MVA MERS S(Ludwig-Maximilians-Universität München)

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) was formed to evaluate the safety and other key features of new platform technology vaccines. This manuscript provides an overview of Modified Vaccinia virus Ankara (MVA)-vectored vaccines and reviews molecular and biological key features of this platform. In particular, this review aims to provide fundamental information about the promising candidate vaccine MVA-MERS-S which has been evaluated successfully in different preclinical animal models and has undergone clinical testing including a phase Ib study involving more than 170 participants. Infectious diseases continue to be a major cause of human death worldwide. In this context, emerging zoonotic infectious diseases pose a particular challenge for public health systems. In the last two decades, three different respiratory coronaviruses, including the Middle East respiratory syndrome Coronavirus (MERS-CoV) have emerged. For many years, safe and efficacious vaccines have been a major tool to combat infectious diseases. Here, we report on a promising candidate vaccine (MVA-MERS-S) against MERS-CoV based on MVA. Upon application, MVA-MERS-S has been well tolerated and immunogenic, inducing both, cellular and humoral immune responses in different animal models and humans. We demonstrate that the MVA vector platform, with the example of MVA-MERS-S, is a viable and effective tool for producing safe, immunogenic, and efficient vaccines against emerging infectious diseases.

Licensed vaccines against the Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging pathogen of concern, are lacking. The modified vaccinia virus Ankara vector-based vaccine MVA-MERS-S, expressing the MERS-CoV-spike glycoprotein (MERS-S), is one of 3 candidate vaccines in clinical development and elicits robust humoral and cellular immunity. Here, we identified for the first time a MERS-S–specific CD8+ T-cell epitope in an HLA-A*03:01/HLA-B*35:01-positive vaccinee using a screening assay, intracellular cytokine staining, and in silico epitope prediction. As evidence from MERS-CoV infection suggests a protective role of long-lasting CD8+ T-cell responses, the identification of epitopes will facilitate longitudinal analyses of vaccine-induced T-cell immunity.