S1E62 / South Africa’s B.1.351 Variant — Immunity-Evading / Salim Abdool Karim, Richard Lessells, Jinal Bhiman, Allison Greaney

Just Human.

If you have a strain like the South African one, which has resistance to vaccine-elicited antibodies, that is concerning.

So being reactive to that problem is very challenging, and it just highlights to me that we've got to get ahead of the virus.

Welcome back to Epidemic, the podcast about the science, public health, and social impacts of the coronavirus pandemic. I'm your host, Dr. Celine Gounder. Salim Abdul Karim is the director of the Center for the AIDS Program of Research in South Africa, CAPRISA. He's also the CAPRISA Professor for Global Health at Columbia University. So do you go by Slim or do you go by Salim?

Everybody just calls me Slim, but my correct name is Salim. Yes.

Okay.

Either is fine. I don't care. I'm agnostic as to which is used.

Okay, great.

Back in April of last year, near the start of the pandemic, Slim and his colleagues had started collecting samples of the coronavirus in South Africa. They were looking for new variants. This sequencing was happening a floor below Slim's office at the KwaZulu-Natal Research and Innovation Sequencing Platform, or KRISP.

And once a month, the director of KRISP, Professor Tulio de Oliveira, would come up and he would sit and go through the data with me, and we would look at how the virus was evolving in South Africa and indeed in the world.

They were looking for hints about how the virus may be changing as it was spreading through South Africa. The country was hard hit at the start of the pandemic, but there really wasn't much to see in these meetings.

In fact, by about September, I was saying to him, I'm not sure why we're still meeting because this virus doesn't seem to be changing very much.

But as cases were falling across much of South Africa, there was a strange uptick in Nelson Mandela Bay.

And it It was just around a couple of months after they'd come out of the first wave and it was kind of coming into summer. And so it was kind of unexpected that we're getting this early resurgence.

This is Richard Lessells. He's an infectious disease specialist and epidemiologist who also works at CRISP.

They had a feeling that there was something different about the disease they were seeing in the hospitals and that they were seeing more severe disease in younger people.

By now, South Africa was getting ready for the Christmas holiday, and summer was about to start in the Southern Hemisphere. One day in late November, Richard saw Tulio, the guy in charge of the sequencing project.

Tulio and I are close friends. We work closely together and we have neighboring offices. And he appeared at the door of my office. And anyone who knows Tulio knows that he's a brilliant, lively chap. And he just, he looked scared.

When he came to see me, I could see he was ashen pale as he walked through the door. He sat down, put his computer on, and he showed me the data. 23 mutations. I just fell. I said, "What? We've never seen something like this before." There were 3 mutations that stood out.

They were all on the spike protein, the part of the virus that attaches to human cells.

I looked at that and I said, this does not look good.

They named the variant 501Y.V2. This new variant was more transmissible.

We estimate its transmission is about 50% faster. For example, in the Western Cape, it took 107 days to reach 100,000 cases in the first wave. In the second wave, a mere 54 days. 50% faster.

But it had another troubling mutation. It appeared that it was evading the body's immune response. So as he's sharing this with you, what is going through your mind?

Uh, do you want me to be honest?

I mean— Yes, be honest.

I mean, first of all, that we weren't going to get any rest over the Christmas period because it was clear that we were going to be working on this nonstop. Certainly, I was very alarmed because it was immediately clear that the health system was going to be stretched beyond what it had been in the first wave and that we were going to see a large number of deaths. And unfortunately, that was the case.

This is the second in our series on variants of concern. Our previous episode looked at the UK variant, and today we're looking at the variant that emerged in South Africa. The 501Y.V2 variant Tulio and Slim discovered was first reported in the United States in January. At this time, it's not yet widespread here, but it poses serious challenges to any country. In this episode, we'll look at the science behind why this strain from South why South Africa is so dangerous.

So it's been quite a terrible start to the year here in South Africa. Our healthcare systems have been overwhelmed. We've had so many deaths, many, many, many deaths.

Why it poses a risk to everyone.

Yeah, it's possible that people who have been previously infected with SARS-CoV-2 may now be susceptible to some of these new variants.

And what it means for our vaccines.

Could the virus escape immune responses, both natural immunity and vaccine-induced immunity?

Today on Epidemic, the rise of the South Africa variant. The 501Y.V2 mutation could not have come at a worse time for South Africa.

Because it kind of emerged and really started taking off November going into December, That for us, the end of the year is of course summer and summer holidays.

This is also when a lot of migrant workers leave South Africa. This led to a resurgence in cases in neighboring countries.

It just shows how difficult it is to be reactive with this virus. By the time you've detected something and understood the significance of it, you're already several steps behind the virus.

Richard says it's no accident that South Africa was one of the countries where new variants emerged.

The kind of common features between South Africa and the Eastern Cape in particular and Manaus in Brazil, where this P.1 lineage has emerged, are that they were very heavily affected in the early parts of the epidemic in the first wave.

