Earlier this year, biotech company Moderna broke world records for speed in vaccine development. Their researchers translated the genetic code of the coronavirus into a vaccine candidate in just 42 days.
We're about to expand our safety data in Phase II.
Phase I of the clinical trial started in Seattle on March 16th, with the already-iconic image of volunteer Jennifer Haller calmly receiving the very first dose.
Instead of traditional methods, this vaccine uses a new -- and so far unproven -- technology based on synthetic biology: It hijacks the software of life – messenger RNA – to deliver a copy of the virus's genetic sequence into cells, which, in theory, triggers the body to produce antibodies to fight off a coronavirus infection.
U.S. National Institute of Allergy and Infectious Diseases Director Anthony Fauci called the vaccine's preclinical data "impressive" and told National Geographic this week that a vaccine could be ready for general use as early as January.
The Phase I trial has dosed 45 healthy adults. Phase II trials are about to start, enrolling around 600 adults. Pivotal efficacy trials would follow soon thereafter, bankrolled in collaboration with the government office BARDA (Biomedical Advanced Research and Development Authority).
Today, the chief medical officer of Moderna, Tal Zaks, answered burning questions from the public in a webinar hosted by STAT. Here's an edited and condensed summary of his answers.
1) When will a vaccine become available?
We expect to have data in early summer about the antibody levels from our mRNA vaccine. At the same time, we can measure the antibody levels of people who have had the disease, and we should be able to measure the ability of those antibodies to prevent disease.
We will not yet know if the mRNA vaccine works to prevent disease, but we could soon talk about a potential for benefit. We don't yet know about risk. We're about to expand our safety data in Phase II.
In the summer, there is an expectation that we will be launching pivotal trials, in collaboration with government agencies that are helping fund the research. The trials would be launched with the vaccine vs. a placebo with the goal of establishing: How many cases can we show we prevented with the vaccine?
This is determined by two factors: How big is the trial? And what's the attack rate in the population we vaccinate? The challenge will be to vaccinate in the areas where the risk of infection is still high in the coming months, and we're able to vaccinate and demonstrate fewer infections compared to a placebo. If the disease is happening faster in a given area, you will be able to see an outcome faster. Potentially by the end of the year, we will have the data to say if the vaccine works.
Will that be enough for regulatory approval? The main question is: When will we cross the threshold for the anticipated benefit of a presumed vaccine to be worth the risk?
There is a distinction between approval for those who need it most, like the elderly. Their unmet need and risk/benefit is not the same as it is for younger adults.
My private opinion: I don't think it's a one-size-fits-all. It will be a more measured stance.
2) Can you speed up the testing process with challenge studies, where volunteers willingly get infected?
It's a great question and I applaud the people who ask it and I applaud those signing up to do it. I'm not sure I am a huge fan, for both practical and ethical reasons. The devil is in the details. A challenge study has to show us a vaccine can prevent not just infection but prevent disease. Otherwise, how do I know the dose in the challenge study is the right dose? If you take 100 young people, 90 of them will get mild or no disease. Ten may end up in hospital and one in the ICU.
Also, the timeline. Can it let you skip Phase II of large efficacy trial? The reality for us is that we are about to start Phase II anyway. It would be months before a challenge trial could be designed. And ethically: everybody agrees there is a risk that is not zero of having very serious disease. To justify the risk, we have to be sure the benefit is worth it - that it actually shrunk the timeline. To just give us another data point, I find it hard to accept.
This technology allows us to scale up manufacturing and production.
3) What was seen preclinically in the animal models with Moderna's mRNA vaccines?
We have taken vaccines using our technology against eight different viruses, including two flu strains. In every case, in the preclinical model, we showed we could prevent disease, and when we got to antibody levels, we got the data we wanted to see. In doses of 25-100 micrograms, that usually ends up being a sweet spot where we see an effect. It's a good place as to the expectation of what we will see in Phase I trials.
4) Why is Moderna pursuing an mRNA virus instead of a traditional inactivated virus or recombinant one? This is an untried technology.
First, speed matters in a pandemic. If you have tech that can move much quicker, that makes a difference. The reason we have broken world records is that we have invested time and effort to be ready. We're starting from a platform where it's all based on synthetic biology.
Second, it's fundamental biology - we do not need to make an elaborate vaccine or stick a new virus in an old virus, or try to make a neutralizing but not binding virus. Our technology is basically mimicking the virus. All life works on making proteins through RNA. We have a biological advantage by teaching the immune system to do the right thing.
Third, this technology allows us to scale up manufacturing and production. We as a company have always seen this ahead of us. We invested in our own manufacturing facility two years ago. We have already envisioned scale up on two dimensions. Lot size and vaccines. Vaccines is the easier piece of it. If everybody gets 100 micrograms, it's not a heck of a lot. Prior to COVID, our lead program was a CMV (Cytomegalovirus) vaccine. We had envisioned launching Phase III next year. We had been already well on the path to scale up when COVID-19 caught us by surprise. This would be millions and millions of doses, but the train tracks have been laid.
