BEIJING – There was encouraging news when vaccine developer Moderna Inc. announced this week that it has shipped the first vials of its mRNA vaccine against COVID-19 for a phase I trial in the U.S. The vaccine was created just 42 days after the genetic sequence of the COVID-19 virus was released.
That is record speed. Other vaccine developers are also working around the clock to respond to the epidemic. With previous work done for coronaviruses such as SARS and MERS, researchers can leverage existing knowledge and technology platforms to develop a vaccine for COVID-19 faster.
Inovio Pharmaceuticals Inc. is another forerunner in the vaccine race. CEO Joseph Kim told the forum attendees on Wednesday that the firm is preparing to start a U.S.-based phase I trial for its INO-4800 in early summer this year, and will open up a parallel study in China almost simultaneously.
“Our DNA medicines platform is very well-suited to responding to these modern-day emerging infectious diseases like COVID-19,” Kim said. “When the sequences were available on the internet, our scientists were able to construct our vaccine utilizing the sequence for the COVID-19 spike protein antigen in a few hours.”
The knowledge and technology accumulated from past coronavirus incidents have made this fight against COVID-19 less tricky.
“Because of SARS and MERS, there's a platform and there's data to work from,” said Gregory Poland, professor and director of Mayo Clinic Vaccine Research Group. “We understand the virus and we have the sequence of the virus. The crystal structure of the receptor has been resolved and identified as the ACE2 receptor.”
He said developing neutralizing antibodies is important, as previous SARS candidate vaccines were shown to be useful and protective against viral challenge. It is one of the approaches adopted by vaccine developers.
But to rapidly advance vaccine candidates into human trials, biotech scientists need to get preclinical studies done right, said Poland. Animal models still play a role in vaccine development.
“In our rush to develop a vaccine [for COVID-19], we have to remember that in preclinical studies, although mice and ferrets may be protected against viral challenges with these vaccines, there were also some early red flags,” Poland said. “There were occasions of a type II hypersensitivity pneumonitis that developed in some animal models.”
While speed is important, other factors such as quality and manufacturability cannot be overlooked, panelists reminded the research community on the forum.
“We need speed, but we still need quality. We don't want to introduce a second harm to people,” said Xuefeng Yu, CEO of Chinese vaccine developer Cansino Biologics Inc.
Xue said he believes animal models should be available before moving any vaccine candidates into human trials. The cautious scientist said it is critically important to check every step in order to make a vaccine that will eventually work without any concerns such as disease enhancement.
“Even though we have learned from MERS and SARS, [COVID-19] is still a new virus that behaves very differently, so we should really get some basic understanding,” Xue said.
Manufacturability was another concern among the panelists.
Xue said vaccine developers need to consider if their technology allows for mass production of their vaccine candidates in order to benefit the public. The view was shared by Mark Esser, vice president of microbial sciences at Astrazeneca plc.
“If you can't scale, it won't be a product,” Esser said. “You have to think about things like stability, chemistry manufacturing and controls reproducibility.”
That plays to the advantages of big pharma companies, which have the resources to scale up production once a vaccine candidate is ready for launch.
Johan Van Hoof, global area head of Janssen Vaccines and Prevention BV, said Janssen has invested a lot in the further development of its manufacturing platform that allows it to manufacture viral vector vaccines at extremely high cell density. The platform can produce about 9 million human doses. Once Janssen’s vaccine candidate for COVID-19 nears the end of the phase I trial, it can be put into production.
Is mRNA the future?
In a separate note on Moderna’s mRNA vaccine candidate, which will enter human trials for COVID-19 in six weeks, Mayo’s Poland said mRNA is a “very promising technology” that can send the genetic message for whatever proteins or polypeptides of interest that you want to develop immunity to. However, he is concerned about vaccines that are limited to one protein, “because you could certainly mutate through that,” he said.
Issues that need attention from a research point of view are, according to Poland, correlations of protection and more immunology, in order to really understand how mRNA, DNA or inactivated vaccines are acting and what kind of immunity they are producing. Antibody enhancement of the disease is another consideration.
Those questions will not be answered easily until these vaccines are used in a more widespread manner against the coronavirus, he said.