7 New Insights about the Frontrunner U.S. Vaccine Candidate
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
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.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
After his grandmother’s dementia diagnosis, one man invented a snack to keep her healthy and hydrated.
On a visit to his grandmother’s nursing home in 2016, college student Lewis Hornby made a shocking discovery: Dehydration is a common (and dangerous) problem among seniors—especially those that are diagnosed with dementia.
Hornby’s grandmother, Pat, had always had difficulty keeping up her water intake as she got older, a common issue with seniors. As we age, our body composition changes, and we naturally hold less water than younger adults or children, so it’s easier to become dehydrated quickly if those fluids aren’t replenished. What’s more, our thirst signals diminish naturally as we age as well—meaning our body is not as good as it once was in letting us know that we need to rehydrate. This often creates a perfect storm that commonly leads to dehydration. In Pat’s case, her dehydration was so severe she nearly died.
When Lewis Hornby visited his grandmother at her nursing home afterward, he learned that dehydration especially affects people with dementia, as they often don’t feel thirst cues at all, or may not recognize how to use cups correctly. But while dementia patients often don’t remember to drink water, it seemed to Hornby that they had less problem remembering to eat, particularly candy.
Where people with dementia often forget to drink water, they're more likely to pick up a colorful snack, Hornby found. alzheimers.org.uk
Hornby wanted to create a solution for elderly people who struggled keeping their fluid intake up. He spent the next eighteen months researching and designing a solution and securing funding for his project. In 2019, Hornby won a sizable grant from the Alzheimer’s Society, a UK-based care and research charity for people with dementia and their caregivers. Together, through the charity’s Accelerator Program, they created a bite-sized, sugar-free, edible jelly drop that looked and tasted like candy. The candy, called Jelly Drops, contained 95% water and electrolytes—important minerals that are often lost during dehydration. The final product launched in 2020—and was an immediate success. The drops were able to provide extra hydration to the elderly, as well as help keep dementia patients safe, since dehydration commonly leads to confusion, hospitalization, and sometimes even death.
Not only did Jelly Drops quickly become a favorite snack among dementia patients in the UK, but they were able to provide an additional boost of hydration to hospital workers during the pandemic. In NHS coronavirus hospital wards, patients infected with the virus were regularly given Jelly Drops to keep their fluid levels normal—and staff members snacked on them as well, since long shifts and personal protective equipment (PPE) they were required to wear often left them feeling parched.
In April 2022, Jelly Drops launched in the United States. The company continues to donate 1% of its profits to help fund Alzheimer’s research.
Last week, researchers at the University of Oxford announced that they have received funding to create a brand new way of preventing ovarian cancer: A vaccine. The vaccine, known as OvarianVax, will teach the immune system to recognize and destroy mutated cells—one of the earliest indicators of ovarian cancer.
Understanding Ovarian Cancer
Despite advancements in medical research and treatment protocols over the last few decades, ovarian cancer still poses a significant threat to women’s health. In the United States alone, more than 12,0000 women die of ovarian cancer each year, and only about half of women diagnosed with ovarian cancer survive five or more years past diagnosis. Unlike cervical cancer, there is no routine screening for ovarian cancer, so it often goes undetected until it has reached advanced stages. Additionally, the primary symptoms of ovarian cancer—frequent urination, bloating, loss of appetite, and abdominal pain—can often be mistaken for other non-cancerous conditions, delaying treatment.
An American woman has roughly a one percent chance of developing ovarian cancer throughout her lifetime. However, these odds increase significantly if she has inherited mutations in the BRCA1 or BRCA2 genes. Women who carry these mutations face a 46% lifetime risk for ovarian and breast cancers.
An Unlikely Solution
To address this escalating health concern, the organization Cancer Research UK has invested £600,000 over the next three years in research aimed at creating a vaccine, which would destroy cancerous cells before they have a chance to develop any further.
Researchers at the University of Oxford are at the forefront of this initiative. With funding from Cancer Research UK, scientists will use tissue samples from the ovaries and fallopian tubes of patients currently battling ovarian cancer. Using these samples, University of Oxford scientists will create a vaccine to recognize certain proteins on the surface of ovarian cancer cells known as tumor-associated antigens. The vaccine will then train that person’s immune system to recognize the cancer markers and destroy them.
The next step
Once developed, the vaccine will first be tested in patients with the disease, to see if their ovarian tumors will shrink or disappear. Then, the vaccine will be tested in women with the BRCA1 or BRCA2 mutations as well as women in the general population without genetic mutations, to see whether the vaccine can prevent the cancer altogether.
While the vaccine still has “a long way to go,” according to Professor Ahmed Ahmed, Director of Oxford University’s ovarian cancer cell laboratory, he is “optimistic” about the results.
“We need better strategies to prevent ovarian cancer,” said Ahmed in a press release from the University of Oxford. “Currently, women with BRCA1/2 mutations are offered surgery which prevents cancer but robs them of the chance to have children afterward.
Teaching the immune system to recognize the very early signs of cancer is a tough challenge. But we now have highly sophisticated tools which give us real insights into how the immune system recognizes ovarian cancer. OvarianVax could offer the solution.”