2,797 results on '"Ooi EE"'
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2. A prM mutation that attenuates dengue virus replication in human cells enhances midgut infection in mosquitoes.
- Author
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Choi ANX, Siriphanitchakorn T, Choy MM, Ooi JSG, Manuel M, Tan HC, Lin LZ, Yap X, Gubler DJ, and Ooi EE
- Subjects
- Animals, Humans, Dengue virology, Dengue transmission, Phylogeny, Cell Line, Protein Biosynthesis, Dengue Virus genetics, Dengue Virus physiology, Virus Replication genetics, Mutation genetics, Aedes virology
- Abstract
Dengue viruses (DENVs), like all viruses, evolve to perpetuate transmission of their species in their hosts. However, how DENV genetics influences dengue disease outbreaks remains poorly understood. Here, we examined isolates of the South Pacific dengue virus type 2 (DENV-2) that emerged in the 1970s and caused major dengue outbreaks in islands in this region until it reached Tonga, where only a few mild cases were reported. Phylogenetically, the DENV-2 strain isolated in Tonga segregated into a clade different from those clades infecting populations in other South Pacific islands. We found that this epidemiological observation could be explained by a single histidine-to-arginine substitution in position 86 of the premembrane (prM) protein of the Tonga DENV-2 strain. This mutation attenuated viral protein translation in mammalian cells but not in midgut cells of the mosquito vector Aedes aegypti . In mammalian cells, the prM mutation resulted in reduced translation of the viral genome and subsequent reduced virus replication. In contrast, in mosquito midgut cells, the prM mutation conferred a selective infection advantage, possibly because of the positively charged arginine residue introduced by the mutation. These findings provide molecular insights into the year-long silent transmission of attenuated DENV-2 in Tonga during the 1970s dengue outbreak in the South Pacific.
- Published
- 2024
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3. A natural human cell-adapted dengue type 3 virus strain.
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Ng WC, Lin L, Siriphanitchakorn T, Jiang MKX, Tan HC, and Ooi EE
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- Humans, Cell Line, Animals, Dengue Virus classification, Dengue Virus genetics, Dengue virology
- Abstract
Competing Interests: The authors declare no conflict of interest.
- Published
- 2024
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4. Publisher Correction: Correlates of protection against symptomatic SARS-CoV-2 in vaccinated children.
- Author
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Zhong Y, Kang AYH, Tay CJX, Li HE, Elyana N, Tan CW, Yap WC, Lim JME, Le Bert N, Chan KR, Ong EZ, Low JG, Shek LP, Tham EH, and Ooi EE
- Published
- 2024
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5. Non-line-of-sight methodology for high-speed wireless optical communication in highly turbid water
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Sun, Xiaobin, Kong, Meiwei, Alkhazragi, Omar, Shen, Chao, Ooi, Ee-Ning, Zhang, Xinyu, Buttner, Ulrich, Ng, Tien Khee, and Ooi, Boon S.
- Published
- 2020
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6. Impact of high-risk EBV strains on nasopharyngeal carcinoma gene expression.
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Lim CY, Ng GWY, Goh CK, Lee MKC, Cheong I, Ooi EE, Liu J, West RB, Loh KS, and Tay JK
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- Humans, Viral Proteins genetics, Viral Proteins metabolism, Male, Polymorphism, Single Nucleotide, Female, Gene Expression Regulation, Neoplastic, Nasopharyngeal Carcinoma virology, Nasopharyngeal Carcinoma genetics, Herpesvirus 4, Human genetics, Herpesvirus 4, Human isolation & purification, Nasopharyngeal Neoplasms virology, Nasopharyngeal Neoplasms genetics, Epstein-Barr Virus Infections complications, Epstein-Barr Virus Infections virology
- Abstract
Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr Virus infection (EBV). Despite ubiquitous EBV infection worldwide, NPC displays a unique geographical distribution in Southern China and Southeast Asia. This observed phenomenon can be attributed to the interplay of different strains of EBV infection with host genetics and environmental factors. Polymorphisms on the EBV BALF2 gene have been shown to influence risk of nasopharyngeal carcinoma (NPC). Notably, two non-synonymous EBV polymorphisms (162476T>C, 163364C>T) account for majority of NPC risk in endemic regions. These polymorphisms confer amino acid changes (I1613V, V317M) within the BALF2 protein. However, their impact on NPC tumor biology is unknown. We evaluated the distribution of BALF2 risk polymorphisms in five independent genomic datasets comprising 351 NPC clinical samples, confirming the high prevalence of high-risk EBV strains in NPC. Importantly, we observed two biologically distinct groups of tumors based on their gene expression profiles when grouped by their EBV risk strains. NPC tumors with the V317M substitution demonstrated increased proliferation processes including cell cycle (NES = 1.71, p = 5.64x10
-24 ) and keratinization (NES = 2.42, p = 6.95x10-17 ). In contrast, NPC tumors without the V317M substitution demonstrated increased immune-related processes, including cell activation (NES = 1.85, p = 8.29x10-31 ), myeloid leukocyte activation (NES = 2.16, p = 6.51x10-24 ) and leukocyte mediated immunity (NES = 1.99, p = 1.05x10-23 ). These findings provide further insight on the influence of BALF2 variants on NPC tumor biology. EBV risk strains may have the potential to define biologically important groups in NPC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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7. Is a therapeutic dengue monoclonal antibody on the way?
- Author
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Ooi EE and Chan YF
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- Humans, Antibodies, Monoclonal therapeutic use, Dengue immunology, Dengue drug therapy, Antibodies, Viral therapeutic use, Dengue Virus immunology
- Abstract
Competing Interests: EEO collaborated with Visterra, which developed VIS513 during the pre-clinical stages of development but was not involved with the clinical trial. EEO has also served in advisory capacities to Takeda on dengue vaccine, and Janssen Pharmaceuticals and Novartis on dengue therapeutics. YFZC declared no competing interests.
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- 2024
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8. Electron transport chain capacity expands yellow fever vaccine immunogenicity.
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Mok DZ, Tng DJ, Yee JX, Chew VS, Tham CY, Ooi JS, Tan HC, Zhang SL, Lin LZ, Ng WC, Jeeva LL, Murugayee R, Goh KK, Lim TP, Cui L, Cheung YB, Ong EZ, Chan KR, Ooi EE, and Low JG
- Subjects
- Humans, Immunogenicity, Vaccine, Yellow Fever prevention & control, Yellow Fever immunology, Adult, Male, Female, Yellow Fever Vaccine immunology, Yellow Fever Vaccine administration & dosage, Metformin pharmacology, Antibodies, Neutralizing immunology, Antibodies, Neutralizing blood, Antibodies, Viral blood, Antibodies, Viral immunology
- Abstract
Vaccination has successfully controlled several infectious diseases although better vaccines remain desirable. Host response to vaccination studies have identified correlates of vaccine immunogenicity that could be useful to guide development and selection of future vaccines. However, it remains unclear whether these findings represent mere statistical correlations or reflect functional associations with vaccine immunogenicity. Functional associations, rather than statistical correlates, would offer mechanistic insights into vaccine-induced adaptive immunity. Through a human experimental study to test the immunomodulatory properties of metformin, an anti-diabetic drug, we chanced upon a functional determinant of neutralizing antibodies. Although vaccine viremia is a known correlate of antibody response, we found that in healthy volunteers with no detectable or low yellow fever 17D viremia, metformin-treated volunteers elicited higher neutralizing antibody titers than placebo-treated volunteers. Transcriptional and metabolomic analyses collectively showed that a brief course of metformin, started 3 days prior to YF17D vaccination and stopped at 3 days after vaccination, expanded oxidative phosphorylation and protein translation capacities. These increased capacities directly correlated with YF17D neutralizing antibody titers, with reduced reactive oxygen species response compared to placebo-treated volunteers. Our findings thus demonstrate a functional association between cellular respiration and vaccine-induced humoral immunity and suggest potential approaches to enhancing vaccine immunogenicity., (© 2024. The Author(s).)
- Published
- 2024
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9. Secreted dengue virus NS1 from infection is predominantly dimeric and in complex with high-density lipoprotein.
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Chew BLA, Ngoh ANQ, Phoo WW, Chan KWK, Ser Z, Tulsian NK, Lim SS, Weng MJG, Watanabe S, Choy MM, Low J, Ooi EE, Ruedl C, Sobota RM, Vasudevan SG, and Luo D
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- Animals, Chlorocebus aethiops, Mice, Humans, Vero Cells, Apolipoprotein A-I metabolism, Apolipoprotein A-I chemistry, Protein Multimerization, Cryoelectron Microscopy, Viral Nonstructural Proteins metabolism, Viral Nonstructural Proteins chemistry, Viral Nonstructural Proteins genetics, Dengue Virus genetics, Dengue Virus metabolism, Lipoproteins, HDL metabolism, Dengue virology, Dengue metabolism
- Abstract
Severe dengue infections are characterized by endothelial dysfunction shown to be associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and biotherapeutic target. To uncover the biologically relevant structure of sNS1, we obtained infection-derived sNS1 (isNS1) from dengue virus (DENV)-infected Vero cells through immunoaffinity purification instead of recombinant sNS1 (rsNS1) overexpressed in insect or mammalian cell lines. We found that isNS1 appeared as an approximately 250 kDa complex of NS1 and ApoA1 and further determined the cryoEM structures of isNS1 and its complex with a monoclonal antibody/Fab. Indeed, we found that the major species of isNS1 is a complex of the NS1 dimer partially embedded in a high-density lipoprotein (HDL) particle. Crosslinking mass spectrometry studies confirmed that the isNS1 interacts with the major HDL component ApoA1 through interactions that map to the NS1 wing and hydrophobic domains. Furthermore, our studies demonstrated that the sNS1 in sera from DENV-infected mice and a human patient form a similar complex as isNS1. Our results report the molecular architecture of a biological form of sNS1, which may have implications for the molecular pathogenesis of dengue., Competing Interests: BC, AN, WP, KC, ZS, NT, SL, MW, SW, MC, JL, EO, CR, RS, SV, DL No competing interests declared, (© 2023, Chew, Ngoh, Phoo et al.)
- Published
- 2024
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10. Correlates of protection against symptomatic SARS-CoV-2 in vaccinated children.
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Zhong Y, Kang AYH, Tay CJX, Li HE, Elyana N, Tan CW, Yap WC, Lim JME, Le Bert N, Chan KR, Ong EZ, Low JG, Shek LP, Tham EH, and Ooi EE
- Subjects
- Humans, Child, Child, Preschool, Female, Male, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, Memory B Cells immunology, Spike Glycoprotein, Coronavirus immunology, Cohort Studies, Immunization, Secondary, Immunoglobulin G immunology, Immunoglobulin G blood, COVID-19 immunology, COVID-19 prevention & control, SARS-CoV-2 immunology, Antibodies, Neutralizing immunology, Antibodies, Neutralizing blood, Antibodies, Viral immunology, Antibodies, Viral blood, BNT162 Vaccine immunology, BNT162 Vaccine administration & dosage, T-Lymphocytes immunology, Vaccination
- Abstract
The paucity of information on longevity of vaccine-induced immune responses and uncertainty of the correlates of protection hinder the development of evidence-based COVID-19 vaccination policies for new birth cohorts. Here, to address these knowledge gaps, we conducted a cohort study of healthy 5-12-year-olds vaccinated with BNT162b2. We serially measured binding and neutralizing antibody titers (nAbs), spike-specific memory B cell (MBC) and spike-reactive T cell responses over 1 year. We found that children mounted antibody, MBC and T cell responses after two doses of BNT162b2, with higher antibody and T cell responses than adults 6 months after vaccination. A booster (third) dose only improved antibody titers without impacting MBC and T cell responses. Among children with hybrid immunity, nAbs and T cell responses were highest in those infected after two vaccine doses. Binding IgG titers, MBC and T cell responses were predictive, with T cells being the most important predictor of protection against symptomatic infection before hybrid immunity; nAbs only correlated with protection after hybrid immunity. The stable MBC and T cell responses over time suggest sustained protection against symptomatic SARS-CoV-2 infection, even when nAbs wane. Booster vaccinations do not confer additional immunological protection to healthy children., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2024
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11. The α-dystroglycan N-terminus is a broad-spectrum antiviral agent against SARS-CoV-2 and enveloped viruses.
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Bigotti MG, Klein K, Gan ES, Anastasina M, Andersson S, Vapalahti O, Katajisto P, Erdmann M, Davidson AD, Butcher SJ, Collinson I, Ooi EE, Balistreri G, Brancaccio A, and Yamauchi Y
- Subjects
- Mice, Animals, Humans, Dystroglycans, Pandemics, Escherichia coli, Mice, Transgenic, Antiviral Agents pharmacology, SARS-CoV-2, COVID-19
- Abstract
The COVID-19 pandemic has shown the need to develop effective therapeutics in preparedness for further epidemics of virus infections that pose a significant threat to human health. As a natural compound antiviral candidate, we focused on α-dystroglycan, a highly glycosylated basement membrane protein that links the extracellular matrix to the intracellular cytoskeleton. Here we show that the N-terminal fragment of α-dystroglycan (α-DGN), as produced in E. coli in the absence of post-translational modifications, blocks infection of SARS-CoV-2 in cell culture, human primary gut organoids and the lungs of transgenic mice expressing the human receptor angiotensin I-converting enzyme 2 (hACE2). Prophylactic and therapeutic administration of α-DGN reduced SARS-CoV-2 lung titres and protected the mice from respiratory symptoms and death. Recombinant α-DGN also blocked infection of a wide range of enveloped viruses including the four Dengue virus serotypes, influenza A virus, respiratory syncytial virus, tick-borne encephalitis virus, but not human adenovirus, a non-enveloped virus in vitro. This study establishes soluble recombinant α-DGN as a broad-band, natural compound candidate therapeutic against enveloped viruses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Maria Giulia Bigotti, Katja Klein, Andrea Brancaccio and Yohei Yamauchi have patent #GB 2315095.6. issued to University of Bristol. Eng Eong Ooi has served in various advisory capacities on dengue vaccines for Sanofi Pasteur and MSD and served on the advisory board on dengue vaccines and antiviral drugs for Takeda. All other authors declare that they have no competing interests If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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12. Impulsiveness, postprandial blood glucose, and glucoregulation affect measures of behavioral flexibility
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Riby, Leigh M., Lai Teik Ong, Derek, Azmie, Nurulnadia Binti Mohamad, Ooi, Ee Lyn, Regina, Caroline, Yeo, Eugene Ki Wai, Massa, Jacqueline, and Aquili, Luca
- Published
- 2017
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13. Proceedings of the 6th Asia Dengue Summit, June 2023.
- Author
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Srisawat N, Gubler DJ, Pangestu T, Limothai U, Thisyakorn U, Ismail Z, Goh D, Capeding MR, Bravo L, Yoksan S, Tantawichien T, Hadinegoro SR, Rafiq K, Picot VS, and Ooi EE
- Subjects
- Humans, Thailand, Public Health, World Health Organization, Asia, Southeastern epidemiology, Travel, Dengue epidemiology, Dengue prevention & control
- Abstract
The 6th Asia Dengue Summit (ADS) themed "Road Map to Zero Dengue Death" was held in Thailand from 15th-16th June 2023. The summit was hosted by Tropical Medicine Cluster, Chulalongkorn University, Bangkok, Thailand in conjunction with Queen Saovabha Memorial Institute, The Thai Red Cross Society; Faculty of Tropical Medicine, Mahidol University; and the Ministry of Public Health. The 6th ADS was convened by Asia Dengue Voice and Action (ADVA); Global Dengue and Aedes Transmitted Diseases Consortium (GDAC); Southeast Asian Ministers of Education Tropical Medicine and Public Health Network (SEAMEO TROPMED); Fondation Mérieux (FMx) and the International Society for Neglected Tropical Diseases (ISNTD). Dengue experts from academia and research, and representatives from the Ministries of Health, Regional and Global World Health Organization (WHO) and International Vaccine Institute (IVI) participated in the three-day summit. With more than 51 speakers and 451 delegates from over 24 countries, 10 symposiums, and 2 full days, the 6th ADS highlighted the growing threat of dengue and its antigenic evolution, flagged the urgent need to overcome vaccine hesitancy and misinformation crisis, and focused on dengue control policies, newer diagnostics, therapeutics and vaccines, travel-associated dengue, and strategies to improve community involvement., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Srisawat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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14. Race against dengue.
