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The success of a second vaccine against Covid-19 means the world is a big step closer to curbing the coronavirus pandemic.

Moderna, joined by U.S. government scientists, announced Monday that their mRNA vaccine candidate was 94.5% effective in preventing Covid-19, the disease caused by the novel coronavirus, according to an interim analysis of a 30,000-patient clinical trial. The news comes exactly one week after Pfizer and BioNTech said their respective Covid-19 vaccine candidate, also created using mRNA technology, was more than 90% effective in its own 60,000-patient clinical trial. 

Here’s what we know — and still need to learn — about the two most advanced Covid-19 vaccines and how they might reshape the pandemic that has killed 1.3 million people worldwide and infected at least 54.5 million. 

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Are the two vaccines equally effective?

It’s too early to tell for certain, but the overall efficacy of the vaccines appears to be similar, based on the data disclosed to date. This isn’t altogether surprising, since the Moderna and the Pfizer/BioNTech vaccine candidates are both based on the same kind of technology

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Based on data disclosed Monday, the Moderna vaccine appears to have been protective in important subsets of participants — the elderly and people from communities of color, the latter of which make up 37% of the volunteers in Moderna’s trial. 

Moderna also released data about the number of participants who developed severe Covid-19. There were 11 cases of severe disease, all of them in the placebo group. The elderly often respond less robustly to vaccines and are more vulnerable to having severe cases of Covid-19, if infected.

The clinical trial conducted by Pfizer and BioNTech included the same subpopulations of participants, but specific results have not been disclosed.

We don’t know how effective these vaccines are in the long-term.

Some immunizations provide protection against a pathogen for decades (think the measles vaccine). It’s thought that the benefits of a Covid-19 vaccine — no matter the manufacturer — won’t last nearly as long. But researchers won’t know how long until the immunity offered by these vaccines begins to wear off. This will be something scientists keep an eye on in the months to come.

“We do not know at this point what the durability of protection will be,” Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, said on a call with reporters Monday.

How long vaccine-derived protection lasts has implications not only for manufacturing and how frequently people might be required to get boosters, but also for the ongoing risk of transmission of SARS-CoV-2. 

There are other unanswered questions about these vaccines as well. For one, the trials were designed primarily to look at the impact on symptomatic Covid-19. But experts will also want to see if the vaccine candidates can block infections entirely, or if they’re just making people less sick. Another: If people can still contract SARS-2 after getting vaccinated, are they less infectious to other people? 

The safety profile of the vaccines is encouraging, so far.

So far, both vaccines appear to be generally tolerable — but by no means painless. In its announcement Monday, Moderna said it observed a few short-lived severe side effects in volunteers, including fatigue, muscle pain, and headache. None required hospitalization. For its part, Pfizer said last week that its independent data monitors reported no serious safety concerns. In an earlier update from its Phase 1 clinical trial, Pfizer’s vaccine led to mild or moderate fever and pain at the site of injection, side effects that resolved over time, the company said.

But the most important safety data won’t come until patients have been followed for months and even years. Pfizer and Moderna have promised to collect and disclose that information in time.

What does this mean for the other vaccines in development?

While both the Moderna and the Pfizer/BioNTech vaccines are based on mRNA technology, the other frontrunners — from AstraZeneca and Johnson & Johnson — use different approaches. (Other companies, including Sanofi, are at work on mRNA vaccines, but their candidates are not as far along in the development process.)

But all the top candidates are targeting the virus’ spike protein, which the pathogen uses to infect cells. The results from the Pfizer and Moderna trials give hope that other vaccine candidates could be effective as well, given that they’re all going after the same bull’s-eye. 

“Today’s announcement provides further confirmation that spike-directed vaccines can provide a protective immune response,” said Richard Hatchett, the CEO of the Coalition for Epidemic Preparedness Innovations, known as CEPI. 

What does this mean for mRNA?

Outside of its implications for the global pandemic, the tandem success of Moderna and Pfizer’s vaccines is a massive affirmation of the promise of mRNA, a medical technology that has advanced in fits and starts for three decades.

At the start of 2020, SARS-2 was a virus that had never been studied, or even known. Less than a year later, two companies have developed what appears to be an effective vaccine for it. That suggests mRNA technology can be used to rapidly design and deploy vaccines for other pathogens. In Moderna’s case, it bodes well for in-development vaccines for Zika virus and cytomegalovirus, and it supports the company’s long-term plan to get into the business of manufacturing flu vaccines each year. For Pfizer’s partner BioNTech, which is developing vaccines for cancer, HIV, and influenza, it’s similarly encouraging.

Scientists can now design genetic material called mRNA to help us build immunity to certain viruses, including SARS-CoV-2, the coronavirus that causes Covid-19. Find out how mRNA vaccines work in this video. Hyacinth Empinado/STAT

At the same time, vaccines have always been the lowest hanging fruit in the minds of mRNA researchers. The baseline promise of mRNA is that it can compel cells in the body to manufacture a specific protein, treating or preventing disease in the process. But developing mRNA medicines has always been a delicate balance: Scientists have to administer enough of the synthetic substance to ensure protein production, but not too much so as to avoid a dangerous immune reaction. 

