Development of a Modular Vaccine Platform for Multimeric Antigen Display Using an Orthobunyavirus Model

Vaccines

Jean-Christophe Audonnet¹  Ronen Tchelet²  Martin Beer³  Andrea Aebischer³  Patricia König³  Kerstin Wernike³  Kati Franzke³  Jeroen Kortekaas⁴  Paul J. Wichgers Schreur⁴  Markku Saloheimo⁵  Marilyn Wiebe⁵  Marika Vitikainen⁵ 

[1] Boehringer Ingelheim Animal Health, 69800 Saint-Priest, France;Dyadic Netherland B.V., 6709 PA Wageningen, The Netherlands;Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, Germany;Laboratory of Virology, Wageningen Bioveterinary Research, 8221 RA Lelystad, The Netherlands;VTT Technical Research Centre of Finland Ltd., 02150 Espoo, Finland;

关键词: emerging infectious disease;    zoonosis;    modular vaccine;    epitope;    lumazine synthase;    Schmallenberg virus;   

DOI  :  10.3390/vaccines9060651

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown