TOKYO >> Wataru Akahata, CEO of VLP Therapeutics Japan LLC, thinks he can provide a solution to the challenge of securing COVID-19 vaccines for billions of people. His solution: the development of a second-generation messenger RNA (mRNA) vaccine that requires only a fraction of the dose of those currently available.
The biotech startup will file an application for a clinical trial in June, with the initial stage expected to start in the summer. Unlike the mRNA vaccines made by U.S.-based Pfizer Inc. and Moderna Inc., VLP’s proprietary “replicon” RNA will self-amplify inside the body before producing the antigen proteins that induce immune responses against the coronavirus.
The key benefit of self-replicating vaccines is their efficiency. They would require just a fraction of the dosage of conventional vaccines to trigger a strong immune response. Scientists have calculated that these vaccines could involve a dosage of one-tenth or less of the mRNA COVID-19 vaccines that are currently in use.
Self-replacing vaccines might enable production of unparalleled speed, some scientists say. Second-generation mRNA COVID-19 vaccines are now undergoing clinical trials around the world.
“We’re aiming for a significant reduction in dosage, so we expect to vastly speed up production compared with other vaccine platforms,” Akahata said. “We are also hoping that the lower dosage will reduce side effects in people.”
If an initial clinical trial confirms safety, the company is considering follow-up trials in Japan. But the country’s low number of COVID-19 cases makes securing trial candidates a challenge, and the company is likely to seek conditional approval instead.
“We will focus all our efforts on Japan, as there’s a heightened need for domestic vaccines,” he said. The company aims to deliver the vaccine next year.
He said the vaccine provides protection against the more contagious variants from the U.K., South Africa and India and that updating it to address new mutations could be done “very quickly.”
VLP’s PROJECT has been awarded a grant of $90 million by the Japan Agency for Medical Research and Development.
Akahata said his company’s mRNA vaccine is unique in that it encodes only the signature part of the spike protein that the immune system recognizes and attacks, and this allows it to kill the coronavirus more efficiently. He says that once self-amplified, the mRNA is designed to produce proteins that would be immediately attacked by the immune system. “Scientifically, it would be impossible for the mRNA to continue self-replicating for long.”
But some experts have expressed concerns about the unfettered self-replication of RNA.
“I’m worried that the mRNA, which is mass-produced by self-replication, would give a strong stimulus to humans’ natural immunity,” which might lead to unintended side reactions, said Tetsuo Nakayama, director of the Japanese Society of Clinical Virology.
Globally, several companies have been developing self-replicating mRNA vaccines. San Diego-based Arcturus Therapeutics Holdings Inc. has conducted a randomized clinical trial involving 580 participants of its single-dose vaccine in the U.S. and Singapore, and is preparing to begin a large-scale trial. A clinical trial also began in Japan in May, with Elixirgen Therapeutics Inc. conducting a trial of 60 participants.
VLP’s early vaccines might require freezing, Akahata said, but the company aims to follow up with a freeze-dried vaccine, which would address storage, handling and deliveries to developing countries.
“This technology has so much room for improvement, so I’d like to nurture it with great care,” he said.