Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches

Okba, Nisreen M.A.; Raj, V. Stalin; Haagmans, Bart L.

doi:10.1016/j.coviro.2017.03.007

Cited by 62 publications

(66 citation statements)

References 80 publications

(109 reference statements)

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“…Currently, no MERS-CoV-specific or licensed human vaccines are available (Modjarrad et al, 2016;World Health Organization, 2017c). Several human vaccine candidates for coronaviruses, including MERS-CoV, are at various stages of development and five general vaccine technology platforms have been developed and target the MERS-CoV spike protein (Modjarrad et al, 2016;Okba et al, 2017). WHO, the Ministry of Health in KSA and the International Vaccine Institute (IVI) have continued to further align efforts to develop coronavirus vaccines (Excler et al, 2016) and the Coalition for Epidemic Preparedness and Innovation (CEPI) has included MERS-CoV as one of three priority pathogens for financing of a human vaccine.…”

Section: Vaccines For Humansmentioning

confidence: 99%

MERS: Progress on the global response, remaining challenges and the way forward

et al. 2018

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This article summarizes progress in research on Middle East Respiratory Syndrome (MERS) since a FAO-OIE-WHO Global Technical Meeting held at WHO Headquarters in Geneva on 25-27 September 2017. The meeting reviewed the latest scientific findings and identified and prioritized the global activities necessary to prevent, manage and control the disease. Critical needs for research and technical guidance identified during the meeting have been used to update the WHO R&D MERS-CoV Roadmap for diagnostics, therapeutics and vaccines and a broader public health research agenda. Since the 2017 meeting, progress has been made on several key actions in animal populations, at the animal/human interface and in human populations. This report also summarizes the latest scientific studies on MERS since 2017, including data from more than 50 research studies examining the presence of MERS-CoV infection in dromedary camels.

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Section: Vaccines For Humansmentioning

confidence: 99%

MERS: Progress on the global response, remaining challenges and the way forward

et al. 2018

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“…Despite potential threat for the large scale outbreaks of SARS and MERS, no drugs or vaccines of therapeutics modality are available so far. Therefore, understating of the molecular mechanism of viral pathogenesis may be exploited for the development of anti-viral drugs and vaccines [36,37].…”

Section: Introductionmentioning

confidence: 99%

NMR structure and localization of a large fragment of the SARS-CoV fusion protein: Implications in viral cell fusion

Mahajan

Chatterjee

Kannaian

et al. 2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The lethal Coronaviruses (CoVs), Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV) and most recently Middle East Respiratory Syndrome Coronavirus, (MERS-CoV) are serious human health hazard. A successful viral infection requires fusion between virus and host cells carried out by the surface spike glycoprotein or S protein of CoV. Current models propose that the S2 subunit of S protein assembled into a hexameric helical bundle exposing hydrophobic fusogenic peptides or fusion peptides (FPs) for membrane insertion. The N-terminus of S2 subunit of SARS-CoV reported to be active in cell fusion whereby FPs have been identified. Atomic-resolution structure of FPs derived either in model membranes or in membrane mimic environment would glean insights toward viral cell fusion mechanism. Here, we have solved 3D structure, dynamics and micelle localization of a 64-residue long fusion peptide or LFP in DPC detergent micelles by NMR methods. Micelle bound structure of LFP is elucidated by the presence of discretely folded helical and intervening loops. The C-terminus region, residues F42-Y62, displays a long hydrophobic helix, whereas the N-terminus is defined by a short amphipathic helix, residues R4-Q12. The intervening residues of LFP assume stretches of loops and helical turns. The N-terminal helix is sustained by close aromatic and aliphatic sidechain packing interactions at the non-polar face. N{H}NOE studies indicated dynamical motion, at ps-ns timescale, of the helices of LFP in DPC micelles. PRE NMR showed that insertion of several regions of LFP into DPC micelle core. Together, the current study provides insights toward fusion mechanism of SARS-CoV.

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“…[84] Because airway immune responses may be key to preventing the establishment of human MERS-CoV infection, localised deposition of an aerosolised vaccine could prove useful. [84] A number of vaccine platforms and payloads have proceeded although progress has been challenged by the need for animal models that suitably reconstitute human lower respiratory tract disease to show evidence of a preventative effect. [85,86] Some candidates have progressed to clinical trials.…”

Section: Prevention and Treatmentmentioning

confidence: 99%

“…[85,86] Some candidates have progressed to clinical trials. [87,88] The spike protein and RBD elicit neutralizing antibody responses and have been employed as the payload for a number of platforms [84,89,90] including DNA vaccines, [91], modified vaccinia virus Ankara [92,93], measles virus, [93][94][95][96] human-[25, 97] and chimpanzee-adenovirus-based vectors. [95] There are also Venezuelan equine encephalitis replicons expressing nucleocapsid, [97] nanoparticles, [98] and structural and non-structural deletion mutants of MERS-CoV.…”

Section: Prevention and Treatmentmentioning

confidence: 99%

An opportunistic Pathogen Afforded Ample Opportunities: Middle East Respiratory Syndrome Coronavirus

Mackay

Arden

2017

Preprint

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The human coronaviruses (CoV) include HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1, some known for decades. The severe acute respiratory syndrome (SARS) CoV briefly emerged into the human population but was controlled. In 2012 another novel severely human pathogenic CoV -Middle Eastern Respiratory Syndrome (MERS)-CoV was identified in the Kingdom of Saudi Arabia, where 80% of over 2,000 human cases have been recorded across five years. Targeted research remains key to developing control strategies for MERS-CoV, a cause of mild illness in its camel reservoir. A new therapeutic toolbox being developed in response to MERS is also teaching us more about how CoVs cause disease. Travel-related cases continue to challenge the world's surveillance and response capabilities and more data are needed to understand unexplained primary transmission. Signs of genetic change have been recorded but it remains unclear whether any impact on clinical disease. How camels came to carry the virus remains academic to the control of MERS. To date, human-to-human transmission has been inefficient, but virus surveillance, characterisation and reporting are key to responding to any future change. MERS-CoV is not currently a pandemic threat; it is spread mainly with the aid of human habit and error.

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Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches

Cited by 62 publications

References 80 publications

MERS: Progress on the global response, remaining challenges and the way forward

MERS: Progress on the global response, remaining challenges and the way forward

NMR structure and localization of a large fragment of the SARS-CoV fusion protein: Implications in viral cell fusion

An opportunistic Pathogen Afforded Ample Opportunities: Middle East Respiratory Syndrome Coronavirus

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