Moderna’s Covid-19 vaccine led patients to produce antibodies that can neutralize the novel coronavirus that causes the disease, though it caused minor side effects in many patients, according to the first published data from an early-stage trial of the experimental shot.
The results were published Tuesday in the New England Journal of Medicine. Moderna had previously released some results in a press release, but many experts said they were not sufficient to draw many conclusions. Even now, many are withholding judgment.
“It certainly is a good beginning,” said Betty Diamond, director at the Feinstein Institutes for Medical Research, who was not involved in the trial. “There are certainly lots of things we don’t know yet right now.”
The study, which was run by the National Institutes of Health, showed that volunteers who received the vaccine made more neutralizing antibodies than have been seen in most patients who have recovered from Covid-19. But a second injection, four weeks after the first, was required before the vaccine produced a dramatic immune response.
“The hallmark of a vaccine is one that can actually mimic natural infection and induce the kind of response that you would get with natural infection. And it looks like, at least in this limited, small number of individuals, that is exactly what’s happening,” said Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, the NIH branch that conducted the trial. “The data really look quite good,” he added. “There were no serious adverse events.”
The data roughly mirror the results from a similar vaccine being produced by Pfizer and BioNTech, which were released July 1.
Moderna posted a listing on clinicaltrials.gov, a government registry, that says it will start a Phase 3 study in 30,000 patients on July 27. Pfizer and BioNTech said they plan to start their own large study by the end of the month. There are 23 vaccines in human clinical trials against the virus, SARS-CoV-2, according to the World Health Organization, with more set to begin testing soon.
In a statement, Moderna CEO Stéphane Bancel called the data “encouraging,” saying they “represent an important step forward” in the development of the vaccine, called mRNA-1273. “We are committed to advancing the clinical development of mRNA-1273 as quickly and safely as possible while investing to scale up manufacturing so that we can help address this global health emergency,” Bancel said.
One big question is whether producing antibodies predicts protection against infection — and how much protection. Another is whether the antibodies will last.
“We don’t know how much [antibody] we need to be protected, so we can’t say” all the participants “achieved a protective level,” Kathryn Edwards, scientific director of the Vanderbilt Vaccine Research Program, said in an email to STAT. “What we can say is that they made antibody that neutralized the virus, which is good.”
The study enrolled 45 healthy volunteers ages 18 to 55, testing three dose levels of Moderna’s vaccine. The trial participants were split roughly 50-50 between men and women. The population was 89% white, 13% Hispanic, 4% Black, 2% Asian, and 2% Native American. More results are expected to be reported later for older patients, who often mount a weaker immune response.
Volunteers got a shot in the arm on day 1 followed by a booster shot four weeks later. At the 100-microgram dose, the one Moderna is advancing into larger trials, all 15 patients experienced side effects, including fatigue, chills, headache, muscle pain, and pain at the site of injection. All side effects were considered mild or moderate.
A higher, 250-microgram dose led to more serious reactions and has been set aside. Although no side effects were severe — meaning that they required hospitalization — they were unpleasant, as was made clear when one volunteer in the study, Ian Haydon, went public with his experience taking the 250-microgram dose.
Researchers and drug companies have been racing with unprecedented speed to create a vaccine against the coronavirus. Moderna began its Phase 1 trial just 66 days after scientists first decoded the genome of SARS-CoV-2.
“It’s amazing just how fast we’ve gotten to this point,” Penny Heaton, CEO of the Bill and Melinda Gates Research Institute in Cambridge, Mass., said in an interview. “It’s like six years of work has been compressed into six months.”
That very speed is a reason for caution, said Paul Offit, chief of the division of infectious diseases at the Children’s Hospital of Philadelphia. He advised companies to be humble. He noted that he had worked on rotavirus vaccines for 25 years, and still the first attempt at one turned out to have a side effect that sent researchers back to the drawing board.
Already, he said, SARS-CoV-2 has done things experts never would have expected, he said. It spreads in hot weather. It causes deadly blood clots. It rarely makes children sick, but sometimes causes a surprising immune disorder. “I can promise you that over the next two years, we’ll learn a lot of things that we wish we’d known now that we are going to learn as we move forward,” Offit said.
Researchers measured the efficacy of Moderna’s vaccine in multiple ways, all of which showed higher average antibody levels than were seen in patients who had recovered from Covid-19. It took time for antibody levels to rise. Only after the booster shot did volunteers compare favorably with recovered patients.
In an editorial in NEJM, Heaton noted that it needs to be confirmed that measurements of such antibodies predict efficacy. “They are the best tools available,” she wrote, “and are supported by findings in nonhuman primates.”
At the 100-microgram dose, patients had neutralizing antibody levels, measured in what are called geometric mean titers, of 231.8 at day 57, compared to 109.2 in patients who recovered from Covid-19.
Experts said that given the multiple types of tests, it is impossible to compare vaccines based on laboratory results between different vaccines. For its vaccine, Pfizer had said that neutralizing antibody levels were 267 at 28 days, but they were 94 (a lower level than Moderna reported) in recovered patients, apparently using a different test. Pfizer has not disclosed data beyond 28 days.
Asked to compare the Moderna and Pfizer vaccine data, Fauci said, “I don’t think you could say anything about one being better than the other. They both induce good responses. Let’s see what happens in the real world.”
