Scientific background
Alphaviruses like the human pathogenic chikungunya virus (CHIKV) are of increasing public health concern. The CHIKV has recently spread worldwide, and a further spread is highly likely. The symptoms of an infection include myalgia, arthritis and severe joint pain, which can become chronic and persist for years. Therefore, in our group we have been working on trans-amplifying RNA (taRNA) as a CHIKV vaccine candidate. This vaccine consists of two RNAs: the first is a synthetic mRNA, which encodes the CHIKV non-structural proteins (replicase). The second trans-replicon (TR) RNA encodes for the antigen, the CHIKV envelope proteins. The TR-RNA can be efficiently amplified by the replicase in trans leading to a high antigen expression. Consequently, small RNA amounts can elicit potent immune responses.
PhD project description
This project aims to improve the immunogenicity of our CHIKV taRNA vaccine candidate by the usage of virus-like particles (VLPs). VLPs closely resemble the virus structure and due to the repetitive, high-density display of epitopes strong immune responses can be induced. The combination of taRNA and VLPs might unleash the potential of mRNA based VLP vaccines with a unique combination of high expression profiles and presentation of epitopes in their native state as virions. This may allow single-shot vaccination in opposite to prime-boost regimen currently required for mRNA vaccines. For this purpose, different vaccine candidates will be designed and the immune response to these will be characterized within the PhD project. With these studies we aim to understand the immune response to in situ produced VLPs and to establish a highly immunogenic taRNA-VLP platform.
Required profile of the candidate
The ideal candidate should have:
A background in immunology and/or virology
Experience in cell culture
Experience in working with RNA
Experience with in vivo work using mouse models (as a plus)
We are looking for individuals who are enthusiastic about scientific research, highly motivated, and eager to contribute to the development of innovative interventions. Join our dynamic and international research team and contribute to groundbreaking work in the field of vaccinology!
Publications relevant to the project
Schmidt C, Haefner E, Gerbeth J, Beissert T, Sahin U, Perkovic M, Schnierle BS. A taRNA vaccine candidate induces a specific immune response that protects mice against Chikungunya virus infections. Mol Ther Nucleic Acids. 2022 May 2;28:743-754. doi: 10.1016/j.omtn.2022.04.036
Perkovic M, Gawletta S, Hempel T, Brill S, Nett E, Sahin U, Beissert T. A trans-amplifying RNA simplified to essential elements is highly replicative and robustly immunogenic in mice. Mol Ther. 2023 Jun 7;31(6):1636-1646. doi: 10.1016/j.ymthe.2023.01.019
Yıldız A, Răileanu C, Beissert T. Trans-Amplifying RNA: A Journey from Alphavirus Research to Future Vaccines. Viruses. 2024 Mar 25;16(4):503. doi: 10.3390/v16040503
Mohsen, M.O., Bachmann, M.F. Virus-like particle vaccinology, from bench to bedside. Cell Mol Immunol 19, 993–1011 (2022). https://doi.org/10.1038/s41423-022-00897-8
Akahata, W., Yang, ZY., Andersen, H. et al. A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. Nat Med 16, 334–338 (2010). https://doi.org/10.1038/nm.2105