ORCID Profile
0000-0002-0520-1544
Current Organisations
University of Nottingham
,
National University of Singapore
,
Duke-NUS Medical School
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Publications
A Simple and Powerful Method for the Estimation of Intervention Effects on Serological Endpoints Using Paired Interval-Censored Data
Publisher: Informa UK Limited
Date: 02-01-2015
DOI: 10.1080/10543406.2014.919936
Abstract: Clinical trials often use a binary "fold increase" endpoint defined according to the ratio of interval-censored measurement at end-of-study to that at baseline. We propose a simple yet principled analytic approach based on the linear mixed-effects model for interval-censored data for the analysis of such paired measurements. Having estimated the model parameters, the risk ratio can be estimated by explicit composite estimand and the variance is estimated using the delta method. The estimation can be implemented using the existing procedures in popular statistical software. We use antibody data from the Chloroquine for Influenza Prevention Trial for illustration.
A highly divergent Encephalomyocarditis virus isolated from nonhuman primates in Singapore
Publisher: Springer Science and Business Media LLC
Date: 02-08-2013
Abstract: In 2001 and 2002, fatal myocarditis resulted in the sudden deaths of four, two adult and two juvenile, orang utans out of a cohort of 26 in the Singapore Zoological Gardens. Of the four orang utans that underwent post-mortem examination, virus isolation was performed from the tissue homogenates of the heart and lung obtained from the two juvenile orang utans in Vero cell cultures. The tissue culture fluid was examined using electron microscopy. Reverse transcription and polymerase chain reaction with Encephalomyocarditis virus (EMCV)-specific primers targeting the gene regions of VP3/VP1 and 3D polymerase (3Dpol) confirmed the virus genus and species. The two EMCV isolates were sequenced and phylogenetic analyses of the virus genes performed. Serological testing on other animal species in the Singapore Zoological Gardens was also conducted. Electron microscopy of the two EMCV isolates, designated Sing-M100-02 and Sing-M105-02, revealed spherical viral particles of about 20 to 30 nm, consistent with the size and morphology of members belonging to the family Picornaviridae . In addition, infected-Vero cells showed positive immunoflorescence staining with antiserum to EMCV. Sequencing of the viral genome showed that the two EMCV isolates were 99.9% identical at the nucleotide level, indicating a similar source of origin. When compared with existing EMCV sequences in the VP1 and 3Dpol gene regions, the nucleotide ergence were at a maximum of 38.8% and 23.6% respectively, while the amino acid ergence were at a maximum of 33.9% and 11.3% respectively. Phylogenetic analyses of VP1 and 3Dpol genes further grouped the Sing-M100-02 and Sing-M105-02 isolates to themselves, away from existing EMCV lineages. This strongly suggested that Sing-M100-02 and Sing-M105-02 isolates are highly ergent variants of EMCV. Apart from the two deceased orang utans, a serological survey conducted among other zoo animals showed that a number of other animal species had neutralizing antibodies to Sing-M105-02 isolate, indicating that the EMCV variant has a relatively wide host range. The etiological agent responsible for the fatal myocarditis cases among two of the four orang utans in the Singapore Zoological Gardens was a highly ergent variant of EMCV. This is the first report of an EMCV infection in Singapore and South East Asia.
Association Between Increased Vascular Nitric Oxide Bioavailability and Progression to Dengue Hemorrhagic Fever in Adults
Publisher: Oxford University Press (OUP)
Date: 02-03-2015
Abstract: In a prospective longitudinal adult study, vascular nitric oxide bioavailability measured as reactive hyperemia index was significantly higher at enrollment in patients who developed dengue hemorrhagic fever (DHF) (n = 11), compared with the non-DHF group (n = 63) and those with other febrile illnesses (n = 25) (P = .01). After adjustment for age, fever day, and body mass index, enrollment reactive hyperemia index was associated with a 4-fold increased risk for DHF, and predicted DHF with an area under the receiver operating curve of 0.86. Increased vascular nitric oxide in dengue is associated with increased vascular permeability and impaired homeostasis and may have utility as a predictor of DHF.
Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection
Publisher: Springer Science and Business Media LLC
Date: 30-10-2013
Update on Dengue: Epidemiology, Virus Evolution, Antiviral Drugs, and Vaccine Development
Publisher: Springer Science and Business Media LLC
Date: 30-03-2010
DOI: 10.1007/S11908-010-0102-7
Abstract: Dengue virus is the most widespread geographically of the arboviruses and a major public health threat in the tropics and subtropics. Scientific advances in recent years have provided new insights about the pathogenesis of more severe disease and novel approaches into the development of antiviral compounds and dengue vaccines. Phylogenetic studies show an association between specific subtypes (within serotypes) and severity of dengue. The lack of association between maternal antibodies and development of severe dengue in infants in a recent study has called for the rethinking or refinement of the current antibody-dependent enhancement theory of dengue hemorrhagic syndrome in infancy. Such studies should stimulate new directions of research into mechanisms responsible for the development of severe dengue. The life cycle of dengue virus readily shows that virus entry and replication can be targeted by small molecules. Advances in a mouse model (AG 129 mice) have made it easier to test such antiviral compounds. The efforts to find specific dengue inhibitors are intensifying and the tools to evaluate the efficacy of new drugs are now in place for rapid translation into trials in humans. Furthermore, several dengue vaccine candidates are in development, of which the chimeric dengue/yellow fever vaccine has now entered phase 3 trials. Until the availability of a licensed vaccine, disease surveillance and vector population control remain the mainstay of dengue prevention.
Serological response to trivalent inactivated influenza vaccine in HIV-infected adults in Singapore
Publisher: Informa UK Limited
Date: 17-02-2017
Prophylactic platelet transfusion plus supportive care versus supportive care alone in adults with dengue and thrombocytopenia: a multicentre, open-label, randomised, superiority trial
Publisher: Elsevier BV
Date: 04-2017
Decision Tree Algorithms Predict the Diagnosis and Outcome of Dengue Fever in the Early Phase of Illness
Publisher: Public Library of Science (PLoS)
Date: 12-03-2008
Profiles of Antibody Responses against Severe AcuteRespiratory Syndrome Coronavirus Recombinant Proteins andTheir Potential Use as DiagnosticMarkers
Publisher: American Society for Microbiology
Date: 03-2004
DOI: 10.1128/CDLI.11.2.362-371.2004
Abstract: A new coronavirus (severe acute respiratory syndrome coronavirus [SARS-CoV]) has been identified to be the etiological agent of severe acute respiratory syndrome. Given the highly contagious and acute nature of the disease, there is an urgent need for the development of diagnostic assays that can detect SARS-CoV infection. For determination of which of the viral proteins encoded by the SARS-CoV genome may be exploited as diagnostic antigens for serological assays, the viral proteins were expressed in idually in mammalian and/or bacterial cells and tested for reactivity with sera from SARS-CoV-infected patients by Western blot analysis. A total of 81 sera, including 67 from convalescent patients and seven pairs from two time points of infection, were analyzed, and all showed immunoreactivity towards the nucleocapsid protein (N). Sera from some of the patients also showed immunoreactivity to U274 (59 of 81 [73%]), a protein that is unique to SARS-CoV. In addition, all of the convalescent-phase sera showed immunoreactivity to the spike (S) protein when analyzed by an immunofluorescence method utilizing mammalian cells stably expressing S. However, s les from the acute phase (2 to 9 days after the onset of illness) did not react with S, suggesting that antibodies to N may appear earlier than antibodies to S. Alternatively, this could be due to the difference in the sensitivities of the two methods. The immunoreactivities to these recombinant viral proteins are highly specific, as sera from 100 healthy donors did not react with any of them. These results suggest that recombinant N, S, and U274 proteins may be used as antigens for the development of serological assays for SARS-CoV.
Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients
Publisher: Public Library of Science (PLoS)
Date: 10-08-2016
A T164S mutation in the dengue virus NS1 protein is associated with greater disease severity in mice
Publisher: American Association for the Advancement of Science (AAAS)
Date: 26-06-2019
DOI: 10.1126/SCITRANSLMED.AAT7726
Abstract: The T164S mutation in the NS1 protein of dengue virus increases disease severity in mice through complement activation.
Induction of Human T-cell and Cytokine Responses Following Vaccination with a Novel Influenza Vaccine
Publisher: Springer Science and Business Media LLC
Date: 20-12-2018
DOI: 10.1038/S41598-018-36703-7
Abstract: Cell mediated immunity plays a vital role in defense against influenza infection in humans. Less is known about the role of vaccine-induced cell mediated immunity and the cytokine responses elicited. We measured CD4 + and CD8 + T-cell reactivity in human subjects following vaccination with licensed trivalent influenza vaccine and a novel virus-like particle based vaccine. We detected influenza-specific CD4 + T-cell responses following vaccination with the licensed trivalent influenza vaccine and found that these correlated with antibody measurements. Administration of the novel virus-like particle based vaccine elicited influenza-specific CD4 + and CD8 + T-cell responses and the induction of the cytokines IFN-γ, IL-17A, IL17F, IL-5, IL-13, IL-9, IL-10 and IL-21. Pre-existing cytokine responses influenced the profile of the cytokine response elicited by vaccination. In a subset of in iduals the VLP vaccine changed pre-vaccination production of type 2 cytokines such as IL-5 and IL-13 to a post-vaccination type 1 cytokine signature characterized by IFN-γ. A transcriptional signature to vaccination was found to correlate with antibody titer, IFN-γ production by T-cells and expression of a putative RNA helicase, DDX17, on the surface of immune cells.
The Structural Basis for Serotype-Specific Neutralization of Dengue Virus by a Human Antibody
Publisher: American Association for the Advancement of Science (AAAS)
Date: 20-06-2012
DOI: 10.1126/SCITRANSLMED.3003888
Abstract: The mechanism of action of a serotype-specific natural human antibody against dengue virus has been identified.
A Human PrM Antibody That Recognizes a Novel Cryptic Epitope on Dengue E Glycoprotein
Publisher: Public Library of Science (PLoS)
Date: 03-04-2012
Immune correlates of protection for dengue: State of the art and research agenda
Publisher: Elsevier BV
Date: 08-2017
Economic Impact of Dengue Illness and the Cost-Effectiveness of Future Vaccination Programs in Singapore
Publisher: Public Library of Science (PLoS)
Date: 20-12-2011
Higher Risk of Infection with Dengue at the Weekend among Male Singaporeans
Publisher: American Society of Tropical Medicine and Hygiene
Date: 05-12-2012
The C-terminal 18 amino acid region of Dengue virus NS5 regulates its subcellular localization and contains a conserved arginine residue essential for infectious virus production
Publisher: Public Library of Science (PLoS)
Date: 13-09-2016
Positive epistasis between viral polymerase and the 3′ untranslated region of its genome reveals the epidemiologic fitness of dengue virus
Publisher: Proceedings of the National Academy of Sciences
Date: 04-05-2020
Abstract: Dengue affects approximately one-half of the world’s population. While it causes regular and cyclical outbreaks throughout the tropical world, the molecular mechanisms that determine its epidemic potential remain poorly defined. The present work provides insight into the molecular determinants of epidemiologic fitness, which is critical for surveillance to identify dengue virus strains with a potential to cause outbreaks. This will allow for better implementation of control measures to intercept impending outbreaks before many lives are affected.
