Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 471
Filter
1.
Theranostics ; 12(14): 6422-6436, 2022.
Article in English | MEDLINE | ID: covidwho-2203053

ABSTRACT

Rationale: Messenger RNA (mRNA) vaccine outperforms other kinds of cancer immunotherapy due to its high response rates, easy preparation, and wide applicability, which is considered as one of the most promising forms of next-generation cancer therapies. However, the inherent instability and insufficient protein expression duration of mRNA limit the efficacy and widespread application of the vaccine. Methods: Here, we first tested the possibility of a novel circular RNA (circRNA) platform for protein expression and compare its duration with linear RNA. Then, we developed a lipid nanoparticle (LNP) system for circRNA delivery in vitro and in vivo. Next, the innate and adaptive immune response of circRNA-LNP complex was evaluated in vivo. The anti-tumor efficacy of circRNA-LNP was further confirmed in three tumor models. Finally, the possibility of combination therapy with circRNA-LNP and adoptive cell transfer therapy was further investigated in a late-stage tumor model. Results: We successfully increased the stability of the RNA vaccine by circularizing the linear RNA molecules to form highly stable circRNA molecules which exhibited durable protein expression ability. By encapsulating the antigen-coding circRNA in LNP enabling in vivo expression, we established a novel circRNA vaccine platform, which was capable of triggering robust innate and adaptive immune activation and showed superior anti-tumor efficacy in multiple mouse tumor models. Conclusions: Overall, our circRNA vaccine platform provides a novel prospect for the development of cancer RNA vaccines in a wide range of hard-to-treat malignancies.


Subject(s)
Cancer Vaccines , Nanoparticles , Neoplasms , Animals , Liposomes , Mice , Neoplasms/therapy , RNA/genetics , RNA, Circular/genetics , RNA, Messenger/genetics , Vaccines, Synthetic , mRNA Vaccines
2.
PLoS One ; 17(6): e0270609, 2022.
Article in English | MEDLINE | ID: covidwho-2196920

ABSTRACT

Covid-19 progression shows sex-dependent features. It is hypothesized that a better Covid-19 survival rate in females can be attributed to the presence of higher 17ß-estradiol (E2) levels in women than in men. Virus SARS-CoV-2 is enabled to enter the cell with the use of angiotensin converting enzyme 2 (ACE2). The expression of several renin-angiotensin system components has been shown to exert a rhythmic pattern, and a role of the circadian system in their regulation has been implicated. Therefore, the aim of the study is to elucidate possible interference between E2 signalling and the circadian system in the regulation of the expression of ACE2 mRNA and functionally related molecules. E2 was administered at a dosage of 40 µg/kg/day for 7 days to male Wistar rats, and sampling of the lungs and colon was performed during a 24-h cycle. The daily pattern of expression of molecules facilitating SARS-CoV-2 entry into the cell, clock genes and E2 receptors was analysed. As a consequence of E2 administration, a rhythm in ACE2 and TMPRSS2 mRNA expression was observed in the lungs but not in the colon. ADAM17 mRNA expression showed a pronounced rhythmic pattern in both tissues that was not influenced by E2 treatment. ESR1 mRNA expression exerted a rhythmic pattern, which was diminished by E2 treatment. The influence of E2 administration on ESR2 and GPER1 mRNA expression was greater in the lungs than in the colon as a significant rhythm in ESR2 and GPER1 mRNA expression appeared only in the lungs after E2 treatment. E2 administration also increased the amplitude of bmal1 expression in the lungs, which implicates altered functioning of peripheral oscillators in response to E2 treatment. The daily pattern of components of the SARS-CoV-2 entrance pathway and their responsiveness to E2 should be considered in the timing of pharmacological therapy for Covid-19.