- Author
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Kwek SS and Ooi EE
- Subjects
- Humans, Viremia, Kinetics, Antibodies, Viral, Dengue epidemiology, Dengue Virus
- Abstract
Understanding the kinetics of dengue viruses in the bloodstream can provide insights into the clinical outcomes of the disease., Competing Interests: SK, EO No competing interests declared, (© 2024, Kwek and Ooi.)
- Published
- 2024
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15. Repurposing of Zika virus live-attenuated vaccine (ZIKV-LAV) strains as oncolytic viruses targeting human glioblastoma multiforme cells.
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Victorio CBL, Novera W, Ganasarajah A, Ong J, Thomas M, Wu J, Toh HSY, Sun AX, Ooi EE, and Chacko AM
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- Humans, Vaccines, Attenuated, Neoplasm Recurrence, Local therapy, Zika Virus physiology, Oncolytic Viruses, Zika Virus Infection prevention & control, Glioblastoma therapy, Oncolytic Virotherapy
- Abstract
Glioblastoma multiforme (GBM) is the most common malignant primary brain cancer affecting the adult population. Median overall survival for GBM patients is poor (15 months), primarily due to high rates of tumour recurrence and the paucity of treatment options. Oncolytic virotherapy is a promising treatment alternative for GBM patients, where engineered viruses selectively infect and eradicate cancer cells by inducing cell lysis and eliciting robust anti-tumour immune response. In this study, we evaluated the oncolytic potency of live-attenuated vaccine strains of Zika virus (ZIKV-LAV) against human GBM cells in vitro. Our findings revealed that Axl and integrin α
v β5 function as cellular receptors mediating ZIKV-LAV infection in GBM cells. ZIKV-LAV strains productively infected and lysed human GBM cells but not primary endothelia and terminally differentiated neurons. Upon infection, ZIKV-LAV mediated GBM cell death via apoptosis and pyroptosis. This is the first in-depth molecular dissection of how oncolytic ZIKV infects and induces death in tumour cells., (© 2024. The Author(s).)- Published
- 2024
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16. High-speed colour-converting photodetector with all-inorganic CsPbBr3 perovskite nanocrystals for ultraviolet light communication
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Kang, Chun Hong, Dursun, Ibrahim, Liu, Guangyu, Sinatra, Lutfan, Sun, Xiaobin, Kong, Meiwei, Pan, Jun, Maity, Partha, Ooi, Ee-Ning, Ng, Tien Khee, Mohammed, Omar F., Bakr, Osman M., and Ooi, Boon S.
- Published
- 2019
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17. Ooi et al (2023) - Supplementary materials.docx
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Ooi, Ee Cheng, XIANG, RUIDONG, Chamberlain, Amanda, and GODDARD, MICHAEL
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Animal production not elsewhere classified - Abstract
Supplementary materials for a published paper: Archetypal clustering reveals physiological mechanisms linking milk yield and fertility in dairy cattle.
- Published
- 2023
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18. Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells.
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Liao KC, Xie X, Sundstrom AKB, Lim XN, Tan KK, Zhang Y, Zou J, Bifani AM, Poh HX, Chen JJ, Ng WC, Lim SY, Ooi EE, Sessions OM, Tay Y, Shi PY, Huber RG, and Wan Y
- Subjects
- Humans, RNA, Viral genetics, 3' Untranslated Regions, Virus Replication, Antiviral Agents, Dyneins genetics, Dyneins metabolism, Zika Virus genetics, Zika Virus Infection genetics, Dengue Virus genetics, Dengue Virus metabolism, Dengue genetics
- Abstract
Background: Identifying host factors is key to understanding RNA virus pathogenicity. Besides proteins, RNAs can interact with virus genomes to impact replication., Results: Here, we use proximity ligation sequencing to identify virus-host RNA interactions for four strains of Zika virus (ZIKV) and one strain of dengue virus (DENV-1) in human cells. We find hundreds of coding and non-coding RNAs that bind to DENV and ZIKV viruses. Host RNAs tend to bind to single-stranded regions along the virus genomes according to hybridization energetics. Compared to SARS-CoV-2 interactors, ZIKV-interacting host RNAs tend to be downregulated upon virus infection. Knockdown of several short non-coding RNAs, including miR19a-3p, and 7SK RNA results in a decrease in viral replication, suggesting that they act as virus-permissive factors. In addition, the 3'UTR of DYNLT1 mRNA acts as a virus-restrictive factor by binding to the conserved dumbbell region on DENV and ZIKV 3'UTR to decrease virus replication. We also identify a conserved set of host RNAs that interacts with DENV, ZIKV, and SARS-CoV-2, suggesting that these RNAs are broadly important for RNA virus infection., Conclusions: This study demonstrates that host RNAs can impact virus replication in permissive and restrictive ways, expanding our understanding of host factors and RNA-based gene regulation during viral pathogenesis., (© 2023. The Author(s).)
- Published
- 2023
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19. Minding the "T"s beyond the "B"s: Shaping vaccines for future pandemics.
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Kalimuddin S and Ooi EE
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- Humans, COVID-19 Vaccines, Pandemics prevention & control, SARS-CoV-2, Viral Vaccines, COVID-19 epidemiology, COVID-19 prevention & control, Vaccines
- Abstract
The COVID-19 pandemic has accelerated the development of vaccines for viral infections. However, a failure to integrate T cell immunity as a determinant of vaccine efficacy could curtail advancement of newer vaccines for pandemic preparedness., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: EEO is a member of the Advisory Board of Arcturus Therapeutics, and has served in advisory capacities on dengue for Sanofi Pasteur, Takeda, Johnson & Johnson and Novartis. SK has served as an advisor on dengue for Takeda and Johnson & Johnson., (Copyright: © 2023 Kalimuddin, Ooi. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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20. Inactivated Zika virus vaccine and the complexity of flavivirus antigenicity.
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Low JG and Ooi EE
- Subjects
- Humans, Vaccines, Inactivated, Antigens, Viral, Antibodies, Viral, Zika Virus, Zika Virus Infection epidemiology, Zika Virus Infection prevention & control, Viral Vaccines
- Abstract
Competing Interests: We declare no competing interests.
- Published
- 2023
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21. A tribute to the late Emeritus Professor Chan Soh Ha.
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Ooi EE
- Published
- 2023
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22. The Dairy Fertility Investigator: Blogging as a digital extension platform for agriculture
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Ooi, Ee Cheng, Campbell, Joanne, OSullivan, Ross, and Chaplin, Sarah
- Published
- 2015
23. Novel antiviral host factor, TNK1, regulates IFN signaling through serine phosphorylation of STAT1
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Ooi, Ee Lyn, Chan, Stephanie T., Cho, Noell E., Wilkins, Courtney, Woodward, Jessica, Li, Meng, Kikkawa, Ushio, Tellinghuisen, Timothy, Gale, Michael, and Saito, Takeshi
- Published
- 2014
24. Erratum for the Review "Insights into dengue immunity from vaccine trials".
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Ooi EE and Kalimuddin S
- Published
- 2023
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25. Insights into dengue immunity from vaccine trials.
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Ooi EE and Kalimuddin S
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- Humans, Public Health, Immunity, Cellular, Dengue prevention & control
- Abstract
The quest for an effective dengue vaccine has culminated in two approved vaccines and another that has completed phase 3 clinical trials. However, shortcomings exist in each, suggesting that the knowledge on dengue immunity used to develop these vaccines was incomplete. Vaccine trial findings could refine our understanding of dengue immunity, because these are experimentally derived, placebo-controlled data. Results from these trials suggest that neutralizing antibody titers alone are insufficient to inform protection against symptomatic infection, implicating a role for cellular immunity in protection. These findings have relevance for both future dengue vaccine development and application of current vaccines for maximal public health benefit.