Activation of the innate immune system provides broad-spectrum protection against influenza A viruses with pandemic potential in mice
Publisher: Elsevier BV
Date: 10-2010
Assessing the epidemiological effect of wolbachia for dengue control
Publisher: Elsevier BV
Date: 07-2015
A Novel Severe Acute Respiratory Syndrome Coronavirus Protein, U274, Is Transported to the Cell Surface and Undergoes Endocytosis
Publisher: American Society for Microbiology
Date: 07-2004
DOI: 10.1128/JVI.78.13.6723-6734.2004
Abstract: The severe acute respiratory syndrome coronavirus (SARS-CoV) genome contains open reading frames (ORFs) that encode for several genes that are homologous to proteins found in all known coronaviruses. These are the replicase gene 1a/1b and the four structural proteins, nucleocapsid (N), spike (S), membrane (M), and envelope (E), and these proteins are expected to be essential for the replication of the virus. In addition, this genome also contains nine other potential ORFs varying in length from 39 to 274 amino acids. The largest among these is the first ORF of the second longest subgenomic RNA, and this protein (termed U274 in the present study) consists of 274 amino acids and contains three putative transmembrane domains. Using antibody specific for the C terminus of U274, we show U274 to be expressed in SARS-CoV-infected Vero E6 cells and, in addition to the full-length protein, two other processed forms were also detected. By indirect immunofluorescence, U274 was localized to the perinuclear region, as well as to the plasma membrane, in both transfected and infected cells. Using an N terminus myc-tagged U274, the topology of U274 and its expression on the cell surface were confirmed. Deletion of a cytoplasmic domain of U274, which contains Yxxφ and diacidic motifs, abolished its transport to the cell surface. In addition, U274 expressed on the cell surface can internalize antibodies from the culture medium into the cells. Coimmunoprecipitation experiments also showed that U274 could interact specifically with the M, E, and S structural proteins, as well as with U122, another protein that is unique to SARS-CoV.
Seroepidemiology of neutralizing antibodies to Japanese encephalitis virus in Singapore: continued transmission despite abolishment of pig farming?
Publisher: Elsevier BV
Date: 11-2004
DOI: 10.1016/J.ACTATROPICA.2004.04.010
Abstract: Japanese encephalitis virus (JEV) transmission in Singapore appeared to have ceased after pig farming in Singapore was phased out from the early 1980s. However, the recent detection of neutralizing antibodies to JEV in a population of wild boars in an offshore island, as well as the notification of two human cases of JE in Singapore in 2001, prompted us to reconsider the presence and hence the public health threat of JEV in Singapore. We report here a serological study of animals, birds and humans for neutralizing antibodies to JEV. The results indicate that JEV may still be actively transmitted in the peripheral part of the Singapore island and that regular serological surveys of farm animals and birds, such as chickens, may be useful to further elucidate the activity of JEV in Singapore.
Characterization of a Unique Group-Specific Protein (U122) of the Severe Acute Respiratory Syndrome Coronavirus
Publisher: American Society for Microbiology
Date: 15-07-2004
DOI: 10.1128/JVI.78.14.7311-7318.2004
Abstract: A novel coronavirus (CoV) has been identified as the etiological agent of severe acute respiratory syndrome (SARS). The SARS-CoV genome encodes the characteristic essential CoV replication and structural proteins. Additionally, the genome contains six group-specific open reading frames (ORFs) larger than 50 amino acids, with no known homologues. As with the group-specific genes of the other CoVs, little is known about the SARS-CoV group-specific genes. SARS-CoV ORF7a encodes a putative unique 122-amino-acid protein, designated U122 in this study. The deduced sequence contains a probable cleaved signal sequence and a C-terminal transmembrane helix, indicating that U122 is likely to be a type I membrane protein. The C-terminal tail also contains a typical endoplasmic reticulum (ER) retrieval motif, KRKTE. U122 was expressed in SARS-CoV-infected Vero E6 cells, as it could be detected by Western blot and immunofluorescence analyses. U122 is localized to the perinuclear region of both SARS-CoV-infected and transfected cells and colocalized with ER and intermediate compartment markers. Mutational analyses showed that both the signal peptide sequence and ER retrieval motif were functional.