Subject(s)
ADAM17 Protein , Angiotensin-Converting Enzyme 2 , COVID-19 , Colon , Estradiol , Lung , Receptors, Estradiol , ADAM17 Protein/genetics , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19/drug therapy , COVID-19/virology , Colon/drug effects , Colon/metabolism , Estradiol/pharmacology , Female , Lung/metabolism , Male , Peptidyl-Dipeptidase A/metabolism , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Rats , Rats, Wistar , Receptors, Estradiol/genetics , Receptors, Estradiol/metabolism , SARS-CoV-2/physiology , Serine Endopeptidases/genetics , Transcription, Genetic/drug effects , Virus Internalization
4.
Front Cell Infect Microbiol ; 12: 960938, 2022.
Article in English | MEDLINE | ID: covidwho-2154694

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an extremely contagious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early disease recognition of COVID-19 is crucial not only for prompt diagnosis and treatment of the patients, but also for effective public health surveillance and response. The reverse transcription-polymerase chain reaction (RT-PCR) is the most common method for the detection of SARS-CoV-2 viral mRNA and is regarded as the gold standard test for COVID-19. However, this test and those for antibodies (IgM and IgG) and antigens have certain limitations (e.g., by yielding false-negative and false-positive results). We have developed an RNA fluorescence in situ hybridization (FISH) method for high-sensitivity detection of SARS-CoV-2 mRNAs in HEK 293T cell cultures as a model. After transfection of HEK 293T cells with plasmids, Spike (S)/envelope (E) proteins and their mRNAs were clearly detected inside the cells. In addition, hybridization time could be reduced to 2 hours for faster detection when probe concentration was increased. Our approach might thus significantly improve the sensitivity and specificity of SARS-CoV-2 detection and be widely applied for the high-sensitivity single-molecular detection of other RNA viruses (e.g., Middle East respiratory syndrome coronavirus (MERS-CoV), Hepatitis A virus, all influenza viruses, and human immunodeficiency virus (HIV)) in various types of samples including tissue, body fluid, blood, and water. RNA FISH can also be utilized for the detection of DNA viruses (e.g., Monkeypox virus, human papillomavirus (HPV), and cytomegalovirus (CMV)) by detection of their mRNAs inside cells or body fluid.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19 Testing , Clinical Laboratory Techniques/methods , RNA, Messenger/genetics , In Situ Hybridization, Fluorescence , HEK293 Cells , Immunoglobulin M , Immunoglobulin G , Water
5.
Invest New Drugs ; 40(6): 1173-1184, 2022 12.
Article in English | MEDLINE | ID: covidwho-2148841

ABSTRACT

Melanoma has a high degree of malignancy and mortality. While there are some hopeful clinical trials for melanoma treatment in progress, they have not yet to yield significant long-term cure rates. Cancer vaccines including mRNA are currently one of the most promising strategy for tumor immunotherapy. The aim of this study was to analyze the potential tumor antigens in melanoma that could be used to develop mRNA vaccines and identify suitable vaccine populations. The gene expression data and complete clinical information of 471 melanoma samples and 1 normal tissue were retrieved from TCGA. Then, 812 samples of normal skin and their corresponding gene expression data were obtained from GTEx. Overexpressed genes, mutated genes and IRDEGs are used to identify potential tumor antigens. The relationship between the expression level of potential antigen and prognosis was analyzed in GEPIA, and then the immune cell infiltration was estimated based on TIMER algorithm. The expression profiles of IRDEGs were used to identify consensus clusters and immune subtypes of melanoma. Finally, mutational status and immune microenvironment characterization in immune subtypes were analyzed. Five tumor antigens (PTPRC, SIGLEC10, CARD11, LILRB1, ADAMDEC1) were identified as potential tumor antigens according to overexpressed genes, mutated genes and immune-related genes. They were all associated with OS, DFS and APCs. We identified two immune subtypes of melanoma, named IS1 and IS2, which exhibit different clinical features and immune landscapes. Based on the different immune landscape, we may conclude that IS1 is immunophenotypically "cold", while IS2 is "hot". The present research implicates that PTPRC, SIGLEC10, CARD11, LILRB1 and ADAMDEC1 may be the antigenic targets for melanoma mRNA vaccines and IS2 patients may be more effective to these vaccines.


