Displaying all 5 publications

  1. Yong CY, Ong HK, Yeap SK, Ho KL, Tan WS
    Front Microbiol, 2019;10:1781.
    PMID: 31428074 DOI: 10.3389/fmicb.2019.01781
    Middle East respiratory syndrome (MERS) is a deadly viral respiratory disease caused by MERS-coronavirus (MERS-CoV) infection. To date, there is no specific treatment proven effective against this viral disease. In addition, no vaccine has been licensed to prevent MERS-CoV infection thus far. Therefore, our current review focuses on the most recent studies in search of an effective MERS vaccine. Overall, vaccine candidates against MERS-CoV are mainly based upon the viral spike (S) protein, due to its vital role in the viral infectivity, although several studies focused on other viral proteins such as the nucleocapsid (N) protein, envelope (E) protein, and non-structural protein 16 (NSP16) have also been reported. In general, the potential vaccine candidates can be classified into six types: viral vector-based vaccine, DNA vaccine, subunit vaccine, nanoparticle-based vaccine, inactivated-whole virus vaccine and live-attenuated vaccine, which are discussed in detail. Besides, the immune responses and potential antibody dependent enhancement of MERS-CoV infection are extensively reviewed. In addition, animal models used to study MERS-CoV and evaluate the vaccine candidates are discussed intensively.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus
  2. Ahn M, Anderson DE, Zhang Q, Tan CW, Lim BL, Luko K, et al.
    Nat Microbiol, 2019 05;4(5):789-799.
    PMID: 30804542 DOI: 10.1038/s41564-019-0371-3
    Bats are special in their ability to host emerging viruses. As the only flying mammal, bats endure high metabolic rates yet exhibit elongated lifespans. It is currently unclear whether these unique features are interlinked. The important inflammasome sensor, NLR family pyrin domain containing 3 (NLRP3), has been linked to both viral-induced and age-related inflammation. Here, we report significantly dampened activation of the NLRP3 inflammasome in bat primary immune cells compared to human or mouse counterparts. Lower induction of apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and secretion of interleukin-1β in response to both 'sterile' stimuli and infection with multiple zoonotic viruses including influenza A virus (-single-stranded (ss) RNA), Melaka virus (PRV3M, double-stranded RNA) and Middle East respiratory syndrome coronavirus (+ssRNA) was observed. Importantly, this reduction of inflammation had no impact on the overall viral loads. We identified dampened transcriptional priming, a novel splice variant and an altered leucine-rich repeat domain of bat NLRP3 as the cause. Our results elucidate an important mechanism through which bats dampen inflammation with implications for longevity and unique viral reservoir status.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/genetics; Middle East Respiratory Syndrome Coronavirus/immunology
  3. Nyon MP, Du L, Tseng CK, Seid CA, Pollet J, Naceanceno KS, et al.
    Vaccine, 2018 03 27;36(14):1853-1862.
    PMID: 29496347 DOI: 10.1016/j.vaccine.2018.02.065
    Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377-588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals. To prepare for the manufacture and first-in-human testing of the vaccine, we have developed a process to stably produce the recombinant MERS S377-588 protein in Chinese hamster ovary (CHO) cells. To accomplish this, we transfected an adherent dihydrofolate reductase-deficient CHO cell line (adCHO) with a plasmid encoding S377-588 fused with the human IgG Fc fragment (S377-588-Fc). We then demonstrated the interleukin-2 signal peptide-directed secretion of the recombinant protein into extracellular milieu. Using a gradually increasing methotrexate (MTX) concentration to 5 μM, we increased protein yield by a factor of 40. The adCHO-expressed S377-588-Fc recombinant protein demonstrated functionality and binding specificity identical to those of the protein from transiently transfected HEK293T cells. In addition, hCD26/dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with AddaVax-adjuvanted S377-588-Fc could produce neutralizing antibodies against MERS-CoV and survived for at least 21 days after challenge with live MERS-CoV with no evidence of immunological toxicity or eosinophilic immune enhancement. To prepare for large scale-manufacture of the vaccine antigen, we have further developed a high-yield monoclonal suspension CHO cell line.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/immunology*
  4. Al-Tawfiq JA, Memish ZA
    Am J Infect Control, 2019 Oct;47(10):1167-1170.
    PMID: 31128983 DOI: 10.1016/j.ajic.2019.04.007
    BACKGROUND: An important emerging respiratory virus is the Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV had been associated with a high case fatality rate especially among severe cases.

    METHODS: This is a retrospective analysis of reported MERS-CoV cases between December 2016 and January 2019, as retrieved from the World Health Organization. The aim of this study is to examine the epidemiology of reported cases and quantify the percentage of health care workers (HCWs) among reported cases.

    RESULTS: There were 403 reported cases with a majority being men (n = 300; 74.4%). These cases were reported from Lebanon, Malaysia, Oman, Qatar, Saudi Arabia, and United Arab Emirates. HCWs represented 26% and comorbidities were reported among 71% of non-HCWs and 1.9% among HCWs (P < .0001). Camel exposure and camel milk ingestion were reported in 64% each, and the majority (97.8%) of those with camel exposures had camel milk ingestion. There were 58% primary cases and 42% were secondary cases. The case fatality rate was 16% among HCWs compared with 34% among other patients (P = .001). The mean age ± SD was 47.65 ± 16.28 for HCWs versus 54.23 ± 17.34 for non-HCWs (P = .001).

    CONCLUSIONS: MERS-CoV infection continues to have a high case fatality rate and a large proportion of patients were HCWs. Further understanding of the disease transmission and prevention mainly in health care settings are needed.

    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus
  5. Park S, Park JY, Song Y, How SH, Jung KS, Respiratory Infections Assembly of the APSR
    Respirology, 2019 Jun;24(6):590-597.
    PMID: 30985968 DOI: 10.1111/resp.13558
    In past decades, we have seen several epidemics of respiratory infections from newly emerging viruses, most of which originated in animals. These emerging infections, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and the pandemic influenza A(H1N1) and avian influenza (AI) viruses, have seriously threatened global health and the economy. In particular, MERS-CoV and AI A(H7N9) are still causing infections in several areas, and some clustering of cases of A(H5N1) and A(H7N9) may imply future possible pandemics. Additionally, given the inappropriate use of antibiotics and international travel, the spread of carbapenem-resistant Gram-negative bacteria is also a significant concern. These infections with epidemic or pandemic potential present a persistent threat to public health and a huge burden on healthcare services in the Asia-Pacific region. Therefore, to enable efficient infection prevention and control, more effective international surveillance and collaboration systems, in the context of the 'One Health' approach, are necessary.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus
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