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Hypothesized transmission of MERS-CoV from animal hosts to humans (A) MERS-CoV is potentially transmitted by infected bats to African one-humped camels, which are often imported exported to the Arabian Peninsula. (B) Vaccination of one-humped camels could therefore prevent further transmission of the virus to humans and subsequent human-to-human transmission if one-humped camels are indeed the primary route of infection for humans.
Source publication
The recent emergence of Middle East respiratory syndrome (MERS) highlights the need to engineer new methods for expediting vaccine development against emerging diseases. However, several obstacles prevent pursuit of a licensable MERS vaccine. First, the lack of a suitable animal model for MERS complicates the in vivo testing of candidate vaccines....
Contexts in source publication
Context 1
... genomic study indeed revealed the presence of several genetic variants of MERS-CoV in individual one-humped camels, whereas MERS-CoV in humans exposed to these one-humped camels appears to be infected with clonal MERS-CoV populations [44]. As one-humped camels are frequently exported from Africa to the Arabian Peninsula of Western Asia, an animal native to Africa could be transmitting MERS-CoV to one- humped camels prior to exportation (Figure 1). ...
Context 2
... bat-origin hypothesis is based on betacoronavirus phylogeny and receptor usage [55,56,[64][65][66][67] and isolation of MERS-CoV from one individual Egyptian tomb bat (Taphozous perforatus) [66]. However, these studies are suggestive and epidemiological evidence of bat-to-human or bat-to-one-humped camel transmission of MERS-CoV ( Figure 1A) has yet to be gathered [68]. ...
Context 3
... one-humped camels are the reservoir of MERS-CoV (see above), then their vaccination against MERS-CoV infection may provide an intervention opportunity ( Figure 1B). Indeed, three one-humped camels, inoculated by intranasal, intratracheal, and conjunctival routes with MERS-CoV developed benign clinical signs, but shed large quantities of virus from the upper respiratory tract [51]. ...
Similar publications
Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a novel betacoronavirus (MERS coronavirus, MERS-CoV). Since its first emergence in 2012, multiple transmission events of MERS-CoV (dromedary to human and human to human) have been reported, indicating that MERS-CoV has the potential to cause widespread outbreak...
Citations
... The FastVax Design Model by De Groot et al. [28] suggested using computational tools to design and deliver vaccines on demand for biodefense purposes. The Papaneri et al. [29] model provided a pathway for expediting vaccine development against emerging diseases. The Vaccine Ecosystem proposed by Saadatian-Elahi et al. [30] described the main actors involved in vaccine R&D, manufacturing, distribution, procurement, and immunization. ...
... The main differences between the meta-model presented in this work and the models developed in contexts of global health threats, disease outbreaks, epidemics, or pandemics [e.g., 3,28,29] are the longer extension of the value chain, as well as the identification of innovations and mechanisms, which driven by the pandemic and supported by contextual factors, enabled the R&D paradigm shift and consequently made it possible to develop, manufacture, and deliver vaccines at a rapid pace. The cause-effect relationships among these elements are established in the second entity of the meta-model depicted in Fig. 3, known as the innovation causal model. ...
PurposeOver the past decade, successive outbreaks and epidemics of infectious diseases have challenged the emergency preparedness and response systems of global public health institutions, a context in which vaccines have become the centerpiece to strengthening global health security. Nevertheless, vaccine research and development (R&D) is a complex, lengthy, risky, uncertain, and expensive process. Alongside strict, time-consuming regulatory compliance, it takes multiple candidates and many years to register a new vaccine. This is certainly not welcome in a global health crisis such as the COVID-19 pandemic. Therefore, this study aims to understand the R&D paradigm shift in pandemic contexts and its impacts on the value chain of vaccine innovation.Methods
To that end, this paper carried out a systematic literature review and meta-synthesis of 27 articles and reports (2011–2021) that addressed vaccine R&D in contexts of global health threats, disease outbreaks, epidemics, or pandemics.ResultsThe research findings are synthesized in a meta-model, which describes a fast-track R&D for pandemic contexts, its driving forces, innovations, mechanisms, and impacts in the value chain of vaccine innovation.Conclusions
The study demonstrates that, in pandemic contexts, a fast-track R&D process based on close collaboration among regulators, industry, and academia and leveraging enabling technologies can drastically reduce the time required to bring safe, stable, and effective vaccines to market by an average of 11 years compared to the traditional R&D process. Furthermore, pharmacovigilance and rigorous monitoring of real-world evidence became critical to ensuring that quality and safe products were authorized for use during a pandemic.
