23 Apr 2024
LMU researchers are investigating how the yellow fever vaccine works to pave the way for better vaccines against diseases such as Zika, dengue, West Nile, and yellow fever.
Climate change and urbanization are the principal reasons for the worldwide occurrence of vector-borne diseases caused by flaviviruses. A disease is described as vector-borne when a pathogen is transmitted to a host (human or animal) through the sting or bite of a vector (mosquito, fly, tick, flea, etc.). They comprise around 17 percent of all infectious diseases worldwide. The WHO estimates that 80 percent of the world’s population is at risk from one or more vector-borne diseases.
The flavivirus genus includes several human pathogens such as Zika, dengue, West Nile Virus (WNV), and yellow fever, which continue to pose a major threat to global health. LMU is a member of the Yellow4FLAVI (Deconstructing the protective immunity of yellow fever virus 17D to inform flavivirus vaccine design) consortium, which was launched at the beginning of March under the coordination of the Institut Pasteur in Paris. The collaborative project has 13 partner institutions from seven countries and is being supported by the European Union with funding of 8 million euros. Its goal is to study the yellow fever vaccine virus and the highly effective immune response to this vaccine in order to understand the molecular foundations of long-lasting immunity. The participating researchers are combining their expert knowledge in the fields of molecular and structural virology, cell biology, innate and adaptive immunity, clinical immunology, and the social sciences and humanities.
“There are no specific antiviral therapies for the treatment of flavivirus infections,” explains LMU professor Anne Krug. The biomedical scientist from the Institute for Immunology is the leader of a subproject in the consortium. Vaccines are currently the most effective weapon against these viruses, she observes. “However, there are just a few authorized vaccines on the market at present, some of which are suitable only for a subsection of the target population. People who are too old or sick, or who are pregnant, often cannot be vaccinated with them,” says Professor Simon Rothenfußer from the Department of Clinical Pharmacology at LMU University Hospital, who also leads a subproject in the consortium. For this reason, the European Commission has undertaken to finance several large-scale research projects aimed at developing safer and more effective vaccines against various flaviviruses.
Yellow4FLAVI mobilizes international experts to close knowledge gaps about the mechanism of action of the most effective vaccine currently available against the yellow fever virus. YF17D is a vaccine which has proven its safety and long-lasting effectiveness after a single injection. However, the underlying molecular mechanisms have not yet been sufficiently clarified. By investigating the structure of the virus particle in conjunction with the host’s immune response, the researchers plan to decode critical aspects of the immune response to the vaccine with the help of state-of-the-art technology. “We’re creating the framework for a broader based vaccine design that can be employed against various flaviviruses,” says Krug. “In the Yellow4FLAVI consortium, we’re investigating the yellow fever vaccine response from early immune activation and cell communication at the injection site through to the development of immunological memory,” adds Professor Maria Colomé-Tatché from the Biomedical Center at LMU, who is also involved in the consortium.