- Published
- 2023
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26. Hyperinflammatory Syndrome, Natural Killer Cell Function, and Genetic Polymorphisms in the Pathogenesis of Severe Dengue
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Vuong, NL, Cheung, K-W, Periaswamy, B, Vi, TT, Duyen, HTL, Leong, YS, Binte Hamis, ZN, Gregorova, M, Ooi, EE, Sessions, O, Rivino, L, and Yacoub, S
- Subjects
Killer Cells, Natural ,Infectious Diseases ,Polymorphism, Genetic ,Perforin ,Ferritins ,Immunology and Allergy ,Humans ,RNA ,Severe Dengue ,Biomarkers ,Granzymes ,Receptors, NK Cell Lectin-Like - Abstract
Background Severe dengue, characterized by shock and organ dysfunction, is driven by an excessive host immune response. We investigated the role of hyperinflammation in dengue pathogenesis. Methods Patients recruited into an observational study were divided into 3 plasma leak severity grades. Hyperinflammatory biomarkers were measured at 4 time points. Frequencies, activation, and cytotoxic potential of natural killer (NK) cells were analyzed by flow cytometry. RNA was extracted from sorted CD56+ NK cells and libraries were prepared using SMART-Seq and sequenced using HiSeq3000 (Illumina). Results Sixty-nine patients were included (grade 0, 42 patients; grade 1, 19 patients; grade 2, 8 patients). Patients with grade 2 leakage had higher biomarkers than grade 0, including higher peak ferritin levels (83.3% vs 45.2%) and H-scores (median, 148.5 vs 105.5). NK cells from grade 2 patients exhibited decreased expression of perforin and granzyme B and activation markers. RNA sequencing revealed 3 single-nucleotide polymorphisms in NK cell functional genes associated with more severe leakage—NK cell lectin-like receptor K1 gene (KLRK1) and perforin 1 (PRF1). Conclusions Features of hyperinflammation are associated with dengue severity, including higher biomarkers, impaired NK cell function, and polymorphisms in NK cell cytolytic function genes (KLRK1 and PRF1). Trials of immunomodulatory therapy in these patients is now warranted.
- Published
- 2022
27. Issues of Entering New Market and Ways to Overcome the Issues Company: F&N Holdings Berhad
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Faisal AlDeehani, Ooi Ee Jun, Ma Jia Qi, Tan Xiang Wen, Koay Xiem Chen, and Daisy Mui Hung Kee
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Politics ,Water company ,Scope (project management) ,Work (electrical) ,Core business ,General Medicine ,Business ,Marketing ,Annual turnover - Abstract
Solutions Resolve for Problem Encountered of Entering New Market in Fraser & Neave Holdings Bhd (F&NHB) F&NHB is among the oldest and most successful businesses in Singapore and Malaysia with core expertise and leadership in the food, beverage and other sectors. 135 years ago, two visionaries who are John Fraser and David Chalmers Neave formed The Singapore and Straits Aerated Water Company to produce carbonated soft drinks. This company eventually became one of the region’s food and beverage giants which is Fraser & Neave (F&N). Now, this company had been listed on Bursa Malaysia’s main board. F&NHB has an annual turnover in excess of RM 4 billion from its core business in the manufacture, sale and marketing of beverages and dairy products. In the present work, there are a problem encountered for entering new market of F&NHB according to our research. In fact, entering new market is a big challenge for every company because it represents the company must expand its business scope to make more profits. Before entering new market, F&NHB must determine the problems which will be faced in the future through analysing the political environment, economic environment, social and technology environment. Therefore, information is gathered to make the best decision for the market entry. Subsequently, solutions will be sought out and discussed to solve the issues which occurred in following new market through investigation. We will collect the data needed by referring the company website and other websites then analyse data to make the assignment completed.
- Published
- 2019
28. The impact of declining dairy fertility on calving patterns and farm systems: A case study from northern Victoria, Australia
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Ooi, Ee Cheng, primary, Stevenson, Mark A., additional, Beggs, David S., additional, Mansell, Peter D., additional, Pryce, Jennie E., additional, Murray, Alistair, additional, and Pyman, Michael F., additional
- Published
- 2021
- Full Text
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29. RNase2 is a possible trigger of acute-on-chronic inflammation leading to mRNA vaccine-associated cardiac complication.
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Ong EZ, Koh CWT, Tng DJH, Ooi JSG, Yee JX, Chew VSY, Leong YS, Gunasegaran K, Yeo CP, Oon LLE, Sim JXY, Chan KR, Low JG, and Ooi EE
- Subjects
- Humans, Cohort Studies, SARS-CoV-2 genetics, mRNA Vaccines, Cytokines, Inflammation, COVID-19 Vaccines adverse effects, COVID-19 prevention & control
- Abstract
Background: Post-mRNA vaccination-associated cardiac complication is a rare but life-threatening adverse event. Its risk has been well balanced by the benefit of vaccination-induced protection against severe COVID-19. As the rate of severe COVID-19 has consequently declined, future booster vaccination to sustain immunity, especially against infection with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, may encounter benefit-risk ratios that are less favorable than at the start of the COVID-19 vaccination campaign. Understanding the pathogenesis of rare but severe vaccine-associated adverse events to minimize its risk is thus urgent., Methods: Here, we report a serendipitous finding of a case of cardiac complication following a third shot of COVID-19 mRNA vaccine. As this case was enrolled in a cohort study, pre-vaccination and pre-symptomatic blood samples were available for genomic and multiplex cytokine analyses., Findings: These analyses revealed the presence of subclinical chronic inflammation, with an elevated expression of RNASE2 at pre-booster baseline as a possible trigger of an acute-on-chronic inflammation that resulted in the cardiac complication. RNASE2 encodes for the ribonuclease RNase2, which cleaves RNA at the 3' side of uridine, which may thus remove the only Toll-like receptor (TLR)-avoidance safety feature of current mRNA vaccines., Conclusions: These pre-booster and pre-symptomatic gene and cytokine expression data provide unique insights into the possible pathogenesis of vaccine-associated cardiac complication and suggest the incorporation of additional nucleoside modification for an added safety margin., Funding: This work was funded by the NMRC Open Fund-Large Collaborative Grant on Integrated Innovations on Infectious Diseases (OFLCG19May-0034)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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30. BNT162b2 mRNA Vaccine-Induced Immune Response in Oral Fluids and Serum.
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Seneviratne CJ, Balan P, de Alwis R, Udawatte NS, Herath T, Toh JZN, Tin GB, Ooi EE, Hong JLG, and Ying JSX
- Subjects
- Humans, COVID-19 Vaccines, SARS-CoV-2, Immunoglobulin G, Immunity, Antibodies, Viral, BNT162 Vaccine, COVID-19 prevention & control
- Abstract
Objectives: The COVID-19 vaccine is currently being administered worldwide to address the ongoing pandemic. Although these vaccines have proven effective in preventing severe disease, the level of immunity required to prevent respiratory mucosal infection remains less well understood. Therefore, it is desirable to develop a noninvasive screening strategy such as oral fluid to monitor secreted antibodies longitudinally as potential surrogates of mucosal immunity., Methods: We evaluated the anti-spike protein antibodies in gingival crevicular fluid (GCF) and saliva and compared them to immune responses in the blood of 50 healthy health care workers following 2 doses of intramuscular Pfizer/BioNTech-BNT162b2 vaccine., Results: The antibodies to SARS-CoV-2 spike and subdomain proteins (RBD, S1, S2, and NTD) were significantly higher in serum than oral fluids but showed a greater detection rate and higher median titres in GCF than saliva. For all tested SARS-CoV-2 antigens, IgG in GCF (as opposed to saliva) showed a more significant and stronger correlation with IgG in serum. Serum-neutralising antibodies (Nab) titres also displayed a significant and stronger correlation with anti-spike protein and their subdomains in GCF than saliva. Interestingly, the time post-second dose of vaccine and sex had a similar influence on IgG in serum and GCF. However, interferon (IFN)-γ-producing T-cell responses showed no association with SARS-Cov-2 IgG antibodies in serum, GCF, or saliva and neutralisation antibodies in serum. The correlation matrix of all measured parameters grouped serum and GCF IgG parameters separately from salivary IgG parameters indicating that GCF better represents the humoural response in serum than saliva., Conclusions: Within limitations, we propose that GCF could be a less invasive alternative to serum and more appropriate than saliva to detect antibody responses by current COVID-19 vaccines if the GCF collection procedure could be standardised. Further research is needed to investigate the suitability of GCF for community immune surveillance for vaccines., Competing Interests: Conflict of interest None disclosed., (Copyright © 2022. Published by Elsevier Inc.)