Genomic Epidemiology of a Dengue Virus Epidemic in Urban Singapore
Publisher: American Society for Microbiology
Date: 05-2009
DOI: 10.1128/JVI.02445-08
Abstract: Dengue is one of the most important emerging diseases of humans, with no preventative vaccines or antiviral cures available at present. Although one-third of the world's population live at risk of infection, little is known about the pattern and dynamics of dengue virus (DENV) within outbreak situations. By exploiting genomic data from an intensively studied major outbreak, we are able to describe the molecular epidemiology of DENV at a uniquely fine-scaled temporal and spatial resolution. Two DENV serotypes (DENV-1 and DENV-3), and multiple component genotypes, spread concurrently and with similar epidemiological and evolutionary profiles during the initial outbreak phase of a major dengue epidemic that took place in Singapore during 2005. Although DENV-1 and DENV-3 differed in viremia and clinical outcome, there was no evidence for adaptive evolution before, during, or after the outbreak, indicating that ecological or immunological rather than virological factors were the key determinants of epidemic dynamics.
Genetic diversity of respiratory enteroviruses and rhinoviruses in febrile adults, Singapore, 2007‐2013
Publisher: Wiley
Date: 30-09-2019
DOI: 10.1111/IRV.12662
Cross-Reactivity and Anti-viral Function of Dengue Capsid and NS3-Specific Memory T Cells Toward Zika Virus
Publisher: Frontiers Media SA
Date: 10-2018
The combination of Type i IFN, TNF-α, and cell surface receptor engagement with dendritic cells enables nk cells to overcome immune evasion by dengue virus
Publisher: The American Association of Immunologists
Date: 15-11-2014
Abstract: Clinical studies have suggested the importance of the NK cell response against dengue virus (DenV), an arboviral infection that afflicts & million in iduals each year. However, a comprehensive understanding of the NK cell response against dengue-infected cells is lacking. To characterize cell-contact mechanisms and soluble factors that contribute to the antidengue response, primary human NK cells were cocultured with autologous DenV-infected monocyte-derived dendritic cells (DC). NK cells responded by cytokine production and the lysis of target cells. Notably, in the absence of significant monokine production by DenV-infected DC, it was the combination of type I IFNs and TNF-α produced by DenV-infected DC that was important for stimulating the IFN-γ and cytotoxic responses of NK cells. Cell-bound factors enhanced NK cell IFN-γ production. In particular, reduced HLA class I expression was observed on DenV-infected DC, and IFN-γ production was enhanced in licensed/educated NK cell subsets. NK–DC cell contact was also identified as a requirement for a cytotoxic response, and there was evidence for both perforin/granzyme as well as Fas/Fas ligand–dependent pathways of killing by NK cells. In summary, our results have uncovered a previously unappreciated role for the combined effect of type I IFNs, TNF-α, and cell surface receptor–ligand interactions in triggering the antidengue response of primary human NK cells.
Regarding Dengue--How Best to Classify It
Publisher: Oxford University Press (OUP)
Date: 02-04-2012
DOI: 10.1093/CID/CIS328
Implementation strategies for the first licensed dengue vaccine: A meeting report
Publisher: Elsevier BV
Date: 08-2021
DOI: 10.1016/J.VACCINE.2021.06.083
Abstract: Dengue vaccination would enhance the control of dengue, one of the most frequent vector-borne viral diseases globally. CYD-TDV is the first dengue vaccine to be licensed, but global uptake has been h ered due to its use being limited to seropositive persons aged 9 years and above, and the need for a 3-dose schedule. The Partnership for Dengue Control (PDC) organized a meeting with key opinion leaders and stakeholders to deliberate on implementation strategies for the use of CYD-TDV. New data have emerged that support the shortening of the primary schedule from a 3 to 2 dose schedule, extending the age range below 9 to 6 years of age, and expanding the indication from endemic populations to also include travelers to endemic areas. Cost-effectiveness may improve with the modified 2-dose regimen and with multiple testing. Strategies to implement a dengue vaccination program have been developed, in particular school-based strategies. A range of delivery scenarios can then be considered, using various settings for each step of the intervention. However, several challenges remain, including communication about limiting the use of this vaccine to seropositive in iduals only. Affordability will vary from country to country, as will government commitment and community acceptance. Well-tailored communication strategies that target key stakeholders are expected to make up a significant part of any future dengue vaccination program.
