Minor differences in the untranslated regions of measles vector additional transcription units are reflected by differential immunogenicity of encoded MERS-CoV Spike antigen.

The recombinant measles virus (MeV) is among those vaccine platform technologies, which are tested for the fast generation of effective vaccines against other pathogens, such as emerging virus diseases. Different live-attenuated vaccine strains have become available as backbones, with few differences. Here, we analyze how minor differences of recombinant Moraten (MV IMPORTANCE: In case of emerging or re-emerging infections, vaccine platform technologies are needed to rapidly develop effective vaccines to aid public healthcare in pandemics. Besides mRNA vaccines, also viral platform technologies, that is, the adenovirus-derived vaccines Vaxzevria and JCOVDEN, have proven to be of immense value during the COVID-19 pandemic. For future pandemics, it is crucial to understand the factors in vector design that modulate immunogenicity. This knowledge allows the tailoring of vaccine vectors to fit specific target product profiles, for example, to build vectors which trigger an accentuated T cell or, alternatively, antibody response against an antigen of interest. Our study using the live-attenuated measles vaccine backbone as a promising example is therefore crucial in demonstrating that very minor differences in the vaccine backbone can alter the antigen expression profile of the vector-antigen system and impact the relative induction of T-cell or antibody responses against the added target antigen.