The same goes for the variant out of the UK and, as we're starting to learn, the United States as well. As the coronavirus spreads, researchers are discovering similar mutations again and again, even though they're happening halfway around the world.

What we're seeing is that the virus is evolving in similar ways in many different parts of, of the world, and I think that To us, that wasn't surprising because I think what we were starting to understand and realize that this is essentially what's called convergent evolution.

So the more the coronavirus has a chance to spread and multiply, it's finding new and better ways to get into our bodies and make more copies of itself.

But they are converging around some key mutations. And two of those key mutations seem to be at positions 501 and at position 484.

These points on the spike protein are called the receptor binding domain. That's the part that grabs on our cells and lets the virus in.

The mutations at position 501 seem to impact binding affinity and seem to be increasing transmissibility of the virus.

This is similar to the mutation we talked about last week with the B.1.1.7 variant from the UK. This adaptation helps the virus spread faster.

The mutations at 484 also impact binding, but importantly, mutations at 484 seem to also confer a significant amount of immune escape.

Janelle Beaman has been studying this too.

I am a medical scientist at the National Institute for Communicable Diseases in South Africa.

Janelle and her colleagues looked at blood samples from people who'd been infected with an older strain of coronavirus. They found out the antibodies those people had from their earlier infection were less effective at fighting off the new 501Y.V2 strain.

So we tested 44 samples, and in almost half of those samples, there was a complete knockout of neutralizing activity, which means that the antibodies that those people developed were not effective at all at preventing the new variant from infecting cells. And then in the other cases, there was between 3- and 64-fold reduction in activity. It's really not something insignificant.

It could mean that people who've already had COVID and have some antibodies to the virus could get reinfected.

If I can kind of put it into perspective, when we think about changing antigens for an influenza vaccine, if there is a difference in reactivity between the currently circulating strains and the previous vaccine strain of an average of 8-fold, then that calls for a change in the strain that's used in the vaccine. And that actually is the average for the samples that we've tested here.

And what went through your mind when you, you know, as you're thinking about the implications of this?

So I think for me, the biggest concern was about vaccine efficacy.

So what does this mean for our vaccines? We'll talk about that after the break. Before the break, Janelle told us that antibodies from the previous strain of coronavirus saw a significant decrease in their ability to fight off the new variant. So how exactly does the South Africa variant get around the immune system?

There are some mutations that you may have heard of, such as E484K, that seem to reduce the ability for antibodies to bind and neutralize the virus.

Allie Graney studies how SARS-CoV-2 attaches to cells.

And I'm a graduate student in the lab of Jesse Bloom at the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Just like the spike protein can grab onto our cells, antibodies need to find ways to grab onto viruses before they can kill them or neutralize them. At its most basic, this is all like a puzzle. Every bit of a cell or a virus has a unique shape. Like a puzzle piece. All those shapes need to fit together just right in order to work. But when a virus mutates—

On like a very small scale, it can change the shape of the protein.

So a protein that used to fit suddenly doesn't.

And that change can kind of make it harder for antibodies to bind to the virus. So it kind of changes a biochemical property of the protein that can alter other interactions.

That's what's happening with the South Africa variant. Antibodies from people previously infected are looking for a certain puzzle piece on the coronavirus. But they can't find it. They're still looking for the old piece that no longer fits. Now, some antibodies will still manage to find and neutralize the variant. But the body needs a whole lot more antibodies to make up for all the others that don't recognize the new coronavirus strain.

And so if we see a 10-fold drop in neutralization, that basically means that we need 10 times more of that plasma to stop the virus from entering cells.

This matters because there's a threshold for how many antibodies are needed to successfully fight off coronavirus. That threshold is called a neutralizing titer.

People who, who get infected with SARS-CoV-2 have fairly variable immune responses. But it's, it's pretty variable, and some people have really good immunity and some have less good immunity.

Think about that old line: an apple a day keeps the doctor away. Let's pretend there's a certain number of apples that represents the neutralizing titer to stop coronavirus. One person has 10 apples, another has 5 apples, and the third has no apples. Right now, the person with no apples would get sick. They don't have any protection. But the two people with apples already got COVID. They have enough immunity to be protected against the past version of coronavirus, at least for a little while. But let's say the variant from South Africa can evade this apple immune system. The body would need 5 more apples than normal to fight off the virus. The person with 10 apples can lose 5. And still have enough to stop the virus. But the person with only 5 apples? They're out of luck. That extra demand on the immune system means they no longer have what it takes to stop the virus from reinfecting them. This is where vaccines come in.

And so it seems like most people who get vaccinated get really good responses, and it's all fairly similar across the board. In general, the vaccine-elicited immunity seems to be as good or in some cases better than natural infection.

Because SARS-CoV-2 is a novel virus, we don't know yet what that magic number of apples is for protection. That's why the immune response from a vaccine gives people a better chance of fighting off the virus, regardless which variant they may be exposed to. And that's also why it's important for everyone to get vaccinated, even if they've already had COVID. Different vaccines offer differing levels of protection against the variants. Here's Salim Abdul Karim again.

