Modified Vaccinia Virus Ankara (MVA) based Vaccines – Immunostimulatory and Protective Capacity

Abstract

Modified vaccinia virus Ankara (MVA) is a highly attenuated and replication-deficient vaccinia virus (VACV) which serves as promising candidate replacement vaccine against smallpox. Moreover, genetically modified MVA viruses are investigated as vector vaccines against various infectious diseases and cancer. A long-standing observation is that non-replicating MVA vaccines are paradoxically immunogenic in comparison to immunizations with fully replication-competent VACV. Here, we present evidence from recent experiments supporting the notion that MVA has particular immunostimulatory properties. Immunizations in mouse models revealed the in vivo synthesis of type I IFN shortly after MVA vaccine administration, and the activation of dendritic cells by both TLR-dependent and TLR-independent pathways. In addition, rapid immigration of leukocytes into the lung of mice is triggered upon intranasal immunization with MVA and not with other VACV strains. Importantly, MVA infection efficiently induced the expression of several chemokines (CCL2, CCL3, CCL4, CXCL10), and we identified CCL2 as the main CC chemokine attracting monocytes after MVA infection in vitro and in vivo. We conclude that the failure of MVA to prevent early activation of type I interferon, chemokine expression, and early immigration of leukocytes contributes to its potential as a protective vaccine, and supports the suitability of MVA vaccines to serve for efficient prophylaxis against suddenly emerging infectious diseases.