Subject(s)
Cancer Vaccines , Melanoma , Humans , Antigens, Neoplasm/genetics , Melanoma-Specific Antigens , Leukocyte Immunoglobulin-like Receptor B1 , Melanoma/genetics , Melanoma/therapy , Cancer Vaccines/therapeutic use , RNA, Messenger/genetics , Tumor Microenvironment
6.
Sci Adv ; 8(47): eabo1827, 2022 11 25.
Article in English | MEDLINE | ID: covidwho-2137352

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic underlines the urgent need for effective mRNA vaccines. However, current understanding of the immunological outcomes of mRNA vaccines formulated under different nanoplatforms is insufficient. Here, severe acute respiratory syndrome coronavirus 2 receptor binding domain mRNA delivered via lipid nanoparticle (LNP), cationic nanoemulsion (CNE), and cationic liposome (Lipo) was constructed. Results demonstrated that the structural and biochemical characteristics of nanoparticles shaped their tissue dissemination, cellular uptake, and intracellular trafficking, which eventually determined the activation of antiviral humoral and cellular immunity. Specifically, LNP was mainly internalized by myocyte and subsequently circumvented lysosome degradation, giving rise to humoral-biased immune responses. Meanwhile, CNE and Lipo induced cellular-preferred immunity, which was respectively attributed to the better lysosomal escape in dendritic cells and the superior biodistribution in secondary lymphoid organs. Overall, this study may guide the design and clinical use of mRNA vaccines against COVID-19.


Subject(s)
COVID-19 , Nanoparticles , Humans , SARS-CoV-2 , RNA, Messenger/genetics , COVID-19 Vaccines , Tissue Distribution , Immunity, Cellular
7.
Commun Biol ; 5(1): 1302, 2022 Nov 27.
Article in English | MEDLINE | ID: covidwho-2133652

ABSTRACT

Single-cell RNA sequencing (scRNA-seq) is currently one of the most powerful techniques available to study the transcriptional response of thousands of cells to an external perturbation. Here, we perform a pseudotime analysis of SARS-CoV-2 infection using publicly available scRNA-seq data from human bronchial epithelial cells and colon and ileum organoids. Our results reveal that, for most genes, the transcriptional response to SARS-CoV-2 infection follows a non-linear pattern characterized by an initial and a final down-regulatory phase separated by an intermediate up-regulatory stage. A correlation analysis of transcriptional profiles suggests a common mechanism regulating the mRNA levels of most genes. Interestingly, genes encoded in the mitochondria or involved in translation exhibited distinct pseudotime profiles. To explain our results, we propose a simple model where nuclear export inhibition of nsp1-sensitive transcripts will be sufficient to explain the transcriptional shutdown of SARS-CoV-2 infected cells.


Subject(s)
COVID-19 , Humans , COVID-19/genetics , Data Analysis , SARS-CoV-2/genetics , RNA, Messenger/genetics , Epithelial Cells
8.
Front Immunol ; 13: 896958, 2022.
Article in English | MEDLINE | ID: covidwho-2123410

ABSTRACT

Vaccines can prevent many millions of illnesses against infectious diseases and save numerous lives every year. However, traditional vaccines such as inactivated viral and live attenuated vaccines cannot adapt to emerging pandemics due to their time-consuming development. With the global outbreak of the COVID-19 epidemic, the virus continues to evolve and mutate, producing mutants with enhanced transmissibility and virulence; the rapid development of vaccines against such emerging global pandemics becomes more and more critical. In recent years, mRNA vaccines have been of significant interest in combating emerging infectious diseases due to their rapid development and large-scale production advantages. However, their development still suffers from many hurdles such as their safety, cellular delivery, uptake, and response to their manufacturing, logistics, and storage. More efforts are still required to optimize the molecular designs of mRNA molecules with increased protein expression and enhanced structural stability. In addition, a variety of delivery systems are also needed to achieve effective delivery of vaccines. In this review, we highlight the advances in mRNA vaccines against various infectious diseases and discuss the molecular design principles and delivery systems of associated mRNA vaccines. The current state of the clinical application of mRNA vaccine pipelines against various infectious diseases and the challenge, safety, and protective effect of associated vaccines are also discussed.


