mRNA-based therapeutics: powerful and versatile tools to combat diseases

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: May 21, 2022

Abstract The therapeutic use of messenger RNA (mRNA) has fueled great hope to combat a wide range incurable diseases. Recent rapid advances in biotechnology and molecular medicine have enabled the production almost any functional protein/peptide human body by introducing mRNA as vaccine or agent. This represents rising precision field with promise for preventing treating many intractable genetic In addition, vitro transcribed achieved programmed production, which is more effective, faster design well flexible cost-effective than conventional approaches that may offer. Based on these extraordinary advantages, vaccines characteristics swiftest response large-scale outbreaks infectious diseases, such currently devastating pandemic COVID-19. It always been scientists’ desire improve stability, immunogenicity, translation efficiency, delivery system achieve efficient safe mRNA. Excitingly, scientific dreams gradually realized rapid, amazing achievements biology, technology, vaccinology, nanotechnology. this review, we comprehensively describe mRNA-based therapeutics, including their principles, manufacture, application, effects, shortcomings. We also highlight importance optimization systems successful therapeutics discuss key challenges opportunities developing tools into powerful versatile genetic, infectious, cancer, other refractory

Language: Английский

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Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis

BMJ, Journal Year: 2022, Volume and Issue: unknown, P. e068632 - e068632

Published: March 2, 2022

Abstract Objective To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people. Design Systematic review meta-analysis. Data sources PubMed, Embase, Central Register Controlled Trials, COVID-19 Open Research Dataset Challenge (CORD-19), WHO databases for studies published 1 December 2020 5 November 2021. ClinicalTrials.gov International Clinical Trials Registry Platform were searched in 2021 to identify registered but as yet unpublished or ongoing studies. Study selection Prospective observational comparing vaccination participants. Methods A frequentist random effects meta-analysis was used separately pool relative absolute risks seroconversion after first second doses a vaccine. without SARS-CoV-2 antibody titre levels performed first, second, third vaccine rate dose. Risk bias certainty evidence assessed. Results 82 included Of these studies, 77 (94%) mRNA vaccines, 16 (20%) viral vector 4 (5%) inactivated whole virus vaccines. 63 assessed be at low risk 19 moderate bias. After one dose, about half likely patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 0.50, I 2 =80%; 0.29, 0.20 =89%), immune mediated inflammatory disorders (0.53, 0.39 0.71, =89%; 0.11 0.58, =97%), solid (0.55, 0.46 0.65, =78%; 0.44, 0.36 0.53, =84%) compared controls, whereas organ transplant recipients times less seroconvert (0.06, 0.04 0.09, =0%; 0.06, 0.08, =0%). remained least (0.39, 0.46, =92%; 0.35, 0.26 0.46), only achieving seroconversion. Seroconversion increasingly (0.63, 0.57 0.69, =88%; 0.62, 0.54 0.70, =90%), (0.75, 0.69 0.82, 0.77, 0.66 0.85, =93%), (0.90, 0.88 0.93, =51%; 0.89, 0.86 0.91, =49%). similar people HIV controls (1.00, 0.98 1.01, 0.97, 0.83 1.00, =89%). 11 showed that dose associated among non-responders cancers, disorders, although response variable inadequately studied those receiving non-mRNA Conclusion rates significantly lower patients, especially recipients. consistently improved across all patient groups, albeit magnitude Targeted interventions including (booster) should performed. registration PROSPERO CRD42021272088.

Language: Английский

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Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(11), P. 2002 - 2011

Published: Sept. 30, 2021

Language: Английский

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Effectiveness of 2-Dose Vaccination with mRNA COVID-19 Vaccines Against COVID-19–Associated Hospitalizations Among Immunocompromised Adults — Nine States, January–September 2021

MMWR Morbidity and Mortality Weekly Report, Journal Year: 2021, Volume and Issue: 70(44), P. 1553 - 1559

