A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform

Malczyk, Anna; Kupke, Alexandra; Prüfer, Steffen; Scheuplein, Vivian; Hutzler, Stefan; Kreuz, Dorothea; Beissert, Tim; Bauer, Stefanie; Hubich-Rau, Stefanie; Tondera, Christiane; Eldin, Hosam Shams; Schmidt, Jörg; Vergara‐Alert, Júlia; Süzer, Yasemin; Seifried, Janna; Hanschmann, Kay-Martin; Kalinke, Ulrich; Herold, Susanne; Şahin, Uğur; Cichutek, Klaus; Waibler, Zoe; Eickmann, Markus; Becker, Stephan; Mühlebach, Michael D.

doi:10.1128/jvi.01815-15

Cited by 116 publications

(156 citation statements)

References 88 publications

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“…Of note, an MVA vectored vaccine was highly immunogenic and could significantly reduce the MERS-CoV excretion in dromedary camels (Haagmans et al, 2016). A measles virus vectored vaccine was also highly immunogenic and protective in human DPP4transgenic mice (Malczyk et al, 2015). These results clearly demonstrate the great potential of a live-vectored vaccine.…”

Section: Discussionmentioning

confidence: 75%

A recombinant VSV-vectored MERS-CoV vaccine induces neutralizing antibody and T cell responses in rhesus monkeys after single dose immunization

et al. 2018

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Middle East respiratory syndrome coronavirus (MERS-CoV) has been a highly threatening zoonotic pathogen since its outbreak in 2012. Similar to SARS-CoV, MERS-CoV belongs to the coronavirus family and can induce severe respiratory symptoms in humans, with an average case fatality rate of 35% according to the World Health Organization. Spike (S) protein of MERS-CoV is immunogenic and can induce neutralizing antibodies, thus is a potential major target for vaccine development. Here we constructed a chimeric virus based on the vesicular stomatitis virus (VSV) in which the G gene was replaced by MERS-CoV S gene (VSVΔG-MERS). The S protein efficiently incorporated into the viral envelope and mediated cell entry through binding its receptor, human DPP4. Knockdown of clathrin expression by siRNA drastically abrogated the infection of VSVΔG-MERS in Vero cells. Furthermore, in animal studies, the recombinant virus induced neutralizing antibodies and T cell responses in rhesus monkeys after a single intramuscular or intranasal immunization dose. Our findings indicate the potential of the chimeric VSVΔG-MERS as a rapid response vaccine candidate against emerging MERS-CoV disease.

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Section: Discussionmentioning

confidence: 75%

A recombinant VSV-vectored MERS-CoV vaccine induces neutralizing antibody and T cell responses in rhesus monkeys after single dose immunization

et al. 2018

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“…Recombinant measles virus was also developed as a vector for MERS‐CoV vaccine, using the S antigen either full‐length S antigen (expressed on infected cell surfaces) or soluble version of S antigen (secreted from the infected cells), lacking transmembrane and cytoplasmic domains . It was tested in immunocompromised mice, vaccinated twice with a month interval.…”

Section: Current Mers‐cov Vaccine Candidates Under Developmentmentioning

confidence: 99%

“…However, if the same experimental settings were used in this assay, sera from different sources (eg, mice, NHPs, camels, or humans) or from different vaccine platforms (DNA, proteins, viral vectors) can be compared by reporting VNT. For example, MV‐based vaccine, given twice to mice, induced lower VNT than MVA‐based vaccine, given twice to mice (1000 and 2000 VNT, respectively), when VERO cells, EMC/2012 isolate, and other settings were the same in the assay …”

Section: Current Mers‐cov Vaccine Candidates Under Developmentmentioning

confidence: 99%

Vaccines against Middle East respiratory syndrome coronavirus for humans and camels

Alharbi

2016

Reviews in Medical Virology

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Middle East respiratory syndrome coronavirus (MERS-CoV) is caused by a novel betacoronavirus that was isolated in late 2012 in Saudi Arabia. The viral infections have been reported in more than 1700 humans, ranging from asymptomatic or mild cases to severe pneumonia with a mortality rate of 40%. It is well documented now that dromedary camels contract the infection and shed the virus without notable symptoms, and such animals had been infected by at least the early 1980s. The mechanism of camel to human transmission is still not clear, but several primary cases have been associated with camel contact. There is no approved antiviral drug or vaccine against MERS-CoV despite the active research in this area. Vaccine candidates have been developed using various platforms and regimens and have been tested in several animal models. Here, this article reviews the published studies on MERS-CoV vaccines with more focus on vaccines tested in large animals, including camels. It is foreseeable that the 1-health approach could be the best way of tackling the MERS-CoV endemic in the Arabian Peninsula, by using the mass vaccination of camels in the affected areas to block camel to human transmission. Camel vaccines can be developed in a faster time with fewer regulations and lower costs and could clear this virus from the Arabian Peninsula if accompanied by efficient public health measures.

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“…For instance, mice immunized with VEE particles expressing the SARS-CoV glycoprotein provided protection against lethal SARS-CoV challenges [57]. Furthermore, mice were immunized with MV vectors expressing the MERS-CoV glycoprotein, which resulted in induction of T-cell and antibody responses and protection against lethal doses of MERS-CoV [58]. Respiratory syncytial virus (RSV) has also been targeted with recombinant MV vectors by expression of the RSV fusion protein (RSV-F) [39].…”

Section: Self-replicating Rna Virus-based Vaccinesmentioning

confidence: 99%

Replicon RNA Viral Vectors as Vaccines

Lundström¹

2016

Vaccines

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Single-stranded RNA viruses of both positive and negative polarity have been used as vectors for vaccine development. In this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. Administration of replicon RNA vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. Immunization of mice, chicken, pigs and primates with virus-like particles, naked RNA or layered DNA/RNA plasmids has provided protection against challenges with lethal doses of infectious agents and administered tumor cells. Both prophylactic and therapeutic efficacy has been achieved in cancer immunotherapy. Moreover, recombinant particles and replicon RNAs have been encapsulated by liposomes to improve delivery and targeting. Replicon RNA vectors have also been subjected to clinical trials. Overall, immunization with self-replicating RNA viruses provides high transient expression levels of antigens resulting in generation of neutralizing antibody responses and protection against lethal challenges under safe conditions.

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A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform

Cited by 116 publications

References 88 publications

A recombinant VSV-vectored MERS-CoV vaccine induces neutralizing antibody and T cell responses in rhesus monkeys after single dose immunization

A recombinant VSV-vectored MERS-CoV vaccine induces neutralizing antibody and T cell responses in rhesus monkeys after single dose immunization

Vaccines against Middle East respiratory syndrome coronavirus for humans and camels

Replicon RNA Viral Vectors as Vaccines

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