著者

赤畑 渉

雑誌

日本薬学会第141年会(広島)

巻号頁・発行日

2021-02-01

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We have developed a vaccine candidate for COVID-19 that is based on a self-amplifying RNA (replicon) vaccine vector expressing the receptor-binding domain (RBD) of SARS CoV-2 with modifications to optimize structure, presentation, and immunogenicity. Immunization with this replicon vector provides high expression levels of antigens and induction of strong immune responses using vectors that are safe and well tolerated. The high expression is due to the efficient intracellular replication of the RNA and amplified expression that also provides a significant dose-sparing effect. The dose-sparing effect is especially important during pandemics where large numbers of doses must be manufactured quickly. The focus on the RBD sequences for this vaccine was driven by the observation that the majority of virus neutralizing antibodies are directed at this region, and also by a concern that non-neutralizing antibodies directed at other domains on the spike (S) protein could contribute to immune-mediated pathologies as has been documented for other viruses in this family. Intramuscular immunization of mice with this replicon induces robust antibody responses as monitored by ELISA, inhibition of RBD binding to the ACE-2 receptor and SARS CoV-2 virus neutralization. We plan to manufacture this vaccine and enter clinical trials. This system represents a platform technology that could be used to address additional emerging viruses.