... A typical vaccine development cycle takes a minimum of ten years from lab research to its approved use after all clinical assessments, making traditional approaches timeconsuming and labor intensive [39,40]. The advent of genome sequencing and high-performance computational technology has made immunoinformatics predictions cost-effective and convenient [41][42][43]. In silico immuno-informatics approaches have reduced the number of experiments needed for vaccine development, and it has been demonstrated to identify protein immunogenic attributes with high efficiency [44][45][46]. ...
Millions of lives have been infected since the SARS-CoV-2 outbreak in 2019. The high human-to-human transmission rate has warranted a need for a vaccine to protect people. Although some vaccines are in use, due to the high mutation rate in the SARS-CoV-2 multiple variants, the current vaccines may not be sufficient to immunize people against new variant threats. One of the emerging concern variants is B1.1.529 (Omicron), which carries ~ 30 mutations in the Spike protein (S) of SARS-CoV-2 and is predicted to evade antibody recognition even from vaccinated people. We used a structure-based approach and an epitope prediction server to develop a Multi-Epitope based Subunit Vaccine (MESV) involving SARS-CoV-2 B1.1.529 variant spike glycoprotein. The predicted epitope with better antigenicity and non-toxicity was used for designing and predicting vaccine construct features and structure models. In addition, the MESV construct In silico cloning in the pET28a expression vector predicted the construct to be highly translational. The proposed MESV vaccine construct was also subjected to immune simulation prediction and was found to be highly antigenic and elicit a cell-mediated immune response. Therefore, the proposed MESV in the present study has the potential to be evaluated further for vaccine production against the newly identified B1.1.529 (Omicron) variant of concern.
Supplementary information:
The online version contains supplementary material available at 10.1007/s11224-022-02027-6.
... The process of vaccine development is laborious and involves several stages [6] . However, when, on March 11 th , 2020, COVID-19 was declared to be a global pandemic by the World Health Organization (WHO), it was recommended that some of the usual stages of vaccine development be skipped to accelerate development and regulatory assessment, approval, manufacturing and quality control. ...
BioNTech/Pfizer’s Comirnaty and Moderna’s SpikeVax vaccines consist in mRNA encapsulated in lipid nanoparticles (LNPs). The modularity of the delivery platform and the manufacturing possibilities provided by microfluidics let them look like an instant success, but they are the product of decades of intense research. There is a multitude of considerations to be made when designing an optimal mRNA-LNP vaccine. Herein, we provide a brief overview of what is presently known and what still requires investigation to optimize mRNA LNP vaccines. Lastly, we give our perspective on the engineering of 3D bioprinted validation systems that will allow faster, cheaper, and more predictive vaccine testing in the future compared with animal models.
... However, it is worth noting that the higher transmissibility but low number of cases in South Korea may be attributed to the timely and effective control measures taken by the government. Papaneri et al. [36] observed that possibly, MERS-CoV was transmitted to a camel in Africa by infected bats and then exported to the Arabian Peninsula via trade channels. Thereafter, the virus was transmitted to humans via direct or indirect contact with camels, with subsequent widespread transmission from person-to-person. ...
Background
In this study, we aimed to quantify the contribution of different transmission routes of the Middle East respiratory syndrome (MERS) and determine its transmissibility.
Methods
Based on the natural history and transmission features of MERS in different countries, a susceptible-exposed-symptomatic-asymptomatic-recovered/death (SEIARD) model and a multi-route dynamic model (MMDM). The SEIARD model and MMDM were adopted to simulate MERS in South Korea and Saudi Arabia, respectively. Data on reported MERS cases in the two countries were obtained from the World Health Organization. Thereafter, the next generation matrix method was employed to derive the equation for the basic reproduction number (R0), and the model fitting procedure was adopted to calculate the R0 values corresponding to these different countries.
