[초청강연] Development of attenuated Smallpox vaccine: KVAC103

Development of attenuated Smallpox vaccine: KVAC103

Sang-Gu Yeo, DVM, PhD.
Smallpox, a disease caused by variola virus, is one of the most dangerous diseases and had killed numerous
people before it was eradicated in 1980. However, smallpox has been re-emerged as the most threatening bio-
terrorism agent, the governments of many countries, as well as Republic of Korea, have stockpiled the smallpox
vaccine to prepare the potential bioterrorism threats. Because the first- and second- generation smallpox
vaccines were controversial with severe adverse reactions, new demands of safe smallpox vaccine have been
raised and some attenuated smallpox vaccines have been developed. In that, we have developed cell-culture
based highly attenuated third-generation smallpox vaccine candidate KVAC103 strain by 103 serial passages of
Lancy-Vaxina strain derived from the Lister in Vero cells. Several clones were selected considering shape, size,
and growth rate in mammalian cell and the clones were inoculated intracerebrally in suckling mice to test
neurovirulence by observing survival. Protective immune responses in adult mice were examined by measuring
the level of neutralization antibody and IFN-γ expression. Among several clones, clone 7 was considered as best
alternative candidate since there was no mortality in suckling mice against a lethal challenge. In addition,
enhanced neutralizing antibody and T-cell mediated IFN-γ production were observed in clone 7-immunized
mice. Clone7 was named “KVAC103” and used for skin toxicity test and full-genome analysis. KVAC103-
inoculated rabbits showed reduced skin lesions comparing to Lister strain, Lancy-Vaxina. Whole genome
analysis of KVAC103 revealed two major deleted regions that might contribute to reduced virulence of
KVAC103 comparing to Lister strain. Phylogenetic inference supported the close relationship with Lister strain.
Collectively, our data demonstrate that KVAC103 holds promise for use as a third-generation smallpox vaccine
strain due to enhanced safety and efficacy.