MERS, which struck South Korea in a 2015 outbreak, was caused by a coronavirus — the same family of viruses that is responsible for COVID-19 (disease: COVID-19, virus: SARS-CoV2). A Korean research team has developed a new vaccine platform using RNA-based adjuvants for the MERS coronavirus (MERS-CoV). The research team successfully conducted an experiment on nonhuman primates. It is expected that the new vaccine platform will soon be applicable to the development of a COVID-19 vaccine, an urgent global health priority.

The Korea Institute of Science and Technology (KIST)  recently released the results of the joint research on the RNA-based vaccine platform for MERS-CoV, conducted by a research team led by Dr. Keum Gyo-chang and Dr. Bang Eun-kyoung from the KIST's Center for Neuro-Medicine and a research team led by Professor Nam Jae-Hwan from the Catholic University of Korea (CUK, President Won Jong-chul). The vaccine platform uses RNA as an immunostimulatory agent known as an adjuvant and consists of compounds that maintain the stability of the RNA and spike protein (a surface protein that the MERS coronavirus uses to bind to a cell receptor) that the virus uses to invade the host cell. The new vaccine platform is expected to be used in the development of a vaccine for the COVID-19 virus, which is also a type of coronavirus.

Recently, many protein-based vaccines have been developed as they are regarded as having a high level of safety. However, protein-based vaccines induce a weak immune response in antibody-producing cells. This requires the use of a highly stable adjuvant for a more balanced immune response.

Dr. Keum Gyo-Chang (right) and Dr. Bang Eun-Kyoung (left) from KIST’s Center for Neuro-Medicine are discussing the efficacy of RNA stabilizer containing zinc complex. (Credit: Korea Institute of Science and Technology)

The joint research team mixed the RNA of the cricket paralysis virus (virus that paralyzes and kills crickets), an adjuvant developed by the CUK research team, and an RNA stabilizer containing zinc complex, developed by the KIST research team. A vaccine was created using the mixture, along with the spike protein of the MERS-CoV, and administered to a group of mice. After just one inoculation, the vaccine was shown to have adequate protective efficacy (100% protective efficacy against lethal doses of the virus). The MERS-CoV infection was also suppressed through the induction of high neutralizing antibodies (PRNT80 titer > 1:2,560) when the same vaccine was administered to macaque monkeys, which are nonhuman primates. RNA adjuvant and stabilizer mixed together can be applied to most vaccine types, including protein-based vaccines and inactivated vaccines, meaning that they have a wide range of potential uses.

The joint research team was provided the coronavirus spike protein by Dr. Song Man-ki's research team at the International Vaccine Institute. For the research, Professor Lee Sang-myeong's research team at Chonbuk National University measured the amount of antibodies (neutralizing-antibody values) and conducted a virus challenge experiment, and Dr. Hong Jung-joo's research team at the National Primate Research Center, which is part of the Korea Research Institute of Bioscience and Biotechnology, investigated the immunity of nonhuman primates such as monkeys.

Dr. Keum Gyo-chang from KIST says, “This RNA adjuvant formulated protein vaccine, which has shown efficacy against the MERS virus, has the advantage of rapid application to the development of a vaccine for COVID-19, which is caused by the same type of virus that causes MERS.” Professor Nam Jae-Hwan from CUK further explains, “The nucleic acid (DNA or RNA)-based vaccines that have recently been reported, have not previously been produced as vaccine products and have not gone through large-scale clinical trials. In contrast, the protein based vaccine is mainly used vaccine platform. In this study, we added RNA as adjuvant to protein vaccine whose safety has already been proven. We expect that this new vaccine platform will enable the development of a safe vaccine.”

Currently, the CUK research team is developing a COVID-19 vaccine and a vaccine for “severe fever with thrombocytopenia syndrome” (with research funds provided by Samkwang Labtree), using the vaccine platform. The research team has formed a consortium with SK Bioscience, to manage the development of a COVID-19 vaccine.

The research, backed by the Ministry of Health and Welfare , was conducted as part of the Vaccine Development to Respond to the Infectious Disease Crisis Project. The research was also backed by the Ministry of Science and ICT  and was conducted as an Institutional Research Program of the Korea Institute of Science and Technology and as a Next Generation New Medicine Foundation Technology Development Project. An article explaining the results of the research was recently accepted in the chemistry journal Angewandte Chemie.