Год журнала: 2024, Номер 187(9), С. 2052 - 2078

Опубликована: Апрель 1, 2024

Adaptive immunity provides protection against infectious and malignant diseases. These effects are mediated by lymphocytes that sense respond with targeted precision to perturbations induced pathogens tissue damage. Here, we review key principles underlying adaptive orchestrated distinct T cell B populations their extensions disease therapies. We discuss the intracellular intercellular processes shaping antigen specificity recognition in immune activation lymphocyte functions mediating effector memory responses. also describe how balance protective autoimmunity immunopathology, including during tolerance, response chronic stimulation, adaptation non-lymphoid tissues coordinating homeostasis. Finally, extracellular signals cell-intrinsic programs underpinning conclude summarizing advances vaccination engineering responses for therapeutic interventions. A deeper understanding of these holds promise uncovering new means improve human health.

Язык: Английский

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Strategies to reduce the risks of mRNA drug and vaccine toxicity

Nature Reviews Drug Discovery, Год журнала: 2024, Номер 23(4), С. 281 - 300

Опубликована: Янв. 23, 2024

Язык: Английский

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Determinants of COVID-19 vaccine fatigue

Nature Medicine, Год журнала: 2023, Номер 29(5), С. 1164 - 1171

Опубликована: Март 27, 2023

There is growing concern that Coronavirus Disease 2019 (COVID-19) vaccine fatigue will be a major obstacle in maintaining immunity the general population. In this study, we assessed acceptance future scenarios two conjoint experiments, investigating determinants such as new vaccines, communication, costs/incentives and legal rules. The experiments were embedded an online survey (n = 6,357 participants) conducted European countries (Austria Italy). Our results suggest vaccination campaigns should tailored to subgroups based on their status. Among unvaccinated, campaign messages conveying community spirit had positive effect (0.343, confidence interval (CI) 0.019-0.666), whereas offering incentives, cash reward (0.722, CI 0.429-1.014) or voucher (0.670, 0.373-0.967), was pivotal decision-making of those vaccinated once twice. triple vaccinated, readiness increased when adapted vaccines offered (0.279, 0.182-0.377), but costs (-0.795, -0.935 -0.654) medical dissensus (-0.161, -0.293 -0.030) reduced likelihood get vaccinated. We conclude failing mobilize likely result booster rates falling short expectations. For long-term success, measures fostering institutional trust considered. These provide guidance responsible for COVID-19 campaigns.

Язык: Английский

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Spleen SORT LNP Generated in situ CAR T Cells Extend Survival in a Mouse Model of Lymphoreplete B Cell Lymphoma

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(44)

Опубликована: Авг. 31, 2023

Abstract Chimeric Antigen Receptor (CAR) T cell immunotherapy is revolutionizing treatment for patients suffering from B‐cell lymphoma (BL). However, the current method of CAR production complicated and expensive, requiring collection patient blood to enrich population, ex vivo engineering/activation, quality assessment before can receive treatment. Herein we leverage Spleen Selective ORgan Targeted (SORT) Lipid Nanoparticles (LNPs) produce cells in situ bypass extensive laborious process currently used. Optimized SORT LNPs containing 10 % 18 : 1 PA transfected CD3+, CD8+, CD4+ wild‐type mice. delivered Cre recombinase mRNA encoding reporter mice a lymphoreplete B model (respectively) after intravenous injection without need active targeting ligands. Moreover, increased overall survival with less aggressive form lymphoma. In addition, reduced tumor metastasis liver by increasing infiltrating lymphocytes. Overall, these results offer promising alternative pre‐clinical potential treat hematological malignancies.

Язык: Английский

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ESCRT recruitment to SARS-CoV-2 spike induces virus-like particles that improve mRNA vaccines

Cell, Год журнала: 2023, Номер 186(11), С. 2380 - 2391.e9

Опубликована: Апрель 21, 2023

Prime-boost regimens for COVID-19 vaccines elicit poor antibody responses against Omicron-based variants and employ frequent boosters to maintain levels. We present a natural infection-mimicking technology that combines features of mRNA- protein nanoparticle-based through encoding self-assembling enveloped virus-like particles (eVLPs). eVLP assembly is achieved by inserting an ESCRT- ALIX-binding region (EABR) into the SARS-CoV-2 spike cytoplasmic tail, which recruits ESCRT proteins induce budding from cells. Purified spike-EABR eVLPs presented densely arrayed spikes elicited potent in mice. Two immunizations with mRNA-LNP CD8+ T cell superior neutralizing original variant compared conventional spike-encoding purified eVLPs, improving titers >10-fold 3 months post-boost. Thus, EABR enhances potency breadth vaccine-induced antigen presentation on surfaces enabling longer-lasting protection other viruses.

Язык: Английский

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