5) People tend to think of vaccines as an on-off switch -- you get a vaccine and you're protected. But efficacy can be low or high (like the flu vs. measles vaccines). How good is good enough here for protection, and could we need several doses?
Probably around 50-60 percent efficacy is good enough for preventing a significant amount of disease and decreasing the R0. We will aim higher, but it's hard to estimate what degree of efficacy to prepare for until we do the trial. (For comparison, the average flu vaccine efficacy is around 50 percent.)
We anticipate a prime boost. If our immune system has never seen a virus, you can show you're getting to a certain antibody level and then remind the immune system (with another dose). A prime boost is optimal.
My only two competitors are the virus and the clock.
6) How would mutations affect a vaccine?
Coronaviruses tend to mutate the least compared to other viruses but it's entirely possible that it mutates. The report this week about those projected mutations on the spike protein have not been predicted to alter the critical antibodies.
As we scale up manufacturing, the ability to plug in a new genetic sequence and get a new vaccine out there will be very rapid.
For flu vaccine, we don't prove efficacy every year. If we get to the same place with an mRNA vaccine, we will just change the sequence and come out with a new vaccine. The path to approval would be much faster if we leverage the totality of efficacy data like we do for flu.
7) Will there be more than one vaccine and how will they be made available?
I hope so, I don't know. The path to making these available will go through a public-private partnership. It's not your typical commercial way of deploying a vaccine. But my only two competitors are the virus and the clock. We need everybody to be successful.
On the morning of April 12, 1955, newsrooms across the United States inked headlines onto newsprint: the Salk Polio vaccine was "safe, effective, and potent." This was long-awaited news. Americans had limped through decades of fear, unaware of what caused polio or how to cure it, faced with the disease's terrifying, visible power to paralyze and kill, particularly children.
The announcement of the polio vaccine was celebrated with noisy jubilation: church bells rang, factory whistles sounded, people wept in the streets. Within weeks, mass inoculation began as the nation put its faith in a vaccine that would end polio.
Today, most of us are blissfully ignorant of child polio deaths, making it easier to believe that we have not personally benefited from the development of vaccines. According to Dr. Steven Pinker, cognitive psychologist and author of the bestselling book Enlightenment Now, we've become blasé to the gifts of science. "The default expectation is not that disease is part of life and science is a godsend, but that health is the default, and any disease is some outrage," he says.
The Rise and Fall of Public Trust<p>When the polio vaccine was released in 1955, "we were nearing an all-time high point in public trust," says Matt Baum, Harvard Kennedy School professor and lead author of <a href="http://www.kateto.net/covid19/COVID19%20CONSORTIUM%20REPORT%2013%20TRUST%20SEP%202020.pdf" target="_blank" rel="noopener noreferrer"><u>several</u></a> <a href="https://shorensteincenter.org/wp-content/uploads/2020/09/COVID19-CONSORTIUM-REPORT-14-MISINFO-SEP-2020.pdf" target="_blank" rel="noopener noreferrer"><u>reports</u></a> measuring public trust and vaccine confidence. Baum explains that the U.S. was experiencing a post-war boom following the Allied triumph in WWII, a popular Roosevelt presidency, and the rapid innovation that elevated the country to an international superpower.</p><p> The 1950s witnessed the emergence of nuclear technology, a space program, and unprecedented medical breakthroughs, adds Emily Brunson, Texas State University anthropologist and co-chair of the Working Group on Readying Populations for COVID-19 Vaccine. "Antibiotics were a game changer," she states. While before, people got sick with pneumonia for a month, suddenly they had access to pills that accelerated recovery. </p><p>During this period, science seemed to hold all the answers; people embraced the idea that we could "come to know the world with an absolute truth," Brunson explains. Doctors were portrayed as unquestioned gods, so Americans were primed to trust experts who told them the polio vaccine was safe. </p>
The Shift in How We Consume Information<p>In the 1950s, the media created an informational consensus. The fundamental ideas the public consumed about the state of the world were unified. "People argued about the best solutions, but didn't fundamentally disagree on the factual baseline," says Baum. Indeed, the messaging around the polio vaccine was centralized and consistent, led by President Roosevelt's successful <a href="https://files.eric.ed.gov/fulltext/EJ978264.pdf" target="_blank" rel="noopener noreferrer"><u>March of Dimes crusade</u></a>. People of lower socioeconomic status with limited access to this information were <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1551508/?page=3" target="_blank" rel="noopener noreferrer"><u>less likely to have confidence</u></a> in the vaccine, but most people consumed <a href="https://www.c-span.org/video/?506891-1/a-special-report-polio" target="_blank" rel="noopener noreferrer"><u>media that assured them</u></a> of the vaccine's safety and <a href="https://www.cbsnews.com/news/the-salk-polio-vaccine-greatest-public-health-experiment-in-history/" target="_blank" rel="noopener noreferrer"><u>mobilized them</u></a> to receive it. </p><p>Today, the information we consume is no