For example, for the Pfizer and Moderna vaccines, laboratory assays have shown that the antibodies that they have in the serum do not have the same level of neutralizing activity against the 501Y.V2 variant. Fortunately, these antibodies seem to generate pretty high levels of antibodies, so even though the concentrations required are higher, it seems that they may be able to kill the virus anyway. However, the most disturbing news came when we saw the results of the Novavax trial, which found that that vaccine was 89% efficacious in the UK but only 49% efficacious in South Africa. That is a deeply concerning result. It suggests that what we're seeing is a drastic difference in immune capability of these vaccines.

And those concerns came to a head in South Africa this month. Well, South Africa has suspended its rollout of the Oxford-AstraZeneca coronavirus vaccine.

A trial of 2,000 people there found AstraZeneca much less effective against the South African variant, offering minimal protection against even mild disease.

South Africa received more than a million doses of the vaccine and had planned to to start inoculating frontline healthcare workers in the coming days. After we spoke with our guests, South Africa's government suspended the rollout of the AstraZeneca Oxford vaccine. Salim explained the decision in an interview with DW News.

Efficacy against mild disease is quite low, and that's supported by laboratory evidence as well. Now we are uncertain about whether the AstraZeneca vaccine also prevents severe disease and hospitalization against the 501Y.V2 variant that is prevalent in South Africa. And so in that kind of uncertainty, we thought it prudent to put a delay on the rollout of the AstraZeneca vaccine.

The data out of South Africa about the AstraZeneca vaccine has led some to worry about vaccine access in less developed countries. The AstraZeneca vaccine is a major component of the World Health Organization's COVAX efforts to get vaccines to nearly 100 countries. But in the same interview with DW, Slim says South Africa's experience does not necessarily apply to the rest of the world.

Because the 501Y.V2 variant, which is the variant that is able to escape immunity, constitutes about 80 to 90% of our circulating virus. So our situation is different. Our decisions should not really apply to other centers and other countries unless they also have a dominance of the same variant.

At this recording, the South African government is still planning to move forward with vaccines from Johnson Johnson and Pfizer in the coming weeks. Both of these vaccines have shown the ability to reduce severe disease, hospitalization, and death, even though they're less effective in preventing infection with the South Africa variant. Slim says it's critical to get these vaccines out, even if they offer different levels of protection.

It's better to immunize more people with partial protection than to immunize a small proportion of people with very high levels of protection.

As we discussed in our previous episode on the UK variant, the more people who have some partial level of protection, the more likely the virus will change again.

What we are likely to see is a new tit-for-tat process where with vaccination-induced immunity there will be immune pressure on the virus to change, and with those mutations we're likely to see varying levels of immune escape, the extent to which the efficacy of the vaccines becomes compromised. It will require that we generate new versions of the vaccines and give them as booster doses.

But in the meantime, there's a lot we can do to protect ourselves and each other.

In order to do that, we've got to use our full prevention toolbox. We've got to use the vaccines we have, the prevention tools of masks and social distancing and hand hygiene, etc. Those in combination will give us our best shot at trying to reduce viral transmission and try and achieve as close as possible to viral control.

Cases are still high, but it looks like South Africa's second wave has started to recede. And that has Janelle feeling hopeful.

I hope that that means that people have started realizing the impact that this thing is having on our communities.

But this pandemic is a marathon, not a sprint. We all know what we have to do to slow the spread of the virus, but we have to stay committed until everyone is vaccinated.

So I hope that things are going to change going forward, and I, and I also hope that when we get into our lull period, that people don't forget what happens when you don't follow protocol, and that people will just be steadfast Epidemic is brought to you by Just Human Productions.

We're funded in part by listeners like you. We're powered and distributed by Simplecast. Today's episode was produced by Zach Dyer and me. Our music is by The Blue Dot Sessions. Our production and research associate is Temitayo Fegbenle. Our interns are Annabel Chen, Brian Chen, Julie Levy, and Sophie Varma. If you enjoy the show, please tell a friend about it today. And if you haven't already done so, leave us a review on Apple Podcasts. It helps more people find out about the show. Follow Epidemic on Twitter and Just Human Productions on Instagram to learn more about the characters and big ideas you hear on the podcast. We love providing this and our other podcasts to the public for free, but producing a podcast costs money, and we've got to pay our staff. So please make a donation to help us keep this going. Just Human Productions is a 501(c)(3) nonprofit organization, so your donations to support our podcasts are tax deductible. Tax deductible. Go to epidemic.fm to make a donation. That's epidemic.fm. And if you like the storytelling you hear on Epidemic, check out our sister podcast, American Diagnosis. On American Diagnosis, we cover some of the biggest public health challenges affecting the nation today. Past seasons covered topics like youth and mental health, the opioid overdose crisis, and gun violence in America. I'm Dr. Celine Gounder. Thanks for listening to Epidemic.