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Vaccine candidate against MERS coronavirus reveals efficacy in mouse model

10.09.2015

The MERS coronavirus can cause severe, potentially lethal infections in human patients. An authorised vaccine is not available, so far. Researchers at the Paul-Ehrlich-Institut in collaboration with various research groups at the German Center for Infection Research (Deutsches Zentrum für Infektionsforschung (DZIF) have developed a vaccine on the basis of a measles virus vaccine strain. This vaccine is highly immunogenic and challenge experiments indicate protection of vaccinated animals. The Journal of Virology reports on these results in its online edition of 09 September 2015.

During the development of “vaccine platforms” against emerging pathogens such as the MERS coronavirus (MERS CoV), selected genetic sequences of the pathogen are integrated into a vaccine vector, for which extensive clinical experience is available.


Photo taken using transmission electron microscopy (TEM) of released MERS-CoV particles (virions)

Source: National Institute of Allergy and Infectious Diseases (NIAID)

Vaccination with such vectors induces immune response both against the vaccine vector and the pathogen’s antigen, which is encoded in the added genetic sequences. The vector vaccine thus generated can be characterised as a model and platform for other vaccines.

Since the pathogen’s sequence integrated in the vaccine vector can easily be exchanged, other pathogens can be targeted on the basis of this prototypic vector vaccine’s construction. Thereby, the development of a vaccine targeting emerging pathogens during the event of sudden outbreaks of epidemics such as the current Ebola epidemic should be accelerated.

A research team that includes researchers working with Dr Michael Mühlebach at the Paul-Ehrlich-Institut (PEI), head of section “Product Testing of Immunological Medicinal Products for Veterinary Use” of the Division Veterinary Medicine and members of the research group “Oncolytic Measles Viruses and Vaccine Vectors” are currently working on such a vaccine platform.

As vaccine vector or vaccine platform, the scientists are using attenuated measles vaccine viruses. Into the genome of this platform those pathogen’s genes are integrated, which shall induce the desired immune responses. The project is part of the German Centre for Infection Research (DZIF) translational unit “Emerging Infections” and is operated in close collaboration with various research groups including that of Professor Stephan Becker, Institute for Virology of Marburg University, and other sections of the Paul-Ehrlich-Institut.

After identifying the MERS-CoV as the causative agent of the mainly respiratory syndrome, which was first described in 2012 in human patients, the development of a vaccine against MERS was started on the basis of measles vaccine viruses in the PEI and the DZIF. For this purpose, the gene encoding the MERS-CoV envelope glycoprotein was inserted into the genome of a measles virus vaccine strain.

The recombinant measles virus-derived vaccine thus modified was characterised and its identity and stability were demonstrated. Using this vaccine, strong immune responses in mice (development of antibodies and T-cell response) were triggered, which protected the immunised animals during infection with MERS-CoV.

“Our data indicate that such recombinant measles viruses are suitable as a platform for developing vaccines against emerging pathogens”, explained Dr Mühlebach. The developed vector vaccine is a promising candidate for a clinical trial on the road towards developing a MERS vaccine.

Previously, members of the DZIF had already participated in the identification of the MERS coronavirus. “This successful research work shows the significance of such research collaborations, which benefit from the expertise of different groups that complement each other. As a result of such work, we hope that when emerging infectious diseases occur, methods for a rapid diagnosis of the disease will be made available ad hoc, thus leading to a quick development of vaccines that effectively combat this disease”, emphasises Professor Klaus Cichutek, president of the Paul-Ehrlich-Institut.

Background on MERS Coronavirus

In 2012, infections with MERS coronavirus (Middle East respiratory syndrome coronavirus) were diagnosed for the first time. In the meantime, more than 1000 infections were confirmed which had their origin in the Arabian Peninsula, above all, Saudi Arabia. Most recently, South Korea has been affected, where the outbreak has been brought under control in the meantime.

Most of the infections were probably transmitted by camels, but transmissions from human to human are also possible. In human patients, the virus causes severe infections with flu-like symptoms and frequently occurring pneumonia as well as breathing difficulties. Other symptoms include diarrhoea and severe courses of acute kidney failure. The disease takes a lethal course in around 30 percent of the cases. An authorised vaccine is so far not available. Currently, symptomatic treatment is the only option.

Original publication

Malczyk AH, Kupke A, Prüfer S, Scheuplein VA, Hutzler S, Kreuz D, Beissert T, Bauer S, Hubich-Rau S, Tondera C, Eldin HS, Schmidt J, Vergara-Alert J, Süzer Y, Seifried J, Hanschmann KM, Kalinke U, Herold S, Sahin U, Cichutek K, Waibler Z, Eickmann M, Becker S, Mühlebach MD (2015) A highly immunogenic and protective MERS-Coronavirus vaccine based on recombinant MV vaccine platform. J. Virol 2015 epub ahead of print 10.1128/JVI.01815-15

The Paul-Ehrlich-Institut, the Federal Institute for Vaccines and Biomedicines, in Langen near Frankfurt/Main is a senior federal authority reporting to the Federal Ministry of Health (Bundesministerium für Gesundheit, BMG). It is responsible for the research, assessment, and marketing authorisation of biomedicines for human use and immunological veterinary medicinal products. Its remit also includes the authorisation of clinical trials and pharmacovigilance, i.e. recording and evaluation of potential adverse effects. Other duties of the institute include official batch control, scientific advice and inspections. In-house experimental research in the field of biomedicines and life science form an indispensable basis for the manifold tasks performed at the institute. The Paul-Ehrlich-Institut, with its roughly 800 members of staff, also has advisory functions nationally (federal government, federal states (Länder)), and internationally (World Health Organisation, European Medicines Agency, European Commission, Council of Europe etc.).

Weitere Informationen:

http://jvi.asm.org/content/early/2015/09/03/JVI.01815-15.abstract

Dr. Susanne Stöcker | idw - Informationsdienst Wissenschaft

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