Several researchers said that seeing the results increased their hope not so much in Moderna’s vaccine, but in arriving at one or more vaccines that will help reduce the impact of the virus.
“I am cautiously optimistic, based on the data that we’ve seen so far, that amongst the several different vaccine platforms that are being tested, there seem to be encouraging Phase 1 data to suggest that at least one of them is going to work,” said Francis Collins, director of the National Institutes of Health. “And maybe several of them.”
But he warned that such science is not predictable. “Hence the word cautiously is attached to the word optimistic in this situation,” Collins said.
This story has been updated with comments from Anthony Fauci.
Helen Branswell contributed reporting.
Those who refuse to wear masks would certainly be opposed to receiving a vaccine.
For people residing in poor setting such as in the Developing World, the use of of effective masks , maintenance of distancing and washing of hands more frequently by everyone in the outside of their house are yet the best bet to mount a resistance to the deadly virus.This message has not percolated the world over.
And they need not receive one if they don’t want it, at least for time being, for unlike diphtheria, polio, and measles the new Covid vaccines won’t have had enough clinical experience accrued behind them to warrant making them prerequisite to school attendance. That’s something legislatures can think about in ten years or so.
But you’re right. Anti-mask and anti-vaxx seem almost the same crew in action, and unlike a shot that might prove unexpectedly dangerous, masks are safe, cheap, and perfectly suitable for public health to mandate in crowded public settings. We should wash our hands, keep our distance and use our masks in rich countries, too, as these are the only available infection control tools right now. Covid is wiping the US out on account of its obstinate refusal to put health over politics.
We never hear that the scientist, manufacturors or thier famlies being used or volunteering for the testing.
Maybe they have to much info on the dangers. ???
Let me Google that for you: https://en.wikipedia.org/wiki/Self-experimentation_in_medicine#Infectious_diseases_and_vaccines
In the absence of conventional test-proven anti-corona vacc weaponry, here is my own & my partner’s self-testing positive health record over the past decade: WE have been without fevers, sore throats, gastric problems etc., ever since we have been self-medicating with our own, home-made probiotic KomboChai plus KomCHI. In our opinion, this success validates medical tests to be followed on a big scale. Feedback most welcome via Youthevity.com
Sounds promising.
I do not think that evidence of a response to RNA means much concerning the immune response to an intact virus swimming towards its target with its RNA inside a protein vesicle covered with sugars
Lets Bill and Melinda try it first on their kids!!!
…first on their own, then on their kids…
In study on the 27, hoping for good things.
Interesting that the immune response reduced between days 43 and 57. Perhaps this is normal for vaccines. But I wonder how frequently we’ll need to be vaccinated. Perhaps two injections every four months, i.e. 6x/year ?
Fine, working on a prevention when a raging spread is underway and we have no immediate treatment. Please bear with me and follow this analogy, even if non-biotech. Here goes… A suburban housing development of 100 houses has an invasion of Deer Mice in their basements. 85 out of 100 homes have mice, 15 don’t. NOW, how do we solve this? Do we study the Deer Mouse and sequence it’s genome and find out WHY it likes basements? or do we study the 15 houses with NO MICE? YES the obvious is to study the 15 with NO MICE and find out why. OF course, these 15 homeowners have a cat in the basement. So, to stop the “Pandemic” of mice, we give every homeowner a cat! Then when we have things “under Control” we can study the mouse and discover it can squeeze through 1/2 inch crack. We then “Vaccine” the basements of all homes with some expanding insulation foam. AND we live happily ever after. NOW, get the point? BIG PHARMA needs to STUDY the ASYMPTOMATIC VS the “Hospitalized” and find out what factors are present that block the COVID19 receptors. Then this factor becomes a treatment and prevention when introduced to the public. JUST DO IT!
I don’t think it’s quite that simplistic. First, who’s to say someone isn’t looking into that? Secondly, It’s possible that asymptomatic carriers have a genetic variation that inhibits the cytokine storm that is causing the hospitalizations. And you can’t just up and change everyone’s genomes. It’s also very possible that asymptomatic carriers simply were exposed to a much lower viral load. They just didn’t have as much of the virus in them as those who were hospitalized. And that’s exactly what masking, social distance, and hand washing is for — to limit viral load exposure. So in that respect we’ve already been doing what you suggest. Also, why should we only pursue one path or another? Why not both at the same time by different groups of people? In your analogy, it would work like this: the ASPCA gives (or sells) a basement cat to everyone who wants one (and is not allergic to them) while at the same time, a group of contractors work to figure out the best way to seal the 1/2 inch crevices that would prevent the mice from eventually eating through the sealant. That’s pretty much what’s going on.
Interesting that liver enzymes weren’t reported since one would think liver toxicity is a risk of a lipid nanoparticle delivery system. Would have been helpful to see the comparable T-cell response in convalescent patients for comparison.
In a typical phase 1 study of a novel vaccine, at least one test for liver toxicity would in fact be suggested to manufacturers and results would constitute part of the report of study results. The fact that we (the public) don’t know the results does not mean that a test was not done. If liver function tests were part of the protocol, FDA reviewers have full access to any such data. I am not sure why you think the Moderna vaccine is particularly likely to damage the liver, but I do agree that at least one test for liver toxicity should have been done, just as a matter of course, and may very well have been done. (I am an MD/scientist with 40 years of experience as a virologist at NIH and FDA.)