The C-terminal 50 Amino Acid Residues of Dengue NS3 Protein Are Important for NS3-NS5 Interaction and Viral Replication
Publisher: Elsevier BV
Date: 2015
Rapid measurement of SARS-CoV-2 spike T cells in whole blood from vaccinated and naturally infected individuals
Publisher: American Society for Clinical Investigation
Date: 30-03-2022
DOI: 10.1172/JCI152379
Topographic Changes in SARS Coronavirus–infected Cells at Late Stages of Infection
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 11-2004
Abstract: Scanning electron and atomic force microscopy was used for the first time to view the maturation of the severe acute respiratory syndrome-associated coronavirus at the cell surface. The surface form of the cells at advanced infection displayed prolific pseudopodia that, in addition to the rest of the plasma membrane, were also active sites of virus release. High magnification of the maturing virus particles showed a rosette appearance with short knoblike spikes under both the scanning electron and atomic force microscopes. The final expulsion step of the maturing virus particles seemed to result in some disruptions to the plasma membrane. The cytoskeletal network along the edge of the infected cells was enhanced and could be involved in transporting and expelling the progeny virus particles. Thickening of the actin filaments at the cell edge provided the bending force to extrude the virus particles.
Leukocyte immunoglobulin-like receptor B1 is critical for antibody-dependent dengue
Publisher: Proceedings of the National Academy of Sciences
Date: 13-01-2014
Abstract: Dengue virus (DENV) infects almost 400 million people annually and some of these infections result in life threatening disease. An incomplete understanding of pathogenesis, particularly on how non- or subneutralizing levels of antibody augments DENV infection of cells expressing Fc-gamma receptors (FcγRs), has h ered vaccine development. Here, we show that, to overcome the activating FcγR-dependent expression of type-I interferon stimulated genes (ISGs), DENV binds and activates the inhibitory receptor, leukocyte immunoglobulin-like receptor-B1 (LILRB1). LILRB1 signals through its immunoreceptor tyrosine-based inhibition motif cytoplasmic tail to inhibit the expression of ISGs required for successful antibody-dependent DENV infection. Inhibition of DENV activation of LILRB1 could hence be a strategy for vaccine or therapeutic design.
Proliferative growth of SARS coronavirus in Vero E6 cells
Publisher: Microbiology Society
Date: 12-2003
Abstract: An isolate of SARS coronavirus (strain 2003VA2774) was obtained from a patient and used to infect Vero E6 cells. The replication cycle of the virus was followed from 1 to 30 h post-infection (p.i.). It was surprising to observe the swift growth of this human virus in Vero cells. Within the first hour of infection, the most obvious ultrastructural change was the proliferation of the Golgi complexes and related vesicles accompanied by swelling of some of the trans -Golgi sacs. Extracellular virus particles were present by 5 h p.i. in about 5 % of the cells and this increased dramatically to about 30 % of the cell population within an hour (6 h p.i.). Swollen Golgi sacs contained virus nucleocapsids at different stages of maturation. These virus precursors were also in large vacuoles and in close association with membrane whorls. The membrane whorls could be the replication complexes, since they appeared rather early in the replication cycle. As infection progressed from 12 to 21 h p.i., the cytoplasm of the infected cells was filled with numerous large, smooth-membraned vacuoles containing a mixture of mature virus and spherical cores. Several of these vacuoles were close to the cell periphery, ready to export out the mature progeny virus particles via exocytosis. By 24 to 30 h p.i., crystalline arrays of the extracellular virus particles were seen commonly at the cell surface.