Subject(s)
COVID-19 , Communicable Diseases, Emerging , COVID-19/prevention & control , Communicable Diseases, Emerging/prevention & control , Humans , RNA, Messenger/genetics , Technology , Vaccination , Vaccines, Attenuated , Vaccines, Synthetic , mRNA Vaccines
9.
Hum Genomics ; 16(1): 59, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2119172

ABSTRACT

BACKGROUND: AU-rich elements (AREs) are located in the 3'UTRs of 22% of human mRNAs, including most transiently expressed inflammatory mediators. By default, AREs mark mRNAs for decay and translational inhibition, but this activity can be temporarily inhibited in case of infection to allow the onset of inflammation. Morbidity and mortality in COVID-19 patients have been associated with dysregulated inflammation, a process that may include aberrant ARE activity. RESULTS: RNA-seq data from available transcriptomic studies were analyzed to investigate a possible differential expression of mRNAs that contain AREs in the context of SARS-CoV-2 infections. ARE-mRNAs turned out to be significantly overrepresented among the upregulated mRNAs after SARS-CoV-2 infection (up to 42%). In contrast, ARE-mRNAs were underrepresented (16%) in the downregulated group. Consequently, at a global scale, ARE-mRNAs are significantly more upregulated after SARS-CoV-2 infection compared to non-ARE mRNAs. This observation was apparent in lung cell line models such as A549 and Calu-3 and with infections with other respiratory viruses and cell lines. Most importantly, at the clinical level, the elevated ARE-mRNA response appeared strongest in blood cells of COVID-19 patients with mild disease. It diminished with disease severity and was least apparent in patients in need of intubation and respiratory-related death. Gene function and clustering analysis suggest that the ARE-response is rather global and the upregulated ARE-mRNAs in patients with mild disease do not particularly cluster in specific functional groups. CONCLUSIONS: Compared to the rest of the transcriptome, ARE-containing mRNAs are preferentially upregulated in response to viral infections at a global level. In the context of COVID-19, they are most upregulated in mild disease. Due to their large number, their levels measured by RNA-seq may provide a reliable indication of COVID-19 severity.


Subject(s)
COVID-19 , Humans , RNA, Messenger/genetics , RNA, Messenger/metabolism , COVID-19/genetics , Up-Regulation/genetics , SARS-CoV-2 , Inflammation
10.
Sci Adv ; 8(45): eabp9961, 2022 11 11.
Article in English | MEDLINE | ID: covidwho-2119401

ABSTRACT

Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here, we investigated responses to coronavirus disease 2019 (COVID-19) mRNA vaccination via high-temporal resolution blood transcriptome profiling. The first vaccine dose elicited modest interferon and adaptive immune responses, which peaked on days 2 and 5, respectively. The second vaccine dose, in contrast, elicited sharp day 1 interferon, inflammation, and erythroid cell responses, followed by a day 5 plasmablast response. Both post-first and post-second dose interferon signatures were associated with the subsequent development of antibody responses. Yet, we observed distinct interferon response patterns after each of the doses that may reflect quantitative or qualitative differences in interferon induction. Distinct interferon response phenotypes were also observed in patients with COVID-19 and were associated with severity and differences in duration of intensive care. Together, this study also highlights the benefits of adopting high-frequency sampling protocols in profiling vaccine-elicited immune responses.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , COVID-19/prevention & control , RNA, Messenger/genetics , Vaccines, Synthetic , Interferons
11.
J Interferon Cytokine Res ; 42(11): 592-593, 2022 11.
Article in English | MEDLINE | ID: covidwho-2117093

