Nothing stands in ReiThera’s way except the bedeviling logistics of turning science into medicine.
Some of the pitfalls of that process have already shown up in the uneven and slower than expected global vaccine rollout. Even in places like Europe that, on paper, had secured multiple doses for every person, production shortfalls — and questions about the AstraZeneca vaccine’s efficacy for the elderly — have caused a panicked realization that the first wave of presumed solutions might not be enough.
But for vaccine manufacturers hoping to plug the gap, the path is at least as tricky as it was for the first-comers. Like its forerunners, ReiThera faces the challenge of quickly scaling up production. But it also faces a series of more novel obstacles, related to this particular point in the pandemic, when larger pharmaceutical companies have claimed dibs on crucial supplies and the existence of effective vaccines raises ethical questions about testing new ones.
For now, even as Italian politicians speak hopefully about having a domestically made vaccine by September, ReiThera acknowledges it is still trying to navigate long waiting lists for several basic components.
“There is a competition between the producers for the critical material,” said Stefano Colloca, the company’s chief technology officer.
The hurdles are big enough that some Italian scientists say it makes more sense to expand production of proven vaccines rather than investing resources to develop new ones. That idea got a high-profile boost last month when the French pharmaceutical company Sanofi, which had struggled in its own vaccine attempt, said it would instead produce 100 million doses of the vaccine made by its competitor, Pfizer.
Other scientists, though, argue that, in the long run, it makes more sense to have many vaccines rather than many doses of a few. The variety is crucial, they say, because it’s still far from clear which vaccines will respond well to new variants and which might afford longer protection or block transmission. Some vaccines might outdo others in safeguarding particular demographic groups.
“It’s a real palette. You have to think about it as an artist’s palette to paint this picture, and this picture is stopping the virus,” said Paul Duprex, director of the Center for Vaccine Research at the University of Pittsburgh. “That is why we need to have backups of backups of backups.”
The Pfizer-BioNTech and Moderna vaccines, the first two approved in Europe, use a new mRNA-based technology and have proved dazzlingly effective. But that technology makes them more expensive — and more difficult to store — than vector vaccines, which include those from AstraZeneca, Johnson & Johnson and ReiThera.
ReiThera executives say that if their vaccine falls short of expectations, they would in theory be able to produce AstraZeneca’s vaccine. But they call that a “Plan B.”
“We are still thinking that ours could be better,” Colloca said.
The company has a long list of issues to sort out first, however. It says it needs to hire and train 40 more people — a 35 percent expansion of its workforce. In November, it bought a 500-gallon vessel known as a bioreactor, which enables the chemical process for vaccine-making. But Colloca said there is now a months-long wait for even the single-use bags, which hold a starter kit of vaccine liquid, that are inserted into the vessel.
“We have some stockpiled,” Colloca said. “But not enough.”
ReiThera is even concerned about obtaining glass vials. Fearing a shortage, the company has searched for alternatives and is considering using a medical-grade pouch similar to an IV bag.
Then there’s the matter of ramping up production — and the possibility that manufacturing hiccups could cause shortfalls and delivery delays, as happened with AstraZeneca. Colloca said companies like his could learn from others’ struggles “only to an extent.”
“It’s not like AstraZeneca has said, ‘Here were our problems,’ ” Colloca said. “I can imagine. But I don’t know. They were not prepared to scale up. Most of the challenge is in scaling up.”
Italy’s government recently threw its support behind ReiThera’s venture, injecting 81 million euros into the company. Domenico Arcuri, who is both the commissioner leading Italy’s coronavirus response and the CEO of the Italian government investment arm, called ReiThera an “integral part of the Italian vaccination strategy and campaign.”
In a written statement to The Washington Post, Arcuri said he hoped doses could be available to the public “by the summer.”
In addition to supplying Italy — which is now getting doses from Pfizer, Moderna and AstraZeneca — ReiThera says it has also received inquiries from countries in South America and Eastern Europe. In those regions, a European-made vaccine would represent an alternative to options from Russia and China, which have targeted poorer countries, in part as a way to win influence and goodwill.
If there is enough interest from abroad, ReiThera says, it plans to collaborate with a Belgium-based commercial facility, Univercells, to expand production.
ReiThera’s vaccine candidate is one of 63 around the world in the midst of clinical trials, according to the World Health Organization. Before the pandemic, ReiThera was what Colloca called a “solid small company.” It was just a few years old, but its top scientists had years of experience making vaccines against emerging diseases, typically using modified adenoviruses from great apes.
The company said the results of its Phase 1 trial, completed this month, were encouraging: The vaccine appeared safe for both young and old, and it stimulated antibodies in more than 90 percent of volunteers.
Still, scientists caution that there are many kinds of antibodies, some that might powerfully fight the coronavirus and others that might not, and a Phase 1 trial does not provide enough information.
In normal situations, a company would eventually subject its candidate to a large-scale trial in which some volunteers would receive the vaccine and others would be given a placebo. But many medical experts say it is becoming murky whether a company can ethically inject people, especially the elderly, with nothing more than saline when efficacious vaccines are already available.
Antonella Folgori, ReiThera’s CEO, said there’s no doubt that placebo trials are the best way to test a vaccine, but she’s not sure ReiThera will be able to conduct one. She said she has obsessively been joining webinars, talking to others in the field, looking for signals on what governments are thinking. So far, Europe’s medical body has offered no rules.
There are conceivable alternatives, including the possibility of giving ReiThera’s vaccine to all volunteers, then comparing their antibody response to responses triggered by other, proven vaccines. But that comparison cannot be done based on the current level of scientific knowledge; more research must be done to determine which kind of immune response correlates with protection. That could be at least several months away, Folgori said, calling it a “fluid situation.”
“There’s still a chance that it doesn’t work out as we hope,” Colloca said. But, he said, “you cannot start this project if you’re not an optimist.”