How long does Zika virus immunity last?

06 February 2020

Interview with 

Alasdair Henderson, London School of Hygiene and Tropical Medicine

AEDES ALBOPICTUS MOSQUITO

Aedes albopictus (tiger mosquito)

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Zika virus, which is spread by mosquitoes and has been linked to birth defects including microcephaly, made headlines in 2015 when it began circulating in Brazil. Before that though, it had caused major outbreaks in Micronesia and Polynesia, the latter being the likely source of virus that spread to Brazil. Now, literally billions of people live within the “Zika belt”, the zone of the planet’s surface where people, the mosquitoes that spread it and the virus itself all co-exist. As such, disease monitoring, and development of effective vaccines are a priority. But working with blood samples collected over an extended period of time, as he explains to Chris Smith, Alasdair Henderson has found that something strange happens to a person’s immune response to Zika: it disappears...

Alasdair - So we looked at two countries that had Z outbreaks, and within approximately 18 months of those outbreaks ending, we found the number of people that still had antibodies against Zika much lower than we expected. It seems in both of these countries and both of these settings that adults in particular are losing their antibodies to Zika specifically.

Chris - And just to be clear, this is not normal for someone who's encountered a natural infection with a viral illness, is it? I mean, if we looked at measles, for example, we would find antibodies for life after that?

Alasdair - Yeah. Measles is a good example but also dengue, which is a closely related virus to Zika. We commonly assume that if you're infected with dengue, you are immune to that type of dengue for the rest of your life, which is what we expected to find with Zika. But our results didn't show that.

Chris - Interesting isn't it? Because Zika and dengue are actually quite close relatives aren't they? They're both flaviviruses, and they're not that different. So it's interesting that you've spotted this disparity?

Alasdair - Yeah, I think the fact that we worked quite well between some partners in Fiji and French Polynesia, and we found the same discovery in both locations, was really interesting.

Chris - I'm glad you brought up the location cause I was going to say where did you do the study and how did you do it?

Alasdair -  I am doing a PhD, which is kind of based in the Pacific, but specifically in Fiji. And there'd been two studies previously looking at different diseases in the past. So, in 2013, some researchers from the London school went and were studying typhoid and leptospirosis. There was then a big dengue outbreak. And in 2015 more researchers went out and sampled the same individuals to collect their blood and test for antibodies after the dengue outbreak. There was then some confirmed Zika cases, so I went out in 2017 and tried to find as many of the same people again. So we had serial blood samples from the same people.

Chris - So although blood had previously been collected for other purposes, you were able to go back and then look retrospectively for Zika antibodies in there and compare those historical samples with the ones that you got more recently?

Alasdair - Yeah. While it wasn't the focus of those original studies, they tested against a whole variety of viruses, um, at the same time and over time we found these interesting dynamics, particularly with Zika.

Chris - And how dramatic were the differences. If you look at the numbers of people who tested positive originally and then seemed to lose their antibodies, how many people was that happening to?

Alasdair - So if we look in Fiji specifically that 2013 study we found about approximately 6% positive for Zika. Two years later that number had gone up to 24%, and then two years after that we are expecting it to be at least 24 possibly higher. But we actually found that it had dropped to 12%.

Chris - And if you arranged people by age, was there any difference? Because we do know that people respond differently to infectious challenge at different ages. So can any of this be explained on the basis of the age of the individuals?

Alasdair - Yeah, it seems that way. We've shown here in adults that drop in antibodies seems to be where it's concentrated. But actually if you look at school children or children below 16, they keep their antibodies.

Chris - What do you think the mechanism of this is?

Alasdair - It's hard to say at this stage, but one of the possible mechanisms is, because people who are older are more likely to have had more infections over their whole life, including dengue, potentially, if you've had a lot of dengue in the past, you might not keep your Zika-specific antibodies as well as a child who might not have experienced as much dengue.

Chris - Does it also mean just because someone does record a low level of antibody, we know for example with other infections, chicken pox is quite a good example of this. There are some people in the population when we test them, they relentlessly test negative for chickenpox antibodies, but they don't catch it and it looks like they have, they have indeed had it in the past - they are immune, but they just don't come up on our tests. So are we seeing a sort of similar phenomenon here where we might have people that are actually immune to Zika, but they're not recording any demonstrable antibody levels?

Alasdair - Yeah, and I think that touches on this potential idea of cross protection. So, with Dengue there are essentially four types of dengue, and infection with one can lead to a period of cross-protection where you can't get infected with other types. We might be seeing a similar thing with Zika here, because we looked at two different tests. So one of them looked for a specific response to Zika that's called the MIA. And the other one looked at how well people's blood could neutralise each virus. And actually we found that people who were negative on the MIA - so didn't have specific Zika antibodies - still had quite high neutralizing antibodies. So whether that means that people are still able to fight off Zikar infection, we don't know, but it's indicative of that.

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