ABSTRACT

Recently, messenger ribonucleic acid (mRNA) vaccine research and development became a hotspot in the field of prevention and treatment of Corona Virus Disease 2019 (COVID-19) and some other disorders. mRNA vaccine shows many advantages over other vaccines, including cost-effectiveness, safety, and rapid optimization of antigen-specific sequences and shorter development cycle. Cancer progression is significantly associated with immune response, and mRNA vaccine also shows obvious advantages for cancer immunotherapy. In this study, we briefly summarize the recent advances and discuss the perspectives on tumor mRNA vaccine development; particularly, these findings pave an avenue for effective cancer prevention and treatment.


Subject(s)
COVID-19 , Cancer Vaccines , Neoplasms , Humans , COVID-19/prevention & control , Cancer Vaccines/genetics , Neoplasms/genetics , Neoplasms/prevention & control , RNA, Messenger/genetics
12.
Nat Med ; 28(11): 2273-2287, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2116990

ABSTRACT

Messenger RNA (mRNA) is an emerging class of therapeutic agent for the prevention and treatment of a wide range of diseases. The recent success of the two highly efficacious mRNA vaccines produced by Moderna and Pfizer-BioNTech to protect against COVID-19 highlights the huge potential of mRNA technology for revolutionizing life science and medical research. Challenges related to mRNA stability and immunogenicity, as well as in vivo delivery and the ability to cross multiple biological barriers, have been largely addressed by recent progress in mRNA engineering and delivery. In this Review, we present the latest advances and innovations in the growing field of mRNA nanomedicine, in the context of ongoing clinical translation and future directions to improve clinical efficacy.


Subject(s)
COVID-19 , Nanomedicine , Humans , RNA, Messenger/genetics , Proteins
13.
Sci Rep ; 12(1): 19224, 2022 Nov 10.
Article in English | MEDLINE | ID: covidwho-2116718

ABSTRACT

Vaccination is widely considered the most effective preventative strategy to protect against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. An individual's exercise habits, and physical fitness have been shown to impact the immune response following vaccination using traditional vaccine platforms, but their effects are not well characterized following administration of newer vaccination technology (mRNA vaccines). We investigated these effects on the magnitude of antibody responses following SARS-CoV-2 mRNA vaccination while accounting for known covariates (age, sex, time since vaccination, and the type of vaccine administered). Adults of varying fitness levels (18-65 years; N = 50) who had received either the Moderna or Pfizer SARS-CoV-2 mRNA vaccine between 2 weeks and 6 months prior, completed health history and physical activity questionnaires, had their blood drawn, body composition, cardiorespiratory fitness, and strength assessed. Multiple linear regressions assessed the effect of percent body fat, hand grip strength, cardiorespiratory fitness, and physical activity levels on the magnitude of receptor binding domain protein (RBD) and spike protein subunit 1 (S1) and 2 (S2) while accounting for known covariates. Body fat percentage was inversely associated with the magnitude of S1 (p = 0.006, ß = - 366.56), RBD (p = 0.003, ß = - 249.30), and S2 (p = 0.106, ß = - 190.08) antibodies present in the serum following SARS-CoV-2 mRNA vaccination. Given the increasing number of infections, variants, and the known waning effects of vaccination, future mRNA vaccinations such as boosters are encouraged to sustain immunity; reducing excess body fat may improve the efficacy of these vaccinations.