Results
In South Korea, ‘Person-to-Person’ transmission was identified as the main mode of MERS transmission in healthcare settings, while in Saudi Arabia, in addition to ‘Person-to-Person’ transmission, ‘Host-to-Host’ and ‘Host-to-Person’ transmission also occurred under certain scenarios, with camels being the main host. Further, the fitting results showed that the SEIARD model and MMDM fitted the data well. The mean R0 value was 8.59 (95% confidence interval [CI]: 0–28.02) for MERS in South Korea, and for MERS in Saudi Arabia, it was 1.15 and 1.02 (95% CI: 0.86–1.44) for the ‘Person-to-Person’ and ‘Camel-to-Camel’ transmission routes, respectively.
Conclusions
The SEIARD and MMDM model can be used to simulate the transmission of MERS in different countries. Additionally, in Saudi Arabia, the transmissibility of MERS was almost the same among hosts (camels) and humans.
... Another study reported that quinoline and quinazoline Alkaloids such as norquinadoline A, deoxynortryptoquivaline, and deoxytryptoquivaline inhibited three protein targets of SARS-COV-2 and showed excellent pharmacokinetic and safety profiles [23]. Particular medication or vaccine production process requires at least ten years from bench research to approve [24,25]. At the moment, performing computational design and drug discovery can considerably reduce both the cost and the time required for medication development [26]. ...
Numerous deaths worldwide have been caused by the coronavirus pandemic and are currently progressing with successive mutations and a lack of appropriate and definitive treatment. One of the drug targets to control the replication of the virus and treat this disease is to block the ion channel of the virus. This will lead to its death by disturbing the internal balance of the virus. Natural compounds such as alkaloids are usually known as effective compounds due to their medicinal characteristics and easy access to their sources. To this end, more than 3,200 natural alkaloid structures interacted with pentameric ion channels. Alkaloid compounds established significant and stable interactions with the channel. More clearly and in more detail, six alkaloid compounds with the best pharmacokinetics and binding affinity of less than-10.52 kcal/mol were selected as hit and suitable compounds for virus control. The compound of psammaplysin U (NA-1) with a binding affinity of-13.52 kcal/mol and binding free energy of-82.21 kcal/mol established hydrogen interactions with the amino acid of Val 25 in the B chain of the ion channel, which placed the compound at the top of the selected compounds. The molecular dynamics simulation of the ligand-protein complex in the 100 ps trajectory showed that the principal interactions were hydrogen and halogen bonding with the amino acids of Val 25 and Thr 30 in the B chain and A chain, respectively, which could be a suitable inhibitor to combat the COVID-19.
... Фармацевтичні компанії мають мізерний стимул для виробництва вакцини проти MERS-CoV, адже клінічні випробування доволі дорогі, а терміни затвердженого використання препарату становлять 10 років або довше. Втім, користь від розробки безпечної та ефективної вакцини перевищить будь-які витрати (Papaneri A.B. et al., 2015). ...
У науковій монографії викладено сучасне розуміння поняття «персистування
вірусів» і формування повільних, хронічних і латентних інфекцій у сільськогосподарських і диких тварин. Розкриті основні механізми персистування вірусів під час
повільних інфекційних захворювань. Автори, ґрунтуючись на наукових працях (вірусологів, епізоотологів й епідеміологів), виводять загальні закономірності, причини
й передумови виникнення повільних інфекцій, розкривають сучасні відомості про
збудників, клінічний і патолого-анатомічний їхні прояви, епізоотологічні та епідеміологічні особливості, сучасні методи діагностики, специфічної профілактики й
заходи боротьби з найбільш актуальними (переважно зоонозними) повільними інфекціями в рамках підходу «Єдине здоров’я».
Розрахована на спеціалістів районних і обласних управлінь, лікарень ветеринарної медицини, слухачів інститутів і факультетів післядипломного навчання, викладачів та студентів факультетів ветеринарної медицини вищих навчальних аграрних закладів і широке коло практичних фахівців ветеринарної медицини.
