New Ebola research project at LMU
LMU virologist Gerd Sutter is engaged in identifying candidate antigens for use in a vaccine that could protect against infection with all subtypes of the Ebola virus, including that responsible for the current epidemic in West Africa.
Neither licensed vaccines which confer protective immunity nor targeted therapeutics specifically directed against the Ebola virus (EBOV) are yet available. This lack of pre- and post-exposure treatments partly explains why the ongoing outbreak in West Africa has not yet been brought under control. First identified as a human pathogen in Central Africa in 1976, the virus is known to be transmitted via direct contact with body fluids of infected persons. EBOV causes hemorrhagic fever and ultimately leads to multiple organ failure. But infected individuals present with more generalized symptoms, such as high fever, muscle and abdominal pain, vomiting and diarrhea, which may be followed by profuse internal and external bleeding. According to the World Health Organization the average mortality rate is well over 50%. The current epidemic, during which some 10,000 people have already been infected, is by far the largest since the virus was first discovered nearly 40 years ago.
At the German Center for Infectious Disease Research (DZIF), an Ebola Consortium (EBOKON) has initiated several research projects devoted to the pathobiology and immunology of EBOV. One of these projects is headed by Gerd Sutter, Professor of Virology at LMU’s Institute for Infectious Diseases and Zoonoses.
Sutter’s goal is to develop an effective vaccine against the pathogen, based on the use of the so-called Modified Vaccinia virus Ankara (MVA), a non-replicating derivative of the smallpox vaccine virus, as a carrier particle for EBOV antigens. MVA was first successfully utilized as an anti-smallpox vaccine over 30 years ago. Today MVA is employed in vaccine research and development all over the world, in studies of ways to induce specific immunological responses not only to viruses but also to bacteria, parasites or cancer-specific antigens. With the aid of molecular biological techniques, researchers insert genetic information from other, pathogenic viruses – in this case EBOV – into the genome of the MVA virus. As a result, the EBOV proteins encoded by these genes are co-produced by the MVA virus. When these MVA particles are injected into human subjects, the EBOV antigens can provoke the formation of antibodies and so-called T cells that provide persistent immunity to infection by the pathogen.
According to the German Center for Infection Research, two promising vaccine candidates have been developed, which are directed against two subtypes of the EBOV. “It is thought that there are four immunologically distinct subtypes, so that it will be necessary to prepare multivalent anti-Ebola cocktails that can provide active protection against all four variants,” says Gerd Sutter. “One of the great advantages of MVA-based vaccines is that the scaffold has a high packing capacity: We can insert several extra genes encoding foreign viral antigens into the MVA genome.”
According to the DZIF, the goal of the LMU project is to contribute to the development of a broadly protective Ebola-virus-specific vaccine, which can be produced and made available for clinical testing within a relatively short time.