Moderna Vaccine Looks Safe, May Need Two Doses. Now To Test It In 30,000 People

Moderna's coronavirus vaccine appears safe and stimulates the production of key antibodies that might prevent COVID-19, according to preliminary results that the Cambridge biotech published Tuesday.

Those findings alone are not enough to say the vaccine will work for sure, says Dr. Christopher Gill, an infectious disease researcher at Boston University who was not involved with the research.

“You need bigger studies for that,” he says.

Moderna plans to begin a clinical trial with 30,000 participants at the end of this month to determine how effective the vaccine is.

The preliminary study, published in The New England Journal of Medicine, presented evidence from 45 participants, each of whom received two injections of the vaccine at varying strengths. Most experienced mild to moderate side effects including pain at the injection site, headaches or nausea. Only those who received the strongest dose of the vaccine had more serious reactions, like a high fever and fainting.

Overall, though, Gill says the study suggests the vaccine is safe.

“It didn’t strike me, given the data, that this is a particularly reactive vaccine. It seemed quite well tolerated, in fact,” he says. “I didn’t see any major tolerability issues and no safety issues raised in terms of serious adverse events.”

The researchers also found high concentrations in the participants’ blood of antibodies that might protect against the coronavirus. Gill says that finding, along with the safety data in the study, provide ample evidence that Moderna was correct to forge ahead with their vaccine. If the biotech is successful in the subsequent phase two and three clinical trials, Gill says, that would be the key to bringing the vaccine to market.

“This would be a huge deal for vaccinology, and a huge deal for Moderna,” he says. “A vaccine that could save the world and salvage the economy. I think they’d be very pleased with themselves.”

Here are some key takeaways about Moderna’s vaccine:

The vaccine is built on a new technology that’s never been approved.

The vaccine contains messenger RNA or mRNA, genetic code that instructs the cell to manufacture a specific protein. In this case, the vaccine contains RNA code for the coronavirus’ spike protein – a structure on the outside of the virus that allows it to enter and infect human cells.

When injected, "those genetic instructions are taken up by a human cell, and the cell will dutifully create those spike proteins. Then the spike proteins will generate an immune response,” Gill says.

If everything goes well, that immune response will create antibodies that will protect people from COVID-19. The FDA has yet to approve a vaccine using this technology, so Moderna’s would be the first if the coronavirus vaccine reaches the market.

Researchers still aren’t sure if the vaccine will work based on the new evidence, but the initial results are promising for a two-dose vaccine.

The scientists studying Moderna’s vaccine are looking for a specific type of antibody called “neutralizing antibodies” that work by blocking the virus’ ability to enter and infect human cells.

“Imagine the [spike protein] is like a teapot,” Gill says. “If you’re really trying to figure out how to neutralize the function of a teapot, the only antibodies sticking to it that matter are the ones that stick to the spout and plug the hole.”

In this case, the researchers were looking specifically for antibodies that could stick to the “spout” of the spike protein and prevent it from binding to human cells. They found that after the participants received two injections of the vaccine, they had even higher concentrations of these types of antibodies in their blood than people who had recovered from COVID-19.

“The argument is that the vaccine might, in theory, do a slightly better job even than the native human immune response without running the risk of dying from COVID-19,” Gill says. But one dose may not be enough to elicit the needed level of neutralizing antibodies, “so this is probably going to be a two-series vaccine, which is not the end of the world. But it certainly would be far more convenient for it to be a single dose.”

While some people experienced negative side effects, results from the phase one trial show the vaccine is safe.

The phase one trial gave participants injections of 25, 100 or 250 micrograms of the vaccine. Higher doses meant more side effects. While the majority of participants suffered some side effects, Gill says that’s not a concern.

“The overall rates of adverse reactions they’re reporting is not remarkable. It’s higher than you would expect to see with a seasonal influenza vaccine, but similar to what you might see with vaccines like the measles or MMR vaccine where the virus actually replicates inside you,” Gill says. “It's certainly not one that would be a major concern.”

The phase three clinical trial is set to start in late July and last months. If successful, it will provide the final evidence the company needs to move the vaccine to the market.

Moderna hasn’t announced where the trials will be taking place, but the company’s corporate affairs chief Ray Jordan says it will likely be conducted in parts of the country where COVID-19 is spreading more rapidly. Half of the 30,000 participants will receive two 100-microgram injections of the vaccine, one month apart, and the other half will get a placebo.

After a few months, Jordan says researchers will check to see how many in each group actually contracted the coronavirus and became sick.

The company says it is on track to produce 500 million to 1 billion doses of the vaccine per year, beginning in 2021.