Vaccines, which require only one or two doses of mRNA, are the most logical application of the technology. The bigger — and more lucrative — use for mRNA would be therapeutics for the scores of diseases that can be treated by making certain proteins in the body. That would require routine and lifelong administrations of mRNA, something neither Moderna nor BioNTech is yet to crack in a large clinical trial.

When can I get a vaccine? 

Both Moderna and Pfizer have promised to file for emergency use authorizations in the coming weeks. If the FDA grants them, as it’s widely expected to do before the end of the year, the companies will ship doses to the federal government, which is in charge of allocating the limited supply to front-line workers and people at an elevated risk of severe Covid-19.

For everyone else, neither vaccine is likely to be available until spring at the earliest, in large part because of logistics. (By that time, Pfizer and Moderna are also likely to have generated enough supporting data to justify full FDA approvals.) Pfizer and Moderna expect to produce just 70 million doses of their vaccines by the end of 2020, enough for only 35 million people around the globe. In 2021, the companies could have as many as 2.3 billion doses between them, but in a pandemic-ravaged world of 7.5 billion people, that’s not going to be enough to satisfy demand. Unless more Covid-19 vaccines prove to work in the coming months, the world will be rationing doses well into next year.

Further complicating matters is the issue of storage. Pfizer is capable of manufacturing more doses than Moderna, but its vaccine must be shipped and stored at ultra-cold temperatures, which could make it difficult to deploy in parts of the world that lack specialized freezers. By contrast, Moderna said its vaccine can be safely stored in a conventional refrigerator. That sets up a short-term situation in which Pfizer’s vaccine is the most bountiful but Moderna’s is the most convenient, which will require some deft maneuvering on the part of global health agencies.

Vaccines are important, but only if people get them.

Public health experts are quick to tell you: Even the world’s best vaccine won’t do much unless people are willing to get it. 

This has been a particular concern with Covid-19 vaccines, as polls show that a substantial portion of Americans — whether because of how fast the process has moved or because of concerns that the vaccine review process would become politicized — said they would not get a Covid-19 vaccine when it became available. Skepticism about Covid-19 vaccines was even higher among people of color, who have experienced historic and ongoing mistreatment and discrimination in health care, and who are suffering from a disproportionate impact of the pandemic in the United States. 

As vaccines start to roll out, the supply will be so limited that they’ll be used for frontline workers or people more vulnerable to Covid-19. But eventually, immunizations will be more widely available, and the majority of Americans will need to get vaccinated if the pandemic is going to draw to a close. Health authorities planning for the allocation and distribution of Covid-19 vaccines have been taking this into account as they’ve charted out their campaigns. 

There’s another piece of good news in just how effective the Pfizer and Moderna vaccines appear to be. Experts believe — and polling data supports — that reluctance to get vaccinated may abate in some quarters if the vaccines work well. The public has been more or less warned these vaccines might be flu vax redux — and at least half the public doesn’t think flu vax is worth getting. A highly efficacious vaccine bodes well for uptake. 

Helen Branswell and Matthew Herper contributed reporting.

  • There is no long term data on safety or efficacy. This is an mRNA vaccine using a process that has never been tested before in humans. Some people who have been infected have long term effects of the virus, and my concern is that can happen with the vaccine–as the mRNA of the virus replicates in the host after vaccination. So without having a clue about duration, or efficacy–I find the data sketchy since there hasn’t been a full study released–this is going to be released. And the public is going to be under pressure to get vaccinated, and I’ve seen all sorts of threats looming around, like not being able to attend school, or get on a plane, or go to a concert, etc without the vaccine. A vaccine which has no data to support it except 2-3 months of testing in a small group of patients–not large enough for the more rare side effects to emerge.

    Plus exposure–participants were observing precautions, as indicated by two comments below. So the real numbers are unknown, how effective it would be in “real life.” People may not have been infected because they are observing protocols, working from home, limiting contact. The number of cases in either group is way too small to draw any conclusions–and again, it could be that the people who were infected were more careless in placebo vs vaccine. The only way to really tell, given that people are purposely avoiding infection, is a challenge study. Then you know for sure. At any rate, I will happily get at the end of the line, as I wouldn’t go anywhere near that vaccine until we have 2-3 years real world data.

  • Reality check
    A vast portion of the world, that is not the US and partially western Europe, has been moving forward regardless mRNA vaccines, by using old fashion (but likely more effective) vaccines.

  • Thank you, Annie and Becca, for answering my question and explaining more on these trials. I feel this information should be mentioned in the news. A CNN medical correspondent said to “go out and live your lives” but it wasn’t clear to me what that really meant. I assumed you were all told to follow masks, etc. protocols but I didn’t know for sure. It makes a difference to me knowing that. Thank you!