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- 2023
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31. Tissue-specific expansion of Zika virus isogenic variants drive disease pathogenesis.
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Chan KWK, Bifani AM, Watanabe S, Choy MM, Ooi EE, and Vasudevan SG
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- Male, Chlorocebus aethiops, Animals, Mice, Vero Cells, DNA, Complementary genetics, DNA, Complementary metabolism, Virus Replication, RNA, Viral genetics, RNA, Viral metabolism, Zika Virus genetics, Zika Virus Infection
- Abstract
Background: The Asian lineage Zika virus (ZIKV) emerged as a public health emergency in 2016 causing severe neurological pathologies with no apparent historical correlate to the mild, disease-causing innocuous member of the mosquito-borne flavivirus genus that was discovered in Africa in 1947. Replication error rate of RNA viruses combined with viral protein/RNA structural plasticity can lead to evolution of virus-induced pathogenicity that is critical to identify and validate., Methods: Infection studies in cells and A129 interferon alpha/beta receptor deficient mice with ZIKV French Polynesian H/PF/2013 clinical isolate, plaque-purified isogenic clone derivatives as well as infectious cDNA clone derived wild-type and site-specific mutant viruses, were employed together with Next-Generation Sequencing (NGS) to pin-point the contributions of specific viral variants in neurovirulence recapitulated in our ZIKV mouse model., Findings: NGS analysis of the low-passage inoculum virus as well as mouse serum, brain and testis derived virus, revealed specific enrichment in the mouse brain that were not found in the other tissues. Specifically, non-structural (NS) protein 2A variant at position 117 along with changes in NS1 and NS4B were uniquely associated with the mouse brain isolate. Mutational analysis of these variants in cDNA infectious clones identified the NS2A A117V as the lethal pathogenic determinant with potential epistatic contribution of NS1 and NS4B variants in ZIKV brain penetrance., Interpretation: Our findings confirm that viral subpopulations drive ZIKV neuropathogenicity and identify specific sequence variants that expand in the mouse brain that associates with this phenotype which can serve as predictors of severe epidemics., Funding: Duke-NUS Khoo Post-doctoral Fellowship Award 2020 (KWKC) and National Medical Research Council of Singapore grants MOH-000524 (OFIRG) (SW) and MOH-OFIRG20nov-0002 (SGV)., Competing Interests: Declaration of interests The authors declared no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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32. Proceedings of the 5th Asia Dengue Summit.
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Srisawat N, Gubler DJ, Pangestu T, Thisyakorn U, Ismail Z, Goh D, Capeding MR, Bravo L, Yoksan S, Tantawichien T, Hadinegoro SR, Rafiq K, Picot VS, and Ooi EE
- Abstract
The 5th Asia Dengue Summit, themed "Roll Back Dengue", was held in Singapore from 13 to 15 June 2022. The summit was co-convened by Asia Dengue Voice and Action (ADVA), Global Dengue and Aedes transmitted Diseases Consortium (GDAC), Southeast Asian Ministers of Education Tropical Medicine and Public Health Network (SEAMEO TROPMED), and the Fondation Mérieux (FMx). Dengue experts from academia and research and representatives from the Ministries of Health, Regional and Global World Health Organization (WHO), and International Vaccine Institute (IVI) participated in the three-day summit. With more than 270 speakers and delegates from over 14 countries, 12 symposiums, and 3 full days, the 5th ADS highlighted the growing threat of dengue, shared innovations and strategies for successful dengue control, and emphasized the need for multi-sectoral collaboration to control dengue.
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- 2023
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33. An experimental medicine decipher of a minimum correlate of cellular immunity: Study protocol for a double-blind randomized controlled trial.
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Kalimuddin S, Chan YFZ, Sessions OM, Chan KR, Ong EZ, Low JG, Bertoletti A, and Ooi EE
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- Adult, Humans, Antibodies, Viral, Immunity, Cellular, Antigens, Viral, Randomized Controlled Trials as Topic, Encephalitis, Japanese, Japanese Encephalitis Vaccines, Biomedical Research
- Abstract
Vaccination induces an adaptive immune response that protects against infectious diseases. A defined magnitude of adaptive immune response that correlates with protection from the disease of interest, or correlates of protection (CoP), is useful for guiding vaccine development. Despite mounting evidence for the protective role of cellular immunity against viral diseases, studies on CoP have almost exclusively focused on humoral immune responses. Moreover, although studies have measured cellular immunity following vaccination, no study has defined if a "threshold" of T cells, both in frequency and functionality, is needed to reduce infection burden. We will thus conduct a double-blind, randomized clinical trial in 56 healthy adult volunteers, using the licensed live-attenuated yellow fever (YF17D) and chimeric Japanese encephalitis-YF17D (JE-YF17D) vaccines. These vaccines share the entire non-structural and capsid proteome where the majority of the T cell epitopes reside. The neutralizing antibody epitopes, in contrast, are found on the structural proteins which are not shared between the two vaccines and are thus distinct from one another. Study participants will receive JE-YF17D vaccination followed by YF17D challenge, or YF17D vaccination followed by JE-YF17D challenge. A separate cohort of 14 healthy adults will receive the inactivated Japanese Encephalitis virus (JEV) vaccine followed by YF17D challenge that controls for the effect of cross-reactive flaviviral antibodies. We hypothesize that a strong T cell response induced by YF17D vaccination will reduce JE-YF17D RNAemia upon challenge, as compared to JE-YF17D vaccination followed by YF17D challenge. The expected gradient of YF17D-specific T cell abundance and functionality would also allow us to gain insight into a T cell threshold for controlling acute viral infections. The knowledge gleaned from this study could guide the assessment of cellular immunity and vaccine development., Clinical Trial Registration: Clinicaltrials.gov, NCT05568953., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kalimuddin, Chan, Sessions, Chan, Ong, Low, Bertoletti and Ooi.)
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- 2023
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34. Early peripheral blood MCEMP1 and HLA-DRA expression predicts COVID-19 prognosis.
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Chan KR, Koh CWT, Ng DHL, Qin S, Ooi JSG, Ong EZ, Zhang SLX, Sam H, Kalimuddin S, Low JGH, and Ooi EE
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- Humans, Aged, HLA-DR alpha-Chains genetics, SARS-CoV-2, Leukocytes, Mononuclear, Prognosis, COVID-19
- Abstract
Background: Mass vaccination has dramatically reduced the incidence of severe COVID-19, with most cases now presenting as self-limiting upper respiratory tract infections. However, those with co-morbidities, the elderly and immunocompromised, as well as the unvaccinated, remain disproportionately vulnerable to severe COVID-19 and its sequelae. Furthermore, as the effectiveness of vaccination wanes with time, immune escape SARS-CoV-2 variants could emerge to cause severe COVID-19. Reliable prognostic biomarkers for severe disease could be used as early indicator of re-emergence of severe COVID-19 as well as for triaging of patients for antiviral therapy., Methods: We performed a systematic review and re-analysis of 7 publicly available datasets, analysing a total of 140 severe and 181 mild COVID-19 patients, to determine the most consistent differentially regulated genes in peripheral blood of severe COVID-19 patients. In addition, we included an independent cohort where blood transcriptomics of COVID-19 patients were prospectively and longitudinally monitored previously, to track the time in which these gene expression changes occur before nadir of respiratory function. Single cell RNA-sequencing of peripheral blood mononuclear cells from publicly available datasets was then used to determine the immune cell subsets involved., Findings: The most consistent differentially regulated genes in peripheral blood of severe COVID-19 patients were MCEMP1, HLA-DRA and ETS1 across the 7 transcriptomics datasets. Moreover, we found significantly heightened MCEMP1 and reduced HLA-DRA expression as early as four days before the nadir of respiratory function, and the differential expression of MCEMP1 and HLA-DRA occurred predominantly in CD14+ cells. The online platform which we developed is publicly available at https://kuanrongchan-covid19-severity-app-t7l38g.streamlitapp.com/, for users to query gene expression differences between severe and mild COVID-19 patients in these datasets., Interpretation: Elevated MCEMP1 and reduced HLA-DRA gene expression in CD14+ cells during the early phase of disease are prognostic of severe COVID-19., Funding: K.R.C is funded by the National Medical Research Council (NMRC) of Singapore under the Open Fund Individual Research Grant (MOH-000610). E.E.O. is funded by the NMRC Senior Clinician-Scientist Award (MOH-000135-00). J.G.H.L. is funded by the NMRC under the Clinician-Scientist Award (NMRC/CSAINV/013/2016-01). S.K. is funded by the NMRC under the Transition Award. This study was sponsored in part by a generous gift from The Hour Glass., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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35. Durability of Vaccine-Induced and Natural Immunity Against COVID-19: A Narrative Review.