Molecular determinants of plaque size as an indicator of dengue virus attenuation
Publisher: Springer Science and Business Media LLC
Date: 17-05-2016
DOI: 10.1038/SREP26100
Abstract: The development of live viral vaccines relies on empirically derived phenotypic criteria, especially small plaque sizes, to indicate attenuation. However, while some candidate vaccines successfully translated into licensed applications, others have failed safety trials, placing vaccine development on a hit-or-miss trajectory. We examined the determinants of small plaque phenotype in two dengue virus (DENV) vaccine candidates, DENV-3 PGMK30FRhL3, which produced acute febrile illness in vaccine recipients and DENV-2 PDK53, which has a good clinical safety profile. The reasons behind the failure of PGMK30FRhL3 during phase 1 clinical trial, despite meeting the empirically derived criteria of attenuation, have never been systematically investigated. Using in vitro, in vivo and functional genomics approaches, we examined infections by the vaccine and wild-type DENVs, in order to ascertain the different determinants of plaque size. We show that PGMK30FRhL3 produces small plaques on BHK-21 cells due to its slow in vitro growth rate. In contrast, PDK53 replicates rapidly, but is unable to evade antiviral responses that constrain its spread hence also giving rise to small plaques. Therefore, at least two different molecular mechanisms govern the plaque phenotype determining which mechanism operates to constrain plaque size may be more informative on the safety of live-attenuated vaccines.
The 2007 dengue outbreak in Singapore
Publisher: Cambridge University Press (CUP)
Date: 10-02-2010
Lack of association of dengue activity with haze
Publisher: Cambridge University Press (CUP)
Date: 07-04-2010
DOI: 10.1017/S0950268810000683
Abstract: Dengue activity depends on fluctuations in Aedes populations which in turn are known to be influenced by climate factors including temperature, humidity and rainfall. It has been hypothesized that haze may reduce dengue transmission. Due to its geographical location Singapore suffers almost every year from hazes caused by wildfires from Indonesia. Such hazes have a significant impact on pollution indexes in Singapore. We set out to study the relationship of dengue activity and haze (measured as pollution standard index) in Singapore, using ARIMA models. We ran different univariate models, each encompassing a different lag period for the effects of haze and temperature (from lag 0 to lag 12 weeks). We analysed the data on a natural logarithmic scale to stabilize the variance and improve the estimation. No association between dengue activity and haze was found. Our findings do not lend support to the hypothesis that haze is associated with reduced dengue activity in Singapore.
Early events of SARS coronavirus infection in vero cells
Publisher: Wiley
Date: 04-09-2003
DOI: 10.1002/JMV.10499
An Adjuvant for the Induction of Potent, Protective Humoral Responses to an H5N1 Influenza Virus Vaccine with Antigen-Sparing Effect in Mice
Publisher: American Society for Microbiology
Date: 09-2010
DOI: 10.1128/JVI.00596-10
Abstract: Intramuscular administration of inactivated influenza virus vaccine is the main vaccine platform used for the prevention of seasonal influenza virus infection. In clinical trials, inactivated H5N1 vaccines have been shown to be safe and capable of eliciting immune correlates of protection. However, the H5N1 vaccines are poorly immunogenic compared to seasonal influenza virus vaccines. Needle-free vaccination would be more efficient and economical in a pandemic, and the development of an effective and safe mucosal adjuvant will be an important milestone. A stabilized chemical analog of double-stranded RNA, PIKA, was previously reported to be a potent mucosal adjuvant in a murine model. While PIKA stimulates dendritic cells in vitro , little was known about its receptor and adjuvanting mechanism in vivo . In this study, we demonstrated that the immunostimulatory effect of PIKA resulted in an increased number of mature antigen-presenting cells, with the induction of proinflammatory cytokines at the inoculation site. In addition, coadministration of PIKA with a poorly immunogenic H5N1 subunit vaccine led to antigen sparing and quantitative and qualitative improvements of the immune responses over those achieved with an unadjuvanted vaccine in mice. The adjuvanted vaccine provided protection against lethal challenge with homologous and heterologous H5N1 wild-type viruses. Mice lacking functional TLR3 showed diminished cytokine production with PIKA stimulation, diminished antibody responses, and reduced protective efficacy against wild-type virus challenge following vaccination. These data suggest that TLR3 is important for the optimal performance of PIKA as an adjuvant. With its good safety profile and antigen-sparing effect, PIKA could be an attractive adjuvant for use in future pandemics.
Related Organisations
University Of Nottingham
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Eng Eong Ooi.