Subject(s)
COVID-19 , Viral Vaccines , Humans , Antibody Formation , COVID-19 Vaccines , SARS-CoV-2 , Hand Strength , COVID-19/prevention & control , Vaccination , Adipose Tissue , RNA, Messenger/genetics , Antibodies, Viral
14.
Theranostics ; 12(17): 7509-7531, 2022.
Article in English | MEDLINE | ID: covidwho-2114572

ABSTRACT

Lipid nanoparticles (LNPs) have been one of the most successful nano-delivery vehicles that enable efficient delivery of cytotoxic chemotherapy agents, antibiotics, and nucleic acid therapeutics. During the coronavirus disease (COVID-19) pandemic, LNP-based COVID-19 messenger RNA (mRNA) vaccines from Pfizer/BioNTech and Moderna have been successfully developed, resulting in global sales of $37 billion and $17.7 billion, respectively, in 2021. Based on this success, the development of multiple LNP-based RNA therapeutics is gaining momentum due to its potential in vaccines and therapeutics for various genetic diseases and cancers. Furthermore, imaging techniques can be utilized to evaluate the pharmacokinetics and pharmacodynamics (PK/PD) effects, which helps target discovery and accelerates the development of LNP-based mRNA therapies. A thorough introduction and explanation of the components of LNPs and its functions along with various production methods of formulating LNPs are provided in this review. Furthermore, recent advances in LNP-based RNA therapeutics in clinics and clinical trials are explored. Additionally, the evaluation of PK/PD of LNPs for RNA delivery and the current and potential roles in developing LNP-based mRNA pharmaceutics through imaging techniques will be discussed.


Subject(s)
COVID-19 , RNA , Humans , Lipids , COVID-19/therapy , RNA, Messenger/genetics
15.
Viral Immunol ; 35(9): 577-578, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2113169
16.
PLoS One ; 17(11): e0276697, 2022.
Article in English | MEDLINE | ID: covidwho-2112663

ABSTRACT

To characterize species of viral mRNA transcripts generated during respiratory syncytial virus (RSV) infection, human fibroblast-like MRC-5 lung cells were infected with subgroup A RSV for 6, 16 and 24 hours. In addition, we characterised the viral transcriptome in infected Calu-3 lung epithelial cells at 48 hours post infection. Total RNA was harvested and polyadenylated mRNA was enriched and sequenced by direct RNA sequencing using an Oxford nanopore device. This platform yielded over 450,000 direct mRNA transcript reads which were mapped to the viral genome and analysed to determine the relative mRNA levels of viral genes using our in-house ORF-centric pipeline. We examined the frequency of polycistronic readthrough mRNAs were generated and assessed the length of the polyadenylated tails for each group of transcripts. We show a general but non-linear decline in gene transcript abundance across the viral genome, as predicted by the model of RSV gene transcription. However, the decline in transcript abundance is not uniform. The polyadenylate tails generated by the viral polymerase are similar in length to those generated by the host polyadenylation machinery and broadly declined in length for most transcripts as the infection progressed. Finally, we observed that the steady state abundance of transcripts with very short polyadenylate tails less than 20 nucleotides is less for N, SH and G transcripts in both cell lines compared to NS1, NS2, P, M, F and M2 which may reflect differences in mRNA stability and/or translation rates within and between the cell lines.


Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Humans , RNA, Messenger/genetics , RNA, Viral/genetics , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus Infections/genetics , Sequence Analysis, RNA
18.
Int J Infect Dis ; 111: 310-312, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-2113726

ABSTRACT

OBJECTIVES: Facial nerve palsy (or Bell's palsy) has occasionally been reported following the administration of coronavirus disease 2019 (COVID-19) mRNA vaccines (BNT162b2 and mRNA-1273). Our study investigated such cases using a large self-reporting database from the USA (Vaccine Adverse Event Reporting System [VAERS]). METHODS: A disproportionality analysis, adjusted for age and sex, was conducted for VAERS reports from individuals who were vaccinated at the age of 18 years or over, between January 2010 and April 2021. RESULTS: The analysis revealed that the adverse events following immunization (AEFI) of facial nerve palsy, after administration of COVID-19 mRNA vaccines, was significantly highly reported, both for BNT162b2 (reporting odds ratio [ROR] 1.84; 95% confidence interval [CI] 1.65-2.06) and mRNA-1273 (ROR 1.54; 95% CI 1.39-1.70). These levels were comparable to that following influenza vaccination reported before the COVID-19 pandemic (ROR 2.04; 95% CI 1.76-2.36). CONCLUSIONS: Our pharmacovigilance study results suggest that the incidence of facial nerve palsy as a non-serious AEFI may be lower than, or equivalent to, that for influenza vaccines. This information might be of value in the context of promoting worldwide vaccination, but needs to be validated in future observational studies.