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Pooley N, Abdool Karim SS, Combadière B, Ooi EE, Harris RC, El Guerche Seblain C, Kisomi M, and Shaikh N
- Abstract
Vaccines developed against SARS-CoV-2 have proven to be highly effective in preventing symptomatic infection. Similarly, prior infection with SARS-CoV-2 has been shown to provide substantial protection against reinfection. However, it has become apparent that the protection provided to an individual after either vaccination or infection wanes over time. Waning protection is driven by both waning immunity over time since vaccination or initial infection, and the evolution of new variants of SARS-CoV-2. Both antibody and T/B-cells levels have been investigated as potential correlates of protection post-vaccination or post-infection. The activity of antibodies and T/B-cells provide some potential insight into the underlying causes of waning protection. This review seeks to summarise what is currently known about the waning of protection provided by both vaccination and/or prior infection, as well as the current information on the respective antibody and T/B-cell responses., (© 2023. The Author(s).)
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- 2023
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36. Correction to: Amplified parallel antigen rapid test for point-of-care salivary detection of SARS-CoV-2 with improved sensitivity.
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Tng DJH, Yin BCY, Cao J, Ko KKK, Goh KCM, Chua DXW, Zhang Y, Chua MLK, Low JGH, Ooi EE, and Soo KC
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- 2023
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37. A phase I/II randomized, double-blinded, placebo-controlled trial of a self-amplifying Covid-19 mRNA vaccine.
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Low JG, de Alwis R, Chen S, Kalimuddin S, Leong YS, Mah TKL, Yuen N, Tan HC, Zhang SL, Sim JXY, Chan YFZ, Syenina A, Yee JX, Ong EZ, Sekulovich R, Sullivan BB, Lindert K, Sullivan SM, Chivukula P, Hughes SG, and Ooi EE
- Abstract
Coronavirus disease-19 (Covid-19) pandemic have demonstrated the importantance of vaccines in disease prevention. Self-amplifying mRNA vaccines could be another option for disease prevention if demonstrated to be safe and immunogenic. Phase 1 of this randomized, double-blinded, placebo-controlled trial (N = 42) assessed the safety, tolerability, and immunogenicity in healthy young and older adults of ascending levels of one-dose ARCT-021, a self-amplifying mRNA vaccine against Covid-19. Phase 2 (N = 64) tested two-doses of ARCT-021 given 28 days apart. During phase 1, ARCT-021 was well tolerated up to one 7.5 μg dose and two 5.0 μg doses. Local solicited AEs, namely injection-site pain and tenderness were more common in ARCT-021vaccinated, while systemic solicited AEs, mainly fatigue, headache and myalgia were reported in 62.8% and 46.4% of ARCT-021 and placebo recipients, respectively. Seroconversion rate for anti-S IgG was 100% in all cohorts, except for the 1 μg one-dose in younger adults and the 7.5 μg one-dose in older adults. Anti-S IgG and neutralizing antibody titers showed a general increase with increasing dose, and overlapped with titers in Covid-19 convalescent patients. T-cell responses were also observed in response to stimulation with S-protein peptides. Taken collectively, ARCT-021 is immunogenic and has favorable safety profile for further development., (© 2022. The Author(s).)
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- 2022
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38. A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization.
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Singh T, Hwang KK, Miller AS, Jones RL, Lopez CA, Dulson SJ, Giuberti C, Gladden MA, Miller I, Webster HS, Eudailey JA, Luo K, Von Holle T, Edwards RJ, Valencia S, Burgomaster KE, Zhang S, Mangold JF, Tu JJ, Dennis M, Alam SM, Premkumar L, Dietze R, Pierson TC, Ooi EE, Lazear HM, Kuhn RJ, Permar SR, and Bonsignori M
- Subjects
- Animals, Female, Mice, Antibodies, Neutralizing, Antibodies, Viral, Epitopes, Neutralization Tests, Pregnancy immunology, Zika Virus, Zika Virus Infection immunology, Immunoglobulin M immunology, Immunoglobulin M isolation & purification
- Abstract
Congenital Zika virus (ZIKV) infection results in neurodevelopmental deficits in up to 14% of infants born to ZIKV-infected mothers. Neutralizing antibodies are a critical component of protective immunity. Here, we demonstrate that plasma IgM contributes to ZIKV immunity in pregnancy, mediating neutralization up to 3 months post-symptoms. From a ZIKV-infected pregnant woman, we isolated a pentameric ZIKV-specific IgM (DH1017.IgM) that exhibited ultrapotent ZIKV neutralization dependent on the IgM isotype. DH1017.IgM targets an envelope dimer epitope within domain II. The epitope arrangement on the virion is compatible with concurrent engagement of all ten antigen-binding sites of DH1017.IgM, a solution not available to IgG. DH1017.IgM protected mice against viremia upon lethal ZIKV challenge more efficiently than when expressed as an IgG. Our findings identify a role for antibodies of the IgM isotype in protection against ZIKV and posit DH1017.IgM as a safe and effective candidate immunotherapeutic, particularly during pregnancy., Competing Interests: Declaration of interests M.B., S.R.P., T.S., and K.-K.H. have filed a patent application directed to antibodies that are related to this work. S.R.P. serves as a consultant to Moderna, Merck, Pfizer, GSK, Hoopika, and Dynavax CMV vaccine programs and leads a sponsored research program with Moderna and Merck., (Published by Elsevier Inc.)
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- 2022
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39. A fast-growing dengue virus mutant reveals a dual role of STING in response to infection.
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Ng WC, Kwek SS, Sun B, Yousefi M, Ong EZ, Tan HC, Puschnik AS, Chan KR, Ooi YS, and Ooi EE
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- Immune Evasion, Virus Replication, Signal Transduction, Dengue Virus, Interferon Type I genetics
- Abstract
The four dengue viruses (DENVs) have evolved multiple mechanisms to ensure its survival. Among these mechanisms is the ability to regulate its replication rate, which may contribute to avoiding premature immune activation that limit infection dissemination: DENVs associated with dengue epidemics have shown slower replication rate than pre-epidemic strains. Correspondingly, wild-type DENVs replicate more slowly than their clinically attenuated derivatives. To understand how DENVs 'make haste slowly', we generated and screened for DENV2 mutants with accelerated replication that also induced high type-I interferon (IFN) expression in infected cells. We chanced upon a single NS2B-I114T amino acid substitution, in an otherwise highly conserved amino acid residue. Accelerated DENV2 replication damaged host DNA as mutant infection was dependent on host DNA damage repair factors, namely RAD21, EID3 and NEK5. DNA damage induced cGAS/STING signalling and activated early type-I IFN response that inhibited infection dissemination. Unexpectedly, STING activation also supported mutant DENV replication in infected cells through STING-induced autophagy. Our findings thus show that DENV NS2B has multi-faceted role in controlling DENV replication rate and immune evasion and suggest that the dual role of STING in supporting virus replication within infected cells but inhibiting infection dissemination could be particularly advantageous for live attenuated vaccine development.
