MVTease: Teasing out the T-cell: detection and characterization
of cytotoxic T-cell responses induced by measles-based vaccines

Project summary

The project combines expertise of the department Viroscience of the Erasmus MC in Rotterdam in detecting virus-specific cellular immune responses with the expertise of Themis Bioscience GmbH in Vienna developing measles-based vaccines against emerging virus infections. The project aims to determine whether measles-based vaccines can induce primary cytotoxic T-cells in the presence of measles virus-specific antibodies.

Chikungunya is a mosquito-borne emerging viral disease with global outbreak potential. Themis has demonstrated immunogenicity and safety of their measles-based chikungunya virus vaccine (MV-CHIK) in phase 1 and phase 2 clinical trials. These trials were performed in healthy adults with pre-existing measles-specific immunity and demonstrated promising induction of chikungunya virus-specific antibodies. Measles-vectored vaccines induce substantial T cell responses in animal models, but cell mediated immunity in humans is less well characterized. This project addresses the fundamental and innovative question whether measles-based vaccines are able to induce a functional primary virus-specific cytotoxic T-cell (CTL) response to a foreign antigen in measles-immune clinical trial participants. We will use MV-CHIK as a model system to assess whether measles-based vaccines can induce primary CTL responses, by measuring and characterizing CHIKV-specific CTLs in peripheral blood mononuclear cells collected by Themis in clinical trials. This proposal represents a proof-of-concept project undertaken primarily to acquire new knowledge of the foundations underlying immunity induced by measles-based vaccines against emerging viruses, without direct commercial application or use in view.

The data generated in this project will support the measles vaccine platform for development of novel vaccines against emerging diseases, underlining its relevance to the Life Sciences & Health roadmap. In addition, the developed methodology will be directly transferable to detection and characterization of virus-specific T-cell responses in other models.