Subject(s)
Bell Palsy , COVID-19 , Influenza Vaccines , Adolescent , Adult , Adverse Drug Reaction Reporting Systems , Bell Palsy/epidemiology , COVID-19 Vaccines/adverse effects , Facial Nerve , Humans , Influenza Vaccines/adverse effects , Pandemics , Paralysis , RNA, Messenger/genetics , SARS-CoV-2 , Young Adult
19.
Cornea ; 41(12): 1559-1563, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2107628

ABSTRACT

PURPOSE: The aim of this study was to analyze the presence of the SARS-CoV-2 virus in the corneal tissue of asymptomatic deceased novel coronavirus disease 2019 (COVID-19) patients. METHODS: This was a cross-sectional study performed at a tertiary eye hospital. All corneas of the deceased asymptomatic donors who tested positive for SARS-CoV-2 on a nasopharyngeal swab at the time of corneal tissue harvesting were included in the study. Histopathological examination and immunohistochemistry were performed. mRNA in situ hybridization for SARS-CoV-2 was performed in all specimens that showed positive immunostaining. The main outcome measure was the presence of SARS-CoV-2 virus in the corneal tissues. RESULTS: Twenty-two corneal tissues of 11 donors were analyzed. The mean age was 72.2 ± 14.2 years. On histological examination, no signs of inflammation or any other abnormalities were detected in the cornea and adjacent bulbar conjunctiva. Immunohistochemistry revealed faint to moderate cytoplasmic staining in the basal layer of the corneal epithelium in 8 specimens from 5 patients. None of the specimens with positive immunostaining showed the presence of SARS-CoV-2 mRNA. CONCLUSIONS: In line with previous studies , our study also reflects the absence of SARS-CoV-2 viral mRNA in corneal tissues of clinically asymptomatic deceased COVID-19 donors, thereby indicating a probable low risk of transmission of the SARS-CoV-2 virus through the transplantation of corneas from donors who tested positive for, but were asymptomatic for COVID-19. In addition, further studies on the subject should include histopathological examination because of the false positive and negative rates of molecular tests.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Middle Aged , Aged , Aged, 80 and over , COVID-19/diagnosis , Cross-Sectional Studies , Tissue Donors , Cornea , RNA, Messenger/genetics
20.
Front Immunol ; 13: 1018961, 2022.
Article in English | MEDLINE | ID: covidwho-2109768

ABSTRACT

Synthetic mRNA technologies represent a versatile platform that can be used to develop advanced drug products. The remarkable speed with which vaccine development programs designed and manufactured safe and effective COVID-19 vaccines has rekindled interest in mRNA technology, particularly for future pandemic preparedness. Although recent R&D has focused largely on advancing mRNA vaccines and large-scale manufacturing capabilities, the technology has been used to develop various immunotherapies, gene editing strategies, and protein replacement therapies. Within the mRNA technologies toolbox lie several platforms, design principles, and components that can be adapted to modulate immunogenicity, stability, in situ expression, and delivery. For example, incorporating modified nucleotides into conventional mRNA transcripts can reduce innate immune responses and improve in situ translation. Alternatively, self-amplifying RNA may enhance vaccine-mediated immunity by increasing antigen expression. This review will highlight recent advances in the field of synthetic mRNA therapies and vaccines, and discuss the ongoing global efforts aimed at reducing vaccine inequity by establishing mRNA manufacturing capacity within Africa and other low- and middle-income countries.


Subject(s)
COVID-19 , Vaccines , Humans , RNA, Messenger/genetics , COVID-19 Vaccines , COVID-19/prevention & control , Technology
SELECTION OF CITATIONS
SEARCH DETAIL