These first results, published Tuesday in the New England Journal of Medicine, showed that the vaccine worked to trigger an immune response with mild side effects - fatigue, chills, headache, muscle pain, pain at the injection site - becoming the first An American vaccine candidate will publish his results in a peer-reviewed medical journal
The vaccine is expected to start a large phase 3 trial later this month - the last step in the trial before regulators wonder if the vaccine should be available.
Moderna noted in a press release on Tuesday that, if all goes well in future studies, "society remains on track to be able to deliver around 500 million doses a year, and possibly up to 1 billion doses per year, starting in 2021. "
"We thought the immune responses looked promising, but we don't know if the levels we are observing would actually protect against infection. It's really hard to know until you do the actual efficacy test ", she said. "So we are preparing the ground for the trial that will provide these answers."
Moderna plans to start the company's largest study to date on its Covid-19 vaccine candidate, mRNA-1237, on July 27, according to details released separately on Tuesday. He is expected to be the first in the U.S. to begin phase 3 trials.
For now, the new study "quickly provides information that could be used to determine which dose to go forward with phase 2 and phase 3 trials. This is a critically important decision to make and so having this information available so soon after the start of the vaccine trial is quite remarkable, "said Jackson.
A phase 1 study typically studies a small number of people and focuses on the safety of a vaccine and triggers an immune response.
In phase 2, the clinical study is expanded and the vaccine is given to people who have characteristics - such as age and physical health - similar to those for whom the new vaccine is intended, according to the Centers for Disease Control and Prevention of the United States. . In phase 3, the vaccine is administered to thousands of people and tested for its effectiveness and again for its safety.
"We want to know if the vaccine is safe and effective"
The phase 1 study included 45 healthy adults, ages 18 to 55, who received two vaccinations of the mRNA-1237 vaccine candidate 28 days apart. Some of the volunteers signed up for the trial at Kaiser Permanente in Seattle and others at Emory University in Atlanta.
The volunteers were separated into groups where they received the vaccine at a dose of 25, 100 or 250 micrograms. They received their first vaccination between March 16 and April 14.
"The first dose strengthens the immune system, it's called priming," said Jackson. "Whereas when you re-administer the same thing, there is a booster response. There is an augmented response. So we didn't think that a single vaccination would be enough to get the level of response we wanted see."
The researchers found "no safety concerns limiting the trials" after the volunteers received their two doses of vaccine, but there were mild to moderate side effects, such as pain at the injection site, and there was more as the dose of the vaccine increased.
After the first vaccination, adverse events were reported by five participants in the 25 microgram group, 10 in the 100 microgram group and eight in the 250 microgram group. Then, after the second vaccination, such events occurred in seven of the 13 participants in the 25 microgram group, all 15 in the 100 microgram group and the 14 in the 250 microgram group, three of these participants reporting "one or more several serious events ", according to the study.
The most frequently reported systemic adverse events after the second vaccination at a dose of 100 micrograms were fatigue, among 80%; chills, among 80%; headache, among 60%; and myalgia or muscle pain, among 53%; all were transient and of mild or moderate intensity, as reported in the Moderna press release.
The study data also showed that the vaccine elicits an antibody response. Antibodies are the proteins the body makes to fight infection.
Specifically, all of the participants developed neutralizing antibodies to the virus at levels similar to those seen in people who have naturally recovered from Covid-19, according to the study. Neutralizing antibodies bind to the virus, preventing it from attacking human cells.
Researchers measured two types of immune responses, said Jackson.
"These two types of responses support each other. We know that antibodies are produced and there seems to be a function after vaccination that blocks the ability of the virus to enter cells. It therefore neutralizes the activity of the virus ", she explained. said.
But more research is needed.
"What do we really want to know? We want to know if the vaccine is safe and effective, that's what we want to know," said Dr. Paul Offit, a member of the NIH group that establishes a framework for vaccine studies in the United States, which did not participate in the new study.
With the study, "we know it's safe for 45 people, which isn't going to be the 20 million people or 200 million people who are going to get it here in the United States," said Offit, who is also director of the Vaccine Education Center and an attending physician in the Infectious Diseases Division of the Children's Hospital of Philadelphia.
"So we know it doesn't have a very common side effect problem, that's what we know," he said. "So we don't know anything about the efficacy, that's what we really want to know. Is this vaccine going to work? The only way to know is by doing a so-called phase 3 trial."
Moderna plans to launch large trial of US Covid-19 vaccine in late July
The results of the phase 1 study can help guide the aspect of the phase 3 study.
"These phase 1 data demonstrate that vaccination with mRNA-1273 induces a robust immune response at all dose levels and clearly supports the choice of 100 μg in a priming and booster regimen as the optimal dose for the Phase 3 study, "Dr. Tal Zaks, chief medical officer of Moderna, said Tuesday in the company's press release.
"We are looking forward to starting our phase 3 mRNA-1273 study to demonstrate the ability of our vaccine to significantly reduce the risk of COVID-19 disease," he said.
For the phase 3 study, the researchers plan to enroll 30,000 adult participants, including people whose location or circumstances put them at high risk of infection. One group will be injected with 100 micrograms of vaccine on day 1 and again on day 29. A second group will be injected with two doses of a placebo for comparison.
Fourteen days after participants receive their second dose, the researchers will examine whether they are developing Covid-19. Participants will be followed for two years after receiving their second dose.
The study will be conducted at 87 sites in the United States.
Moderna's vaccine candidate is one of 23 clinical trials worldwide, according to the World Health Organization.
Overall, "the safety and immunogenicity data from this preliminary report are promising and support the continued development of this vaccine. However, we must keep in mind the complexity of vaccine development and the work that remains to be done before Covid-19 vaccines are widely available. available, "wrote Dr. Penny Heaton, executive director of the Bill and Melinda Gates Foundation on Tuesday, in an editorial accompanying the New England Journal of Medicine phase 1 study.
"Accelerating the development of Covid-19 vaccine candidates beyond phase 1 depends on continuous parallel monitoring of activities and full resources. The world has now seen the compression of 6 years of work in 6 months," wrote Heaton . "Can the multiverse vaccine start over, leading to the reality of a safe and effective Covid-19 vaccine for the most vulnerable of the next six?"
