Q&A: KGI research professor Larry Grill talks COVID-19 vaccines and variants

A hand with a white glove holds a syringe over a metal vial with a vaccine.
TSL sat down with KGI professor Larry Grill to discuss COVID-19 vaccines and variants. (Courtesy: Lisa Ferdinando via WikiMedia Commons)

As more infectious COVID-19 variants have emerged around the world, experts are saying the United States must adapt to a changed pandemic playing field. TSL sat down with Larry Grill, dean of research and research professor at Keck Graduate Institute, to discuss COVID-19 vaccines, variants and his work on low-cost vaccines for developing countries.

The interview has been lightly edited and condensed for clarity.

TSL: How does the COVID-19 vaccine work? What is the purpose of the second dose?

LG: The current COVID-19 vaccines that have been approved in the [United States] are both messenger RNA types. One was synthetically made in a lab, so the nucleotides for the messenger RNA are slightly different from ours. A replicase enzyme is added, which will actually make multiple copies in it once it gets there to make it last longer [in the body]. The good part about both of [the vaccines] is they last for several days, which is what you really want, but both [vaccines’ protection] disappear within a short time. That’s why you need to come in with the booster, because you need to do a second job on it to try and make it successful. 

The other two types that are coming down, AstraZeneca and the Johnson & Johnson, are what we call live recombinant viral vaccines. That means that they’ve taken a weakened virus that does not cause disease in humans, and genetically changed it so it’s now displaying the same spike protein as SARS-CoV-2.

So what you’re getting is a virus that looks like COVID-19 but is totally ineffective and unable to cause an infection. But what it is able to do is train your immune system on that spike protein so that you build up antibodies — immunity — against the live recombinant vaccine. Then, because it’s a super weakened form, your body beats it up and learns how to fight it. When you get the real source code to the virus, your immune system is able to knock it out very quickly and very easily. 

In the messenger RNA vaccines, which I talked about earlier, that’s kind of a synthetic infection. They’re not infections. They make a spike protein, and your immune system notices there’s a foreign protein being produced by these cells. 

It mounts an immune response against these cells and also against the spike protein, which is now being put into your body. So within a matter of days, your immune system has been able to get rid of all the cells that were displaying this protein. But your immune system is now trained to go after [COVID-19], should it ever infect you.

TSL: Is it possible to develop low-cost COVID-19 vaccines for developing countries?

LG: Absolutely. We have already been working on low-cost vaccines for developing countries, like in Botswana. We were primarily working on a viral disease that is common in herds belonging to smallholder farmers in Africa. In April, we put several of our researchers on making the spike protein and using the same exact low-cost system to make a COVID-19 vaccine. We now put our COVID-19 vaccine in small animals, and we’ve gotten an immune response that we hope will be robust enough to provide immunity, but we’re still in the middle of those tests. 

The concept of it is that we actually use a plant virus. It’s easy to make … but they’re only dangerous to plants. We found out that if you inject the virus into humans, your immune system will make antibodies against that virus, and basically have total immunity. 

What we’ve done is take this plant virus and we change the outside surface to look like a pathogen that would infect a human or an animal. So for instance, the one we’re making right now … has protein sequences that are the same as the spike protein that’s bound on the SARS code to the virus. We’ve done small animal tests right now, and the mice immune system sees this virus and goes after the virus [and] starts making antibodies and building up immunity against that. And what it’s really building up immunity against is that [SARS] spike protein. 

TSL: What is the most important element in the fight against COVID-19?

LG: Rapid response. We’ve never been good at responding to a pandemic. For example, with Ebola — that’s been going on since 1976, our response to it has been poor. And in 1994, we still did not have any way of treating it. So that outbreak killed a lot more people [and had] several outbreaks. But finally, [in 2019], we came out with our first vaccine against Ebola. And it’s this new technology, which is the live recombinant, which is similar to AstraZeneca and Johnson & Johnson [vaccines].

We just had a new outbreak of Ebola, and now we finally have a way to actually surround it [and] to vaccinate the people and contain it much more easily than we have before. But outbreaks and pandemics are going to happen again and again. 

What we need to do is build up rapid response. And so what I’ve been showing — and, of course, now Moderna and Pfizer has been showing — is that we can react more quickly. This is basically a test of our system. With our [lab’s] three workers only, we’ve been able to do a rapid response and actually have a candidate that would actually have eight different possibilities.

I think the one good thing coming out of this pandemic, if you can say that anything that comes out of it is good … is we’re actually learning more about how to have a rapid response and effectively knock it down. 

I’ve already gotten my first dose of the Pfizer vaccine and I get my second dose [a] week from Saturday. I’m going to feel really relieved that my immune system has now been trained to recognize that spike protein, so if I ever get the source code to my immune system will know what to do. 

TSL: Why are there so many COVID-19 variants?

LG: Well, that’s actually just straight virology. Many of the RNA viruses mutate fairly rapidly. So if you consider the flu virus: It mutates every year so we know we have to prepare [another vaccine] for the following year. The SARS-CoV-2 virus is also an RNA virus, and it mutates just as rapidly as anything else. It’s going to try to keep mutating so it can spread more effectively than it has before. And it’s doing a pretty good job. 

We’ve seen [in the lab] that they are not necessarily that different … but [they spread] more rapidly. So far, there’s a lot of data that suggests that many of the vaccines will actually still be effective against these variants. 

But should one come up [such that] the current vaccines are not effective … we actually can come out with follow-up boosters, and rapidly get a new one out there. Already Moderna and Pfizer currently are working on that. They’re making booster shots that would be more effective against [these variants] in case it gets more able to overcome this current vaccine. 

TSL: How long would you estimate this vaccine rollout process will take in the United States?

LG: So right now, under emergency use authorization, it’s taken less than a year to actually have the vaccine designed, made and tested. In fact, the Moderna vaccine, they already had been working on the messenger RNA vaccines for about 10 years and had been in clinical trials. But when we had this emergency situation, the FDA said, “Okay, we’re going to speed up everything, and we’re going to give you emergency use authorization,” and we [were able to create a vaccine] within a year. But what we’re also [trying to figure out] at this point is: Can we always do it this way? Will this always work, for a rapid response? 

And in the case of Moderna, testing had been done for 10 years on the mRNA vaccines, but for a different disease. But now we’re actually saying, “Okay, let’s see if we can do it rapidly and safely and effectively.” And so far, the data is that way, but of course, the true assessment is going to be after a couple of years if we actually can get herd immunity and stop the disease.

TSL: Is there anything else you would like to add?

LG: I cannot overemphasize that this is not the last pandemic. This is not the last outbreak. If you go back and look at the number of outbreaks we have had over the last 10 years, of all different kinds of viruses, you are going to see a lot of outbreaks that we didn’t know how to respond to. So, what we really need to do is get our rapid response capabilities built up. I think that this is going to be the most important lesson that we are going to take home from this pandemic.

The good part is, I think, that we are going to have some good vaccine candidates, as you probably have seen, hundreds of new vaccine types that are out there that are fairly rapidly responding to this. Safety is the critical issue and the efficacy is what will show over time.

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