Effect of Serial Passage on the Pathogenicity and Immunogenicity of Vaccinia Virus LC16m8 Strain

SIMPLE SUMMARY: There is great current interest in vaccines for use in the coronavirus disease 2019 (COVID-19) pandemic. Safety and efficacy are particularly important in vaccine development, and these depend on the properties of the vaccine and the response in the vaccinated person. Some vaccines produce a strong immune response but may also cause adverse events in certain individuals. It is particularly important to predict if a person may be vulnerable to these adverse events, and this is one of the purposes of the field of vaccinomics. In this review, we examine recent studies on vaccinia virus (VACV) vaccine, which is the key vaccine responsible for eradicating smallpox. In particular, we consider the different individual responses to this vaccine, and we discuss future research directions in this area. ABSTRACT: The phenotype of an attenuated live vaccine depends on gene mutation achieved by, for example, many passages in cultured cells. Viral clones with preferable phenotypes are selected and the causative genetic mutation(s) are later identified. LC16m8 is an example of a highly attenuated smallpox vaccine that was developed and licensed in Japan in the 1970s. LC16m8 was obtained by the passaging of Lister strain, with indicators of small plaque formation and temperature sensitivity as virus phenotypes. This strain can replicate in mammalian cells and provides robust cellular and humoral immunity, as well as long-term immune memory. Recent studies using proteome-wide antigen arrays have revealed that antibody production against LC16m8 and other VACVs differs largely among individuals. Moreover, associations between SNPs in immune-related genes and immune outcomes have been increasingly found. These results lead to predicting adverse events of a vaccine, which is a purpose of vaccinomics. Studies on VACV will continue to contribute to the understanding of host-pathogen interactions and to development of a vaccine for other infectious and non-infectious diseases. Here, we review studies of VACV, including our recent research on LC16m8, with a focus on the phenotype and genotype, and we discuss future research directions.