📷 The Golden Goose Award
Journalist: Haleema Ahmed
Haleema Ahmed
Hello everyone and welcome back to SciSection. I’m Haleema, your journalist for this week, and today we are delighted to have Dr. Daniel Wrapp. Dr. Wrapp is a postdoctoral fellow at The Duke Human Vaccine Institute. He received his Ph.D. at Dartmouth College under the guidance of Dr. Jason McLellan and his work under the lab helped create the COVID-19 vaccine! Thank you for joining us.
Daniel Wrapp
Thank you for having me.
Haleema Ahmed
Before we get into your research, how did you get interested in vaccination research and your field as a whole? Was it a passion developed in undergrad? Before then?
Daniel Wrapp
When I was an undergrad, I knew I wanted to go to grad school because I wanted to do laboratory research. I was interested in microbiology and how that related to infectious disease. But to be perfectly honest, until I started doing this work, I didn't even really know that it was an option.
Haleema Ahmed
What are you working on now at the Duke Human Vaccine Institute after receiving your Ph.D.?
Daniel Wrapp
I'm trying to better understand why some people can mount an effective immune response against HIV infection. That's a long-standing question in research. We have access to a lot of patient samples here, which we hope can help us unravel that mystery a little bit.
Haleema Ahmed
HIV research has been a longstanding effort so that work is incredibly important. Moving into your work at the McLellan Lab may help to state the basics of coronaviruses and vaccines to better appreciate the research you’ve done. How does the virus infect us and what does the vaccine do to prevent infection?
Daniel Wrapp
I'll start sort of very broad and then narrow into what we ended up doing. There are two different flavors of viruses. There are naked viruses, which just have a capsid made out of protein surrounding their genetic information. Then there are envelope viruses, which have a lipid membrane that surrounds the genetic information. For envelope viruses, they need to fuse their lipid membrane with our host cells to replicate so that they can infect. In order to allow that membrane fusion event to occur, they have specialized proteins. That protein for the coronavirus is called a spike which binds to host cell receptors. In this case, the host cell receptor is called the angiotensin-converting enzyme 2. The virus and spike will bind and then a really dramatic conformational change will occur. What vaccines do is present the immune system with the spike so that you can raise antibodies against it. Once your body comes into contact with actual viruses, it's able to recognize that pre-fusion spike and prevent it from associating with the receptor and causing membrane fusion. If those antibodies are raised, which are capable of neutralizing the virus, you are going to be protected from infection.
Haleema Ahmed
Your lab had experience working with both the MERS and SARS coronaviruses. How did this information particularly allow your team to rapidly get into COVID research and accomplish what typically takes months or even years to do?
Daniel Wrapp
That's a really good question. Something that a lot of people might not appreciate is that coronaviruses refer to a whole family of different viruses, which as you said, include MERS SARS-1, SARS-2. So by studying these viruses that emerged before SARS, our team, particularly a postdoc named Dr. Nianshuang Wang, and my boss, Dr. Jason McLellan, were able to determine a set of mutations that stabilized spike proteins from all these different coronaviruses in the prefusion conformation, which makes it sort of an ideal vaccine candidate. Because these prefusion stabilizing mutations were broadly applicable to multiple different Coronavirus spikes, as soon as the genome sequence of SARS-Cov-2 was released, we were able to translate these mutations into the new virus and rapidly develop an ideal vaccine candidate.
Haleema Ahmed
A large part of the work that you guys did was in developing this 3D atomic model. Why was this model so essential in the development of the vaccine and what was it like working with your team to accomplish that?
Daniel Wrapp
At the time, it was really exciting. We didn't know that it was going to cause a global pandemic at that time, but we did know that it was going to be a broad interest because it was a newly emerging Coronavirus and it had the potential to help people who were already becoming infected. What we did was determine the 3D atomic structure of SARS-Cov-2 and its associated spike protein which helped us to put it into the context of previously determined prefusion structures. How this virus is similar to other coronaviruses that we know more information about and how it is different were questions the atomic model can help us answer. We can use that information to design smarter therapeutics and smarter vaccine candidates,
Haleema Ahmed
A really cool piece of technology used in the research is called the Cryogenic Electron Microscope. How did this technology support your research and how do you see it being further applied?
Daniel Wrapp
In order to determine the structures in these proteins, we have to be able to see them, which is a problem because they are smaller than the wavelength of visible light, which means they're quite literally invisible. So rather than using light microscopes to try to observe these tiny little particles, what we use are electron microscopes. In particular, the one that we use is called a cryo-electron microscope, because the sample has to be frozen to prevent radiation damage. As you said, that allows us to view these tiny objects embedded in incredibly thin layers of ice. We can then calculate three-dimensional volumes to explain those particles that we see embedded in ice. This technology has been a huge advance in the field of what I do in structure determination. As the hardware and software to both image these particles, and then make sense of what you're imaging continues to advance, I think the field is going to keep sort of jumping ahead, and now
Haleema Ahmed
Moving into present-day vaccination efforts, now that we have more deadly and contagious variants, how is the effectiveness of the vaccine then impacted? This is concerning the research your team did in modeling the vaccine and in turn, that research being used to develop the vaccine?
Daniel Wrapp
That model we calculated has been really useful in tracking where on the spike these mutations are occurring. A lot of these mutations occur in what's called the receptor-binding domain. They circumvent the antibody response to make the virus less susceptible to neutralization. Fortunately, vaccines still seem to be effective against the variants that are cropping up. But every time the virus replicates, there is potential for the creation of a new variant that is more resistant to the current vaccines. So it's really important to stop replication whenever possible.
Haleema Ahmed
On that note, thank you so much Dr. Wrapp for speaking to us today about the groundbreaking work you did at the McLellan Lab in developing the COVID-19 vaccine. Follow him on Twitter @LabWrapp to keep up with his incredible research. Thank you for joining us!