A Comprehensive Report on Modified Vaccinia Ankara (MVA): From Attenuated Smallpox Vaccine to a Modern Vector Platform

1.0 Executive Summary

Modified Vaccinia Ankara (MVA) represents a landmark achievement in vaccinology, evolving from a highly attenuated, third-generation smallpox vaccine into a versatile and robust platform for developing vaccines against a range of infectious diseases and for novel cancer immunotherapies. Its defining characteristic is an exceptional safety profile, rooted in its inability to replicate in mammalian cells, which is a direct consequence of its unique development history involving over 500 serial passages in avian cells. This process induced significant genomic deletions, stripping the virus of key virulence and host-range factors while preserving its immunogenicity.

As a vaccine against orthopoxviruses, MVA-BN (marketed as JYNNEOS, IMVANEX, and IMVAMUNE) has demonstrated safety and immunogenicity in an extensive clinical trial program involving thousands of participants. Its critical role was validated during the 2022-2023 global mpox outbreak, where it became the primary prophylactic tool, particularly for high-risk and immunocompromised populations for whom older, replication-competent smallpox vaccines are contraindicated. Real-world data from this period confirmed its favorable safety profile and demonstrated vaccine effectiveness ranging from 66% to 89% for a complete two-dose course.