Scientist optimistic for vaccine by end of year
Researchers around the world are working frantically to create a vaccine for COVID-19. More than 150 vaccines are in some phase of development, with 23 now in human trials.
This week brought a spot of good news from one of the frontrunners: According to a study published in the New England Journal of Medicine, in a “Phase 2” trial, Moderna’s vaccine led 45 patients, ages 18-55, to produce antibodies able to neutralize the virus — and in doing so caused only minor side effects, such as headaches and fatigue.
That vaccine is based in part on the work of Jason McLellan , an associate professor of bioscience at the University of Texas. He spoke with us from his office.
Lots of us are holding our breaths waiting for a COVID-19 vaccine that would let us resume our normal lives. But we know that vaccines usually take 10 years to develop. Is it possible to get one faster?
A:
I’m optimistic about the current vaccine development for SARS-CoV-2/ COVID-19. I think we are likely to have one or more approved for use by the end of this year. That would be historically fast: The fastest vaccine ever developed took four years.
Wow. Let’s back up to December, when the new coronavirus appeared. How did your lab get involved so fast? Did you receive some sort of Bat Signal?
A:
Information was circulating on Twitter. A lot of us scientists all follow each other, so at the end of December 2019, we were aware that these pneumonia outbreaks were occurring in Wuhan. That suggested either an influenza virus or a coronavirus.
Early in January 2020, it was confirmed that it was a coronavirus — a beta coronavirus, similar to the first SARS. I was snowboarding in Park City, Utah, when I got a call from Dr. Barney Graham at the National Institute of Health’s vaccine research center. I’ve worked with him since 2009; we researched spike proteins on other coronaviruses.
Barney said, “It looks like it’s a beta coronavirus. We want to race on this; try and get a vaccine out quickly. Do you want to collaborate?”
I immediately texted my lab: “We’re gonna get going on this.”
On Jan. 10, Chinese researchers made the sequence of the SARS-CoV-2 genome available online. So that weekend, we started designing exactly what we wanted the vaccine antigen to look like.
Barney got in contact with Moderna. And then from there, it’s been a sprint.
So what is an antigen? This thing you designed?
A:
An antigen is a portion of the virus, or even the whole virus, that’s injected as part of a vaccine, so that our immune systems learn to recognize the virus.
There are different ways to make a vaccine; we’re seeing that now. One is, you use the entire virus. It can’t be the full infectious virus because then you’d just be infecting people. So you attenuate it in some way — inactivate it or kill it. Several of those wholevirus vaccines are being developed. But in China, the data on those haven’t looked so good.
The other way is to use portions of the virus that our immune system can learn to recognize. If you’ve seen pictures of the coronavirus, you’ve seen these large proteins on the surface sticking out — the spikes. That is what our immune system recognizes. When people are infected with coronaviruses, we make antibodies against the spike protein.
For the virus to infect us, the spike protein is critical.
It has two functions. The spike binds to receptors on the surface of our cells, and that attaches the virus to our cells.
Then, once bound, the spike undergoes this major rearrangement, kind of like a Transformer, and it fuses the viral membrane with our host cell’s membrane — and that fusion of the two membranes allows the viral genome to enter the cell. So then the cell is infected.
We want the vaccine to lead to antibodies that can stop those two processes — that can prevent attachment and that prevent the membrane-fusion process. So we know to use the spike or a portion of the spike as our vaccine antigen. That’s what most of the vaccines are doing.
Phase One: Those are the very first trials in human beings? To be sure the vaccine doesn’t outright kill people?
A:
Yeah. Phase One is in human beings. Moderna’s is done, and the information on it just came online this week in the New England Journal of Medicine.
Phase Ones are generally done with tens of people — 30 or 40 people. You just want to make sure that it’s safe, that you’re not getting a lot of adverse events. It generally involves dose escalation. The first couple people will get a relatively small dose, then you wait a week or two to see what happens. If that looks okay, then the next set of people get injected with maybe five times as much, etc.
Phase One can also give you some idea of the vaccine’s efficacy. You can draw blood and look to see: Did the people make antibodies that can neutralize the coronavirus?
We hear a lot about the immune system over-responding to COVID — about cytokine storms that come late in a serious infection. Could that be a problem with vaccines? Would we have to worry that in some people, you might get an over-response?
A:
Probably not. I think a lot of that is being exposed to really high viral loads. The virus has many different genes that it uses to interfere with our immune response. You really wouldn’t get that with any of these mRNA or DNA or sub-unit vaccines, where you’re just injecting one protein. We’re just raising the antibody response against that one thing.
But if that’s an issue, we would see such things in the larger clinical trials.
Is that why we have enormous clinical trials? To look for unusual responses?
A:
Exactly. If there’s a side effect that occurs in 10 percent of people, in a 50-person trial you’d expect to see that in around five people. But what if there is an adverse event that only occurred in one out of 1000 people? To see that two or three times, you’d need a clinical trial that has several thousand people.
So we scale up. Phase Two is in the hundreds of people, and Phase Three is in the thousands or tens of thousands.
Phase Three is not just about safety. It’s also about efficacy, about how well the vaccine works. One group is going to receive a placebo, and one is going to receive the actual vaccine, and then you can compare outcomes — hospitalizations, duration of hospitalization, deaths, things like that. Hopefully the group that received the vaccine fares better than the group that received the placebo.
That’s the testing phase that Moderna is about to enter.
So once testing shows that we have a vaccine that’s safe and effective, how long does it take to produce and distribute it? How long until it’s in my arm?
A:
Going by what Moderna and others have claimed, I think they would start trying to make tens of millions of doses in the fall, then hopefully tens of millions of doses per month, and then scale it up into the hundred million doses per month.
One of the benefits of having more than one vaccine that works is that you’d have multiple companies that might be able to make 10 million doses per month, and that would allow more people to get immunized.
A lot of these plants, they’re being scaled up now. They’re starting to make a vaccine on the assumption that it’s going to work. They’re not waiting to see whether it works before ramping up.
That’s what Operation Warp Speed is doing: providing the money upfront so we can start large-scale manufacturing, so that we’ll be ready right away if a vaccine works.
But we’d love to have multiple options. It’d be great to have viable vaccines in the different modalities. DNA, mRNA, viral vector and protein-based: those are all manufactured differently, so you’re not putting all your eggs in one basket. If there’s some supply issue with one, you’d still have two or three others.
What else do you want Houstonians to know? What should we be watching as we wait for a vaccine?
A: The Phase Three trial is pivotal. That’s really what we’re really aiming for. So hopefully there’ll be some interim results. It’d be great to know by September if the vaccines are working.
Most people think you’ll need a prime. So you’d get vaccinated, and then you’d come back two or four weeks later for the boost, and then a few weeks after that, you’d probably be maximally protected. In the trials they’ll be monitoring to see how long it is before people that are vaccinated just once get infected. That’ll determine whether you need yearly injections or every other year.
Right now, with COVID, I think the main thing is just trying to keep the cases down. Obviously in Texas we’re just exploding with COVID cases from opening up too early. We just need everybody to social distance, be responsible, wear masks. Try to keep the numbers down. Buy time for the vaccine to be developed and distributed.
This interview has been edited for length and clarity.