  • When you look at the number of people that received placebos and got infected, the overall results look very underwhelming. In either the Pfizer or Moderna trials, the vaccine doesn’t greatly reduce your odds of being infected. They made it look good by comparing the two counts for infections. Perhaps, the trial needs to run much longer in order to get the number of infections that would be statistically significant. I have no interest in a vaccine that reduces my odds from 0.6 percent to 0.1 percent.

    • What are you talking about? The control group had 90 cases of SYMPTOMATIC COVID-19 vs 5 in the vaccinated cohort. That is a 95% reduction in relative risk not an 83% reduction as your maths would imply.

      More importantly the control group had 12 severe cases of COVID-19 vs. ZERO in the vaccinated cohort. I.e. A 100% reduction in relative risk.

      You need to remember these trials on average have only been active for a couple months.

      The ‘risk’ of catching COVID-19 at ANY TIME is not 0.6%. It is close to 100% if you are immunologically naiive and the pandemic continues its course (which it will in the U.S. absent a co-ordinated health response and/or a vaccine rollout).

      The risk of developing symptomatic COVID-19 will be lower than 100% of course. Amongst the general population it may only be c70% (MUCH higher in aged cohorts and MUCH lower in young cohorts) with the balance being asymptomatic infections amongst people able to mount a robust T-cell response.

      Nevertheless you can’t look at a 30,000 person trial and allege it is useless because ONLY 95 people got symptomatic COVID-19 over the last couple months:
      – First the majority of the trial period has been during late summer and early autumn. Wait until winter to see how quickly the trial enrollees get infected;
      – Second enrollees in clinical trials are ON AVERAGE FAR more concerned about their health. I.e. Their relative chance of catching COVID-19 AT ALL is much lower in the short term than the population average;
      – Third the trial used a saline placebo that had ZERO side-effects. This means most participants can guess whether they got vaccinated or received the placebo. I.e. Trial enrollees in the active arm would have been FAR less cautious than trial enrollees in the control arm. In that context the results are terrific.
      – Fourth the vaccine has ALREADY demonstrated VERY ROBUST statistical significance. The chances of those results (90 vs. 5) in a randomised double blind trial occuring by chance is 1 in 10,000 (hence why the P value is 0.0001)!

      The results will only become more robust as more of the enrollees get infected. However it should be noted that the FDA has agreed to the trial ending at ONLY 151 enrollees becoming infected with symptomatic COVID-19 out of the 30,000 enrollees.

      I.e. An interim readout at 95 is already has 63% of the statistical power of the full trial result.

  • I have been trying to find out what the participants did as far as using masks, social distancing. When told after getting vaccinated with vaccine or the placebo to go out and live your life were they wearing masks, etc. or living life as they were before Covid? Can anyone answer that question for me or tell me how to find that information? Thank!

    • I am a trial participant. I have absolutely worn a mask and taken precautions. We were not told to go live our lives like pre-covid.

    • I am also a trial participant. Just like everyone else, we also had to follow local mandates as far as wearing masks and social distancing. When I have been outside I have not worn a mask but when I have entered businesses that required them I had to wear a mask just like everyone else. The rules were not changed for those of us who participated in the trials.

  • Bad reporting. There is no track record for mRNA vaccines, and the dangers that exist for patients with autoimmune diseases or plasma cell malignancies are very real possibilities that no one has any data on. The effect upon these large populations are unknown and can’t be estimated until the vaccine has been in use for years. The public is essentially going to be an experimental cohort. Changing someone’s genome that has an immune disorder is a monumental risk that has zero back data.

    • Thanks for this comment – I have one of those chronic conditions that could be autoimmune (no one knows about most of these mysterious tick-borne/psychosomatic/nutritional/auto-immune/genetic/viral/whatever syndromes) and will be tracking the data closely and probably delaying taking the vaccine.

    • I am not quite sure what your last sentence is referencing. The 2 vaccines that we are hearing about now are both mRNA vaccines, not DNA vaccines. As far as I could find out neither the Moderna nor BionTech vaccines have replicating mRNA. They have been altered to stabilize the mRNA for 2 weeks before breaking down during which time they will be used in translation to have our ribosomes assemble a COVID-19 spike protein to stimulate our immune response. Since it is mRNA and not DNA it can’t alter our genome. My concern was whether it was replicating and how long it would last with the modifications to stabilize it. Clearly one doesn’t want to overstimulate the immune response so how much antigen is produced for how long is a concern.

    • Well while you hang around for a couple years worth of data I’m going to be enjoying the protective effect of the vaccine.

      Think I’d rather take a 1 in 100,000+ chance of a very rare side effect than the 1 in 10 or 20 so chance of hospitalisation and > 1 in 1000 chance of death…

    • Yes! I have Multiple Sclerosis I am NOT getting this vaccine come hell or high water! I am not risking my life for something that has NOT been throughly tested and was rushed through! Most of these main stream news channels hype and fear monger about cases and deaths to flat out lie!! I believe this whole covid is being used for the gr8t re- set anyways!..so it can’t be good! It’s all about control NOT health! And I stand by it!!!

  • Why not use Pfizer facilities to produce Moderna vaccine which is far better in many respects? Just pay them more. It is money well spent.

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