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- 2022
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40. Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine.
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Ong EZ, Yee JX, Ooi JSG, Syenina A, de Alwis R, Chen S, Sim JXY, Kalimuddin S, Leong YS, Chan YFZ, Sekulovich R, Sullivan BM, Lindert K, Sullivan SB, Chivukula P, Hughes SG, Low JG, Ooi EE, and Chan KR
- Abstract
Remarkable potency has been demonstrated for mRNA vaccines in reducing the global burden of the ongoing COVID-19 pandemic. An alternative form of the mRNA vaccine is the self-amplifying mRNA (sa-mRNA) vaccine, which encodes an alphavirus replicase that self-amplifies the full-length mRNA and SARS-CoV-2 spike (S) transgene. However, early-phase clinical trials of sa-mRNA COVID-19 vaccine candidates have questioned the potential of this platform to develop potent vaccines. We examined the immune gene response to a candidate sa-mRNA vaccine against COVID-19, ARCT-021, and compared our findings to the host response to other forms of vaccines. In blood samples from healthy volunteers that participated in a phase I/II clinical trial, greater induction of transcripts involved in Toll-like receptor (TLR) signalling, antigen presentation and complement activation at 1 day post-vaccination was associated with higher anti-S antibody titers. Conversely, transcripts involved in T-cell maturation at day 7 post-vaccination informed the magnitude of eventual S-specific T-cell responses. The transcriptomic signature for ARCT-021 vaccination strongly correlated with live viral vector vaccines, adjuvanted vaccines and BNT162b2 1 day post-vaccination. Moreover, the ARCT-021 signature correlated with day 7 YF17D live-attenuated vaccine transcriptomic responses. Altogether, our findings show that sa-mRNA vaccination induces innate immune responses that are associated with the development of adaptive immunity from other forms of vaccines, supporting further development of this vaccine platform for clinical application., (© 2022. The Author(s).)
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- 2022
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41. Externalities modulate the effectiveness of the Wolbachia release programme.
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Ooi EE and Wilder-Smith A
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- Animals, Humans, Wolbachia, Aedes, Dengue
- Abstract
Competing Interests: We declare no competing interests. AW-S serves as a Consultant to WHO. The views and opinions expressed here are those of the author and not necessarily of WHO.
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- 2022
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42. Modulate Cellular Stress in the Immune Cells to Reduce Rate of Symptomatic Viral Infection
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Duke-NUS Graduate Medical School
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- 2024
43. RNA Viruses, Pandemics and Anticipatory Preparedness.
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Garcia-Blanco MA, Ooi EE, and Sessions OM
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- Animals, Humans, Pandemics prevention & control, Disease Outbreaks prevention & control, Antiviral Agents therapeutic use, RNA Viruses, Influenza, Human epidemiology, Influenza, Human prevention & control, Influenza, Human drug therapy
- Abstract
RNA viruses are likely to cause future pandemics and therefore we must create and organize a deep knowledge of these viruses to prevent and manage this risk. Assuming prevention will fail, at least once, we must be prepared to manage a future pandemic using all resources available. We emphasize the importance of having safe vaccine candidates and safe broad-spectrum antivirals ready for rapid clinical translation. Additionally, we must have similar tools to be ready for outbreaks of RNA viruses among animals and plants. Finally, similar coordination should be accomplished for other pathogens with pandemic potential.
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- 2022
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44. Identification of Aedes aegypti salivary gland proteins interacting with human immune receptor proteins.
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Gavor E, Choong YK, Liu Y, Pompon J, Ooi EE, Mok YK, Liu H, Kini RM, and Sivaraman J
- Subjects
- Allergens, Animals, Apyrase, Humans, Intercellular Adhesion Molecule-3 metabolism, Mosquito Vectors, Recombinant Proteins metabolism, Toll-Like Receptor 4 metabolism, Aedes, Salivary Proteins and Peptides metabolism
- Abstract
Mosquito saliva proteins modulate the human immune and hemostatic systems and control mosquito-borne pathogenic infections. One mechanism through which mosquito proteins may influence host immunity and hemostasis is their interactions with key human receptor proteins that may act as receptors for or coordinate attacks against invading pathogens. Here, using pull-down assays and proteomics-based mass spectrometry, we identified 11 Ae. aegypti salivary gland proteins (SGPs) (e.g., apyrase, Ae. aegypti venom allergen-1 [AaVA-1], neutrophil stimulating protein 1 [NeSt1], and D7 proteins), that interact with one or more of five human receptor proteins (cluster of differentiation 4 [CD4], CD14, CD86, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin [DC-SIGN], and Toll-like receptor 4 [TLR4]). We focused on CD4- and DC-SIGN-interacting proteins and confirmed that CD4 directly interacts with AaVA-1, D7, and NeST1 recombinant proteins and that AaVA-1 showed a moderate interaction with DC-SIGN using ELISA. Bacteria responsive protein 1 (AgBR1), an Ae. aegypti saliva protein reported to enhance ZIKV infection in humans but that was not identified in our pull-down assay moderately interacts with CD4 in the ELISA assay. Functionally, we showed that AaVA-1 and NeST1 proteins promoted activation of CD4+ T cells. We propose the possible impact of these interactions and effects on mosquito-borne viral infections such as dengue, Zika, and chikungunya viruses. Overall, this study provides key insight into the vector-host (protein-protein) interaction network and suggests roles for these interactions in mosquito-borne viral infections., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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45. Monitoring human arboviral diseases through wastewater surveillance: Challenges, progress and future opportunities.
- Author
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Lee WL, Gu X, Armas F, Leifels M, Wu F, Chandra F, Chua FJD, Syenina A, Chen H, Cheng D, Ooi EE, Wuertz S, Alm EJ, and Thompson J
- Subjects
- Humans, Sewage, Wastewater, Wastewater-Based Epidemiological Monitoring, Arbovirus Infections diagnosis, Arbovirus Infections epidemiology, Arboviruses, COVID-19, Zika Virus, Zika Virus Infection diagnosis, Zika Virus Infection epidemiology
- Abstract
Arboviral diseases are caused by a group of viruses spread by the bite of infected arthropods. Amongst these, dengue, Zika, west nile fever and yellow fever cause the greatest economic and social impact. Arboviral epidemics have increased in frequency, magnitude and geographical extent over the past decades and are expected to continue increasing with climate change and expanding urbanisation. Arboviral prevalence is largely underestimated, as most infections are asymptomatic, nevertheless existing surveillance systems are based on passive reporting of loosely defined clinical syndromes with infrequent laboratory confirmation. Wastewater-based surveillance (WBS), which has been demonstrated to be useful for monitoring diseases with significant asymptomatic populations including COVID19 and polio, could be a useful complement to arboviral surveillance. We review the current state of knowledge and identify key factors that affect the feasibility of monitoring arboviral diseases by WBS to include viral shedding loads by infected persons, the persistence of shed arboviruses and the efficiency of their recovery from sewage. We provide a simple model on the volume of wastewater that needs to be processed for detection of arboviruses, in face of lower arboviral shedding rates. In all, this review serves to reflect on the key challenges that need to be addressed and overcome for successful implementation of arboviral WBS., Competing Interests: Declaration of Competing Interest E.J.A. is advisor to Biobot Analytics, Inc. and holds shares in the company., (Copyright © 2022. Published by Elsevier Ltd.)
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- 2022
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46. Chronic sequelae complicate convalescence from both dengue and acute viral respiratory illness.
