Gene Team

A Jan. 6  New York Times story reported US scientists' call for a national surveillance program to monitor the coronavirus genomes for new mutations, particularly in light of a new variant, known as B.1.1.7, surging in the United Kingdom, which appears to be more transmissible, as well as a variant in South Africa. According to the story, the US has only been sequencing a few hundred genomes a day for the international  GISAID database.

One of the scientists studying those genomes is Bette Korber, a Los Alamos National Laboratory fellow in the Theoretical Biology and Biophysics Group. Korber leads an interdisciplinary team that provides bioinformatics, theoretical and statistical support in collaborative efforts with experimental researchers, focusing on the areas of HIV-1 viral diversity, the human immune response to infection and vaccine design. Korber's own mosaic HIV vaccine concept is currently being evaluated in human clinical trials. She has received numerous awards for her work, including Battelle's Inventor of the Year in 2019, R&D Scientist of the Year in 2018 and the Secretary of the Department of Energy Award for her work on the Ebola Task Force in 2017. SFR spoke with Korber about SARS-coV-2 mutations, the GISAID database and her work. The interview has been edited for style, clarity and concision. 

SFR: Given that viruses constantly change, is the news of the UK and South African SARS-coV-2 variants solely notable because they appear more fast spreading?

Bette Korber: Solely is an odd word to me there. It does seem to me more fast spreading and the two variants are distinct, but…when you spot something that's different that seems to be coming up in frequency in the population anywhere in the globe, you want to take a look at it and understand what it means. So, you can verify in the laboratory if it really is more infectious. You can test if it has an impact on vaccines or convalescence sera so people who have been infected are likely to be quite well protected from subsequent infections, at least for a while—how well protected is still being sorted out.

A scientist in a recent  Science Magazine story said if B.1.1.7 does have a higher transmission rate, the trajectory of the pandemic could become less predictable than it's been. Does that seem correct to you?  

I guess so. We also found a strain that is more transmissible [D614G,  first identified by Korber and colleagues last spring] and it was very controversial when we first pointed it out, although there was extremely strong evidence for it. That strain was proven in the laboratory to be more…transmissible…and it's now the common form throughout the world. It's very difficult to say what the pandemic would have been had that transition not happened. People try to look at the transmission rates and use that in the epidemiological models, and when that changes you have to adjust the models and think about it differently. You might try to isolate the variant [as] they have tried to do in the UK…to limit travel so if this thing is really a problem, it stays more contained. Certainly, it has a presence in a lot of places. Whether it's increasing in those places remains to be seen.

It's going to take a few more months to really understand. It seems to me the really good thing is when they notice something like this, people start looking at it very carefully and trying to understand what that implies for the pandemic, for transmission and mostly for the vaccines. These aren't the only two variants in the world. This virus is evolving. All viruses evolve and this one is evolving slowly, compared to something like HIV or hepatitis. Sometimes the mutations are very, very rare, but they cause resistance to certain antibodies. If those mutations start coming up, you want to know it, you want to know what that implies. And I think the scientific community is trying really hard to look at this and be very systematic and be prepared.

Can you say a little about the importance of  GISAID in doing your work?

It's just extraordinary. GISAID [was founded] in response to influenza. Influenza also changes…so the scientific community around the globe collects sequences and they go into GISAID and people can analyze GISAID data to try to come up with the best vaccine for this year and to try to figure out if the vaccine needs to be changed up to be current. The science community at large has a lot of experience [with] a virus adapting to an immune response. So, when [COVID-19 happened], the scientific [community] adapted quickly to be able to accommodate this new virus and be able to collect sequences. People from all over the world were contributing sequences, and it was amazing. We got an excellent global portrait of the diversity of this virus.

In the fall, the UK has made a decision to really emphasize sequencing…I don't know why the submission has gone down in other places, but it has really skyrocketed from the UK. The US has also really stopped sequencing to the level it had been. I think this is a serious problem because now is exactly the moment we need the sequences, and when I say 'we,' I mean the global scientific community, because we're rolling out the vaccine and we want to make sure nothing changes that would impact the efficacy, the beautiful protective effects of that vaccine.

Is that how New Mexico would know if the strain was here?

I have a special site that I look at for New Mexico and I'm on the safety board for the state, so I'm keeping an eye on it, but I can only look at what's in GISAID, and New Mexico hasn't been submitting very much to GISAID. I've been hoping we'd get more out in talking to people about that. We can monitor if there's a change in the community in New Mexico that might be relevant, but the only way I personally can do that is by having the data in GISAID.

I watched a  talk you gave for the Human Vaccine Project last spring where you described GISAID as a firehose of data. How do you take in that much information?

I have this wonderful colleague named Will Fischer and another wonderful colleague named Hyejin Yoon, and they are very excellent computer scientists. We have a very nice relationship with GISAID…and they make daily updates and they provide [all the new sequences] to Will [who] filters out the problematic sequences… and he makes automated alignments and makes a phylogenetic tree and then he organizes the sequences by their relationship through that tree…he provides those to Hyejin and Hyejin I have worked out all of the tools you see on [ https://cov.lanl.gov] and there are a lot of tools for tracking mutations. Both [Fischer and Yoon] worked incredibly hard to accommodate the data, and it becomes difficult because a lot of our codes, when it hits 250,000 sequences, if you want to build a phylogenetic tree, it becomes very computationally intensive.

You've designed  an AIDS vaccine that's currently undergoing human clinical trials. Why has it taken a lifetime to design an AIDS vaccine and less than a year to design one for COVID-19?

There are two elements to this. One is some of these methods [for the coronavirus vaccines] have been studied in HIV and other vaccines venues…so the delivery strategies…were kind of ready. An even more critical aspect is this virus evolves very slowly where HIV evolves incredibly rapidly.

Has the COVID-19 pandemic impacted the work on HIV?

For the study in South Africa, COVID came up and they were almost done…but people are afraid to go into the clinic…so they put extremely safe mechanisms…in place and they finished the study under the stress of COVID; it was a heroic effort and a beautiful effort. The study in the Americas definitely got slowed down…but it's been re-initiated. I'm hopeful. HIV is still killing vast numbers of people and it would be wonderful to have the vaccine.