longer centralized—in fact, just the opposite. "When you take that away, it's hard for people to know what to trust and what not to trust," Baum explains. We've witnessed an increase in polarization and the technology that makes it easier to give people what they want to hear, reinforcing the human tendencies to vilify the other side and reinforce our preexisting ideas. When information is engineered to further an agenda, each choice and risk calculation made while navigating the COVID-19 pandemic <a href="https://www.nytimes.com/2020/12/19/opinion/sunday/coronavirus-science.html?referringSource=articleShare" target="_blank" rel="noopener noreferrer"><u>is deeply politicized</u></a>. </p><p>This polarization maps onto a rise in socioeconomic inequality and economic uncertainty. These factors, associated with a sense of lost control, prime people to embrace misinformation, explains Baum, especially when the situation is difficult to comprehend. "The beauty of conspiratorial thinking is that it provides answers to all these questions," he says. Today's insidious fragmentation of news media accelerates the circulation of mis- and disinformation, reaching more people faster, regardless of veracity or motivation. In the case of vaccines, skepticism around their origin, safety, and motivation is intensified. </p><p>Alongside the rise in polarization, Pinker says "the emotional tone of the news has gone downward since the 1940s, and journalists consider it a professional responsibility to cover the negative." Relentless focus on everything that goes wrong further erodes public trust and paints a picture of the world getting worse. "Life saved is not a news story," says Pinker, but perhaps it should be, he continues. "If people were more aware of how much better life was generally, they might be more receptive to improvements that will continue to make life better. These improvements don't happen by themselves."</p>
The Future Depends on Vaccine Confidence<p>So far, the U.S. has been unable to mitigate the catastrophic effects of the pandemic through social distancing, testing, and contact tracing. President Trump has <a href="https://www.washingtonpost.com/politics/bob-woodward-rage-book-trump/2020/09/09/0368fe3c-efd2-11ea-b4bc-3a2098fc73d4_story.html" target="_blank" rel="noopener noreferrer"><u>downplayed the effects and threat of the virus</u></a>, <a href="https://www.washingtonpost.com/outlook/2020/07/14/cdc-directors-trump-politics/" target="_blank" rel="noopener noreferrer"><u>censored experts and scientists</u></a>, <a href="https://www.theatlantic.com/science/archive/2020/06/america-giving-up-on-pandemic/612796/" target="_blank" rel="noopener noreferrer"><u>given up on containing the spread</u></a>, and <a href="https://www.nytimes.com/2020/09/16/world/covid-coronavirus.html" target="_blank" rel="noopener noreferrer"><u>mobilized his base to protest masks</u></a>. The Trump Administration failed to devise a national plan, so our national plan has defaulted to hoping for the <a href="https://www.politico.com/news/2020/08/26/nation-of-miracles-pence-coronavirus-vaccine-rnc-402949" target="_blank" rel="noopener noreferrer"><u>"miracle" of a vaccine</u></a>. And they are "something of a miracle," Pinker says, describing vaccines as "the most benevolent invention in the history of our species." In record-breaking time, three vaccines have arrived. But their impact will be weakened unless we achieve mass vaccination. As Brunson notes, "The technology isn't the fix; it's people taking the technology."</p><p> Significant challenges remain, including facilitating widespread access and supporting on-the-ground efforts to allay concerns and build trust with <a href="https://www.newyorker.com/news/daily-comment/african-american-resistance-to-the-covid-19-vaccine-reflects-a-broader-problem" target="_blank" rel="noopener noreferrer"><u>specific populations with historic reasons for distrust</u></a>, says Brunson. Baum predicts continuing delays as well as deaths from other causes that will be linked to the vaccine. </p><p> Still, there's every reason for hope. The new administration "has its eyes wide open to these challenges. These are the kind of problems that are amenable to policy solutions if we have the will," Baum says. He forecasts widespread vaccination by late summer and a bounce back from the economic damage, a "Good News Story" that will bolster vaccine acceptance in the future. And Pinker reminds us that science, medicine, and public health have greatly extended our lives in the last few decades, a trend that can only continue if we're willing to roll up our sleeves. </p>
Imagine this scenario: you get an annoying cough and a bit of a fever. When you wake up the next morning you lose your sense of taste and smell. That sounds familiar, so you head to a doctor's office for a Covid test, which comes back positive.
Your next step? An anti-Covid nasal spray of course, a "trickster drug" that will clear the once-dangerous and deadly virus out of the body. The drug works by tricking the coronavirus with decoy receptors that appear to be just like those on the surface of our own cells. The virus latches onto the drug's molecules "thinking" it is breaking into human cells, but instead it flushes out of your system before it can cause any serious damage.
This may sounds like science fiction, but several research groups are already working on such trickster coronavirus drugs, with some candidates close to clinical trials and possibly even becoming available late this year. The teams began working on them when the pandemic arrived, and continued in lockdown.
Biochemist David Baker, pictured in his lab at the University of Washington.