- Author
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Kalimuddin S, Teh YE, Wee LE, Paintal S, Sasisekharan R, Low JG, Sheth SK, and Ooi EE
- Subjects
- Convalescence, Disease Progression, Humans, Male, Pandemics, Post-Acute COVID-19 Syndrome, COVID-19 complications, Dengue complications, Dengue epidemiology, Respiratory Tract Infections complications, Respiratory Tract Infections epidemiology
- Abstract
Long Covid has raised awareness of the potentially disabling chronic sequelae that afflicts patients after acute viral infection. Similar syndromes of post-infectious sequelae have also been observed after other viral infections such as dengue, but their true prevalence and functional impact remain poorly defined. We prospectively enrolled 209 patients with acute dengue (n = 48; one with severe dengue) and other acute viral respiratory infections (ARI) (n = 161), and followed them up for chronic sequelae up to one year post-enrolment, prior to the onset of the Covid-19 pandemic. Baseline demographics and co-morbidities were balanced between both groups except for gender, with more males in the dengue cohort (63% vs 29%, p<0.001). Except for the first visit, data on symptoms were collected remotely using a purpose-built mobile phone application. Mental health outcomes were evaluated using the validated SF-12v2 Health Survey. Almost all patients (95.8% of dengue and 94.4% of ARI patients) experienced at least one symptom of fatigue, somnolence, headache, concentration impairment or memory impairment within the first week of enrolment. Amongst patients with at least 3-months of follow-up, 18.0% in the dengue cohort and 14.6% in the ARI cohort experienced persistent symptoms. The median month-3 SF-12v2 Mental Component Summary Score was lower in patients who remained symptomatic at 3 months and beyond, compared to those whose symptoms fully resolved (47.7 vs. 56.0, p<0.001), indicating that patients who self-reported persistence of symptoms also experienced functionally worse mental health. No statistically significant difference in age, gender distribution or hospitalisation status was observed between those with and without chronic sequelae. Our findings reveal an under-appreciated burden of post-infection chronic sequelae in dengue and ARI patients. They call for studies to define the pathophysiology of this condition, and determine the efficacy of both vaccines as well as antiviral drugs in preventing such sequelae., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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47. TMEM41B and VMP1 modulate cellular lipid and energy metabolism for facilitating dengue virus infection.
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Yousefi M, Lee WS, Yan B, Cui L, Yong CL, Yap X, Tay KSL, Qiao W, Tan D, Nurazmi NI, Linster M, Smith GJD, Lee YH, Carette JE, Ooi EE, Chan KR, and Ooi YS
- Subjects
- Energy Metabolism, Humans, Lipids, Membrane Proteins genetics, Virus Replication, Coronavirus, Coronavirus Infections, Dengue
- Abstract
Transmembrane Protein 41B (TMEM41B) and Vacuole Membrane Protein 1 (VMP1) are two ER-associated lipid scramblases that play a role in autophagosome formation and cellular lipid metabolism. TMEM41B is also a recently validated host factor required by flaviviruses and coronaviruses. However, the exact underlying mechanism of TMEM41B in promoting viral infections remains an open question. Here, we validated that both TMEM41B and VMP1 are essential host dependency factors for all four serotypes of dengue virus (DENV) and human coronavirus OC43 (HCoV-OC43), but not chikungunya virus (CHIKV). While HCoV-OC43 failed to replicate entirely in both TMEM41B- and VMP1-deficient cells, we detected diminished levels of DENV infections in these cell lines, which were accompanied by upregulation of the innate immune dsRNA sensors, RIG-I and MDA5. Nonetheless, this upregulation did not correspondingly induce the downstream effector TBK1 activation and Interferon-beta expression. Despite low levels of DENV replication, classical DENV replication organelles were undetectable in the infected TMEM41B-deficient cells, suggesting that the upregulation of the dsRNA sensors is likely a consequence of aberrant viral replication rather than a causal factor for reduced DENV infection. Intriguingly, we uncovered that the inhibitory effect of TMEM41B deficiency on DENV replication, but not HCoV-OC43, can be partially reversed using exogenous fatty acid supplements. In contrast, VMP1 deficiency cannot be rescued using the metabolite treatment. In line with the observed phenotypes, we found that both TMEM41B- and VMP1-deficient cells harbor higher levels of compromised mitochondria, especially in VMP1 deficiency which results in severe dysregulations of mitochondrial beta-oxidation. Using a metabolomic profiling approach, we revealed distinctive global dysregulations of the cellular metabolome, particularly lipidome, in TMEM41B- and VMP1-deficient cells. Our findings highlight a central role for TMEM41B and VMP1 in modulating multiple cellular pathways, including lipid mobilization, mitochondrial beta-oxidation, and global metabolic regulations, to facilitate the replication of flaviviruses and coronaviruses., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2022
- Full Text
- View/download PDF
48. Issues of Entering New Market and Ways to Overcome the Issues Company: F&N Holdings Berhad
- Author
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Jun, Ooi Ee, primary, Kee, Daisy Mui Hung, additional, Wen, Tan Xiang, additional, Chen, Koay Xiem, additional, Qi, Ma Jia, additional, and AlDeehani, Faisal, additional
- Published
- 2019
- Full Text
- View/download PDF
49. Adverse effects following anti-COVID-19 vaccination with mRNA-based BNT162b2 are alleviated by altering the route of administration and correlate with baseline enrichment of T and NK cell genes.
- Author
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Syenina A, Gan ES, Toh JZN, de Alwis R, Lin LZ, Tham CYL, Yee JX, Leong YS, Sam H, Cheong C, Teh YE, Wee ILE, Ng DHL, Chan KR, Sim JXY, Kalimuddin S, Ong EZ, Low JG, and Ooi EE
- Subjects
- Animals, BNT162 Vaccine, COVID-19 Vaccines adverse effects, Fatigue etiology, Humans, Killer Cells, Natural, Mice, RNA, Messenger genetics, Vaccination adverse effects, COVID-19 prevention & control
- Abstract
Ensuring high vaccination and even booster vaccination coverage is critical in preventing severe Coronavirus Disease 2019 (COVID-19). Among the various COVID-19 vaccines currently in use, the mRNA vaccines have shown remarkable effectiveness. However, systemic adverse events (AEs), such as postvaccination fatigue, are prevalent following mRNA vaccination, and the underpinnings of which are not understood. Herein, we found that higher baseline expression of genes related to T and NK cell exhaustion and suppression were positively correlated with the development of moderately severe fatigue after Pfizer-BioNTech BNT162b2 vaccination; increased expression of genes associated with T and NK cell exhaustion and suppression reacted to vaccination were associated with greater levels of innate immune activation at 1 day postvaccination. We further found, in a mouse model, that altering the route of vaccination from intramuscular (i.m.) to subcutaneous (s.c.) could lessen the pro-inflammatory response and correspondingly the extent of systemic AEs; the humoral immune response to BNT162b2 vaccination was not compromised. Instead, it is possible that the s.c. route could improve cytotoxic CD8 T-cell responses to BNT162b2 vaccination. Our findings thus provide a glimpse of the molecular basis of postvaccination fatigue from mRNA vaccination and suggest a readily translatable solution to minimize systemic AEs., Competing Interests: The authors have declared no competing interests exists.
- Published
- 2022
- Full Text
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50. As Omicron Takes Hold and Other New Variants Arise, COVID-19 Testing Remains the Universally Agreed Tool to Effect Transition From Pandemic to Endemic State.
- Author
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Miller MB, Ooi EE, Rhoads DD, Kulldorff M, Anderson DE, Lee H, Gupta S, and Mel K
- Subjects
- COVID-19 Testing, Humans, Pandemics, COVID-19 diagnosis, COVID-19 epidemiology, SARS-CoV-2 genetics
- Abstract
The COVID-19 pandemic has caused more than 448 million cases and 6 million deaths worldwide to date. Omicron is now the dominant SARS-CoV-2 variant, making up more than 90% of cases in countries reporting sequencing data. As the pandemic continues into its third year, continued testing is a strategic and necessary tool for transitioning to an endemic state of COVID-19. Here, we address three critical topics pertaining to the transition from pandemic to endemic: defining the endemic state for COVID-19, highlighting the role of SARS-CoV-2 testing as endemicity is approached, and recommending parameters for SARS-CoV-2 testing once endemicity is reached. We argue for an approach that capitalizes on the current public health momentum to increase capacity for PCR-based testing and whole genome sequencing to monitor emerging infectious diseases. Strategic development and utilization of testing, including viral panels in addition to vaccination, can keep SARS-CoV-2 in a manageable endemic state and build a framework of preparedness for the next pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Miller, Ooi, Rhoads, Kulldorff, Anderson, Lee, Gupta and Mel.)
- Published
- 2022
- Full Text
- View/download PDF
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