Evaluation of vector-specific immune responses following a homologous prime boost immunization with the vaccine candidate MVA-MERS-S

Abstract

Middle East Respiratory Syndrome (MERS) is caused by MERS coronavirus (MERS-CoV) associated with a high case-fatality rate of up to 35%. With no specific treatment available and considering the high epidemic potential of MERS-CoV infection, fast and efficient development of a protective vaccine is of great interest. The vaccine candidate MVA-MERS-S was proven safe and immunogenic in small and large animal models as well as in a recent first-in-human phase 1 vaccine trial conducted in this working group. MVA-MERS-S is a viral vector vaccine utilizing the attenuated poxvirus Modified Vaccinia virus Ankara (MVA) which expresses the MERS-S-protein. While MVA has increasingly been used as viral vaccine vector, the influence of anti-vector immunity on the formation of antigen-specific immunity remains poorly understood. The aim of this work was the evaluation of vector-immunity within the scope of a phase 1 trial with the vaccine candidate MVA-MERS-S. Cellular and humoral immune responses to the MVA vector were assessed at different time points post vaccination. To measure MVA vector-specific T cell responses an interferon-γ (IFN-γ) ELISpot assay was established. Anti-vaccinia virus IgG was detected using an indirect immunofluorescence test (IFT). Lastly, MVA vector-specific immune responses were correlated to MERS-S-specific immune responses. Repeated vaccination with the vaccine candidate MVA-MERS-S induced MVA vector-specific cellular and humoral immune responses as presumed. Nevertheless, MERS-S-specific cellular and humoral immune responses were boosted after repeated immunizations with MVA-MERS-S even in the face of vector-immunity. There is no evidence for a negative influence of vaccine-induced MVA vector-specific immunity on the immunogenicity of the antigenic insert MERS-S. Further studies are required to determine the exact impact of MVA vector-specific immunity on vaccine immunogenicity. A detailed understanding of the development of vector immunity and its effect on immune responses to the antigenic insert may help to optimize future vector vaccine strategies.