Abstract
Emerging infectious diseases represent an increasing threat to human and animal health. Therefore, safe and effective vaccines that could be available within a short time frame after an outbreak are required for adequate prevention and control. Here, we developed a robust and versatile self-assembling multimeric protein scaffold particle (MPSP) vaccine platform using lumazine synthase (LS) from Aquifex aeolicus. This scaffold allowed the presentation of peptide epitopes by genetic fusion as well as the presentation of large antigens by bacterial superglue-based conjugation to the pre-assembled particle. Using the orthobunyavirus model Schmallenberg virus (SBV) we designed MPSPs presenting major immunogens of SBV and assessed their efficacy in a mouse model as well as in cattle, a target species of SBV. All prototype vaccines conferred protection from viral challenge infection and the multivalent presentation of the selected antigens on the MPSP markedly improved their immunogenicity compared to the monomeric subunits. Even a single shot vaccination protected about 80% of mice from an otherwise lethal dose of SBV. Most importantly, the MPSPs induced a virtually sterile immunity in cattle. Altogether, LS represents a promising platform for modular and rapid vaccine design.
Highlights
Emerging infectious diseases represent an increasing threat for human and animal health as a consequence of economic development, increasing global commerce, travel and the ongoing disruption of ecologies
We present the development of a modular vaccine platform based on the lumazine synthase from Aquifex aeolicus
We demonstrate that the lumazine synthase (LS) represents a versatile multimeric scaffold that is suitable for the display of directly fused linear epitopes as well as for large and complex antigens using a protein superglue plug-and-display strategy
Summary
Emerging infectious diseases represent an increasing threat for human and animal health as a consequence of economic development, increasing global commerce, travel and the ongoing disruption of ecologies. Over the last few years, efforts enabling an accelerated production of efficient vaccines were dominated by the development of innovative delivery platforms such as recombinant virus-like particles (VLPs) [10,11] Due to their small size and their multivalent, highly repetitive presentation of antigens, VLPs can induce a very efficient immune response in combination with an outstanding safety profile since they lack viral genomes and are unable to cause any disease [12,13,14]. They are suitable for low-cost and large-scale production without the need for biosafety facilities, which can significantly accelerate manufacturing and regulatory processes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