... There is also a real possibility that a safe, reliable, and practical vaccine will remain unavailable. Several prior attempts to develop vaccines for human coronaviruses have been unsuccessful (7)(8)(9). In some candidate vaccines, those who developed immunity saw a paradoxical worsening of disease (10). ...
... One promising option to confront this issue is the subunit vaccines harbouring numerous and diverse antigenic elements, allowing to produce an inclusive spectrum of native viral antigens. The process of vaccine development takes at least ten years from bench research to approved vaccine use 9 . Identification of apt elements for developing vaccine immunogens can be promoted using chemistry and topology. ...
Coronavirus disease 2019 (COVID-19) is an acute pneumonic disease, with no prophylactic or specific therapeutical solution. Effective and rapid countermeasure against the spread of the disease’s associated virus, SARS-CoV-2, requires to incorporate the computational approach. In this study, we employed various immunoinformatics tools to design a multi-epitope vaccine polypeptide with the highest potential for activating the human immune system against SARS-CoV-2. The initial epitope set was extracted from the whole set of viral structural proteins. Potential non-toxic and non-allergenic T-cell and B-cell binding and cytokine inducing epitopes were then identified through a priori prediction. Selected epitopes were bound to each other with appropriate linkers, followed by appending a suitable adjuvant to increase the immunogenicity of the vaccine polypeptide. Molecular modelling of the 3D structure of the vaccine construct, docking, molecular dynamics simulations and free energy calculations confirmed that the vaccine peptide had high affinity for Toll-like receptor 3 binding, and that the vaccine-receptor complex was highly stable. As our vaccine polypeptide design captures the advantages of structural epitopes and simultaneously integrates precautions to avoid relevant side effects, it is suggested to be promising for elicitation of an effective and safe immune response against SARS-CoV-2 in vivo.
... Their deletion leads to viruses that are attenuated in their virulence and, therefore, may be developed into candidate vaccines. 179,180 ...
Over the past 16 years, three coronaviruses (CoVs), severe acute respiratory syndrome CoV (SARS-CoV) in 2002, Middle East respiratory syndrome CoV (MERS-CoV) in 2012 and 2015, and SARS-CoV-2 in 2020, have been causing severe and fatal human epidemics. The unpredictability of coronavirus disease-19 (COVID-19) poses a major burden on health care and economic systems across the world. This is caused by the paucity of in-depth knowledge of the risk factors for severe COVID-19, insufficient diagnostic tools for the detection of SARS-CoV-2, as well as the absence of specific and effective drug treatments. While protective humoral and cellular immune responses are usually mounted against these betacoronaviruses, immune responses to SARS-CoV2 sometimes derail towards inflammatory tissue damage, leading to rapid admissions to intensive care units. The lack of knowledge on mechanisms that tilt the balance between these two opposite outcomes poses major threats to many ongoing clinical trials dealing with immunostimulatory or immunoregulatory therapeutics. This review will discuss innate and cognate immune responses underlying protective or deleterious immune reactions against these pathogenic coronaviruses.
... Previous studies on SARS-CoV reveal that vaccines based on the S protein can induce antibodies to block virus binding and fusion or neutralize virus infection [56]. Although to date, there are no certified vaccines available against prior coronaviruses [57,58]. Since there is a similarity between S protein of MERS-CoV and nCoV, it would be great to target nCoV S protein for therapeutic research. ...
Currently, pandemic coronavirus disease 2019 (COVID-19) is the biggest threat to all human beings globally. Till June 8, 2020, it has infected 6,931,000 people and caused 400,857 deaths worldwide. The first case was identified in a patient with influenza-like symptoms along with severe acute respiratory syndrome in Wuhan, China, in December 2019 and now it has spread in more than 200 countries. Since there is no approved cure for this disease until now, there is a lot of mass fear, apprehensions, and questions globally regarding (i) genetic origin and history of the novel coronavirus, (ii) what are the first-line therapies for those who contract this disease, and (iii) what could be the potential vaccine targets. In this short review, we have tried to address these queries in the simplest manner and compiled the history of previous coronaviruses, recent developments in the COVID-19 research, potential future therapeutics, and possible targets to cure the disease.