Published: Nov. 2, 2021

Immunocompromised persons, defined as those with suppressed humoral or cellular immunity resulting from health conditions medications, account for approximately 3% of the U.S. adult population (1). adults are at increased risk severe COVID-19 outcomes (2) and might not acquire same level protection mRNA vaccines do immunocompetent (3,4). To evaluate vaccine effectiveness (VE) among immunocompromised adults, data VISION Network* on hospitalizations persons aged ≥18 years COVID-19-like illness 187 hospitals in nine states during January 17-September 5, 2021 were analyzed. Using selected discharge diagnoses,† VE against COVID-19-associated hospitalization conferred by completing a 2-dose series an ≥14 days before index date§ (i.e., being fully vaccinated) was evaluated using test-negative design comparing 20,101 (10,564 [53%] whom 69,116 (29,456 [43%] vaccinated). 2 doses lower patients (77%; 95% confidence interval [CI] = 74%-80%) than (90%; CI 89%-91%). This difference persisted irrespective product, age group, timing relative to SARS-CoV-2 (the virus that causes COVID-19) B.1.617.2 (Delta) variant predominance state hospitalization. varied across immunocompromising condition subgroups, ranging 59% (organ stem cell transplant recipients) 81% (persons rheumatologic inflammatory disorder). benefit vaccination but less protected varies subgroups. receiving should receive 3 booster, consistent CDC recommendations (5), practice nonpharmaceutical interventions, and, if infected, be monitored closely considered early proven therapies can prevent outcomes.

Language: Английский

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COVID-19 in people with rheumatic diseases: risks, outcomes, treatment considerations

Nature Reviews Rheumatology, Journal Year: 2022, Volume and Issue: 18(4), P. 191 - 204

Published: Feb. 25, 2022

Language: Английский

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COVID-19 therapeutics: Challenges and directions for the future

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(15)

Published: April 6, 2022

The emergence of SARS-CoV-2 triggering the COVID-19 pandemic ranks as arguably greatest medical emergency last century. has highlighted health disparities both within and between countries will leave a lasting impact on global society. Nonetheless, substantial investment in life sciences over recent decades facilitated rapid scientific response with innovations viral characterization, testing, sequencing. Perhaps most remarkably, this permitted development highly effective vaccines, which are being distributed globally at unprecedented speed. In contrast, drug treatments for established disease have delivered limited benefits so far. Innovative approaches design execution large-scale clinical trials repurposing existing drugs saved many lives; however, more remain risk. review we describe challenges unmet needs, discuss therapeutics, address future opportunities. Consideration is given to factors that hindered order support planning next challenge allow cost-effective new therapeutics equitable delivery.

Language: Английский

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Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform

The Lancet Rheumatology, Journal Year: 2022, Volume and Issue: 4(7), P. e490 - e506

Published: June 9, 2022

The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities vary factors such as ethnicity. We aimed to assess the adults those therapies.

Language: Английский

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SARS-CoV-2 in immunocompromised individuals

Immunity, Journal Year: 2022, Volume and Issue: 55(10), P. 1779 - 1798

Published: Sept. 13, 2022

Language: Английский

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American College of Rheumatology Guidance for COVID‐19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 5

Arthritis & Rheumatology, Journal Year: 2022, Volume and Issue: 75(1)

Published: Nov. 8, 2022

To provide guidance to rheumatology providers on the use of COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases (RMDs).A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious specialists, public health physicians. After agreeing scoping questions, an evidence report created summarized published literature publicly available data regarding vaccine efficacy safety, as well other in RMD patients. Task members rated their agreement draft consensus statements a 9-point numerical scoring system, using modified Delphi process RAND/University California Los Angeles Appropriateness Method, refinement iteration over sessions. Consensus determined based distribution ratings.Despite paucity direct evidence, were developed by agreed upon vaccines, including supplemental/booster dosing, offer recommendations timing immunomodulatory therapies around time vaccination.These are intended direction care how best facilitate implementation vaccination strategies

Language: Английский

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Humoral immune responses to COVID-19 vaccination in people living with HIV receiving suppressive antiretroviral therapy

npj Vaccines, Journal Year: 2022, Volume and Issue: 7(1)

Published: Feb. 28, 2022

Abstract Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely characterized. We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD), ACE2 displacement and viral neutralization activities one month following first second vaccine doses, again 3 months dose, 100 adult PLWH 152 controls. All were receiving suppressive antiretroviral therapy, median CD4+ T-cell counts of 710 (IQR 525–935) cells/mm , though nadir ranged as low <10 . After adjustment for sociodemographic, health vaccine-related variables, infection was associated lower anti-RBD antibody concentrations activity after dose. Following two doses however, not significantly magnitude any humoral response multivariable adjustment. Rather, older age, a higher burden chronic conditions, dual ChAdOx1 vaccination doses. No significant correlation observed between recent or PLWH. These results indicate that well-controlled loads healthy range generally mount strong initial vaccination. Factors including co-morbidities, brand, durability rise new variants will influence when benefit from additional Further studies who are treatment have needed, longer-term assessments durability.

Language: Английский

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