Measles jab less effective after caesarean section

Researchers at the University of Cambridge and Fudan University in China have found that the first dose of their measles jab is almost 3 times more likely to be completely ineffective in children born by C-section compared to those born vaginally. Henrik Salje, from the University of Cambridge’s Department of Genetics, suspects that differences in the microbiomes of babies born via the two different routes might be at the heart of it. As measles cases continue to rise around the world, it’s an important health issue to bear in mind…

Henrik - Measles remains a really big problem around the world. About 130,000 people die each year from measles, and we have a very good vaccine, but for some reason or other, sometimes when we vaccinate infants, they actually are not protected afterwards. That's always been a bit of a mystery. And so what we did was to try and understand why it is there are these infants, we think they're protected, they're vaccinated, but in fact they're not.

Chris - How did you pursue it?

Henrik - We worked with a cohort of children. What that means is, right from birth, a group of babies were followed up over time. What this team in China did is they collected blood at very regular intervals, they then noted down when these infants got vaccinated and, in the blood, we could then see whether or not they had protection to measles, including before and after vaccination. This allowed us then to identify those infants that actually failed to mount an immune response following vaccination, as well as to carefully monitor how antibodies in general change over time, including from maternal antibodies that are given from mothers at birth, and also then how your maternal antibodies post vaccine change over time.

Chris - Did any of the vulnerable individuals, the ones that you were documenting, an apparent absence of measles immunity, then go on to catch measles?

Henrik - No. So, in measles generally, it tends to have big outbreaks and then you have no circulation for long periods of time. In this case, there wasn't a measles outbreak. Fortunately, these individuals did not develop measles, so far that we could tell anyway. Also, very importantly, like most countries in the world, in China you have two doses of the vaccine and all the individuals who failed that first dose ultimately got protected with their second dose.

Chris - So it's not that you ruled out, if you get vaccinated and you don't respond, you're never going to, it's just a question of you having more and it pushes those stragglers over the immune line.

Henrik - That's exactly it. That's something we've generally always known is that, that second dose is often just to pick up those individuals who failed that first vaccination. That's certainly the case here as well.

Chris - So what we'd like to know is what's special about those people who were the primary first vaccine failures, what connects them, and what might we be able to do about it?

Henrik - Absolutely, yes. This is probably true not just for measles but for again many other infectious diseases. What we did is we just really looked at all possible reasons, hypotheses as to why some people may fail a vaccine and others not who otherwise look completely identical. The only thing that came out was the mode of delivery of those babies. What we found is, babies born through c-sections were around two to three times more likely to fail their vaccine compared to babies born through vaginal delivery. Even though the vaccine is happening many months later, it seemed to have this long-term effect on the ability for you to mount an immune response.

Chris - Indeed, we give that MMR vaccine at least a year or more, don't we, in this country at least. So why do you think there might be that connection to caesarean section then?

Henrik - That's completely true, and I think there's another whole group of people who maybe don't mount such a high immune response, and that's really to do with this reason: we'd wait for a year in the UK. That is, we have these maternal antibodies which are passed from your mother to the baby, and they're fantastic, they protect you, but they're also very good at stopping the vaccine from having its desired effect. So, what we do is we tend to wait until those maternal antibodies are very low, and that's where we wait for a year in the UK and in many other countries too. But this seemed to be something completely independent to that, and I think what we are slowly discovering more and more is something called the gut microbiome. What this means is all those friendly bugs which help you in all sorts of aspects of your daily life, including the development of immunity. What happens is that mothers have a vaginal microbiome which gets passed on to the infants at birth. If you're having a c-section, you're completely circumventing that, so you don't have that early microbiome that you would do otherwise.

Chris - Some people say that's the most important meal you'll ever eat, don't they? They say your first taste of life is a mouthful of muck, but it's absolutely critical for good health. But how do you connect then what the microbes are doing with response to a vaccine? Because you're still running into all kinds of other infections as a little kid and they don't seem to behave differently, or do they?

Henrik - That remains an excellent question and a very open question. We weren't able to really tackle that through this study. Certainly, it's something which we will need to focus on more: what is the mechanism by which all this muck which, as you say, we now have from the very earliest stage of life, really develops, or allows you to develop immune responses going forward. It seems to be relevant not just for measles, but really all those different vaccines and all the different infections. What's really comforting is that those individuals who are born through c-section failed their vaccine, they ultimately did respond. I think what's happening is it's taking longer for you to develop the appropriate microbiome. Certainly you don't want to be too worried that, in the long term, you won't be able to mount an immune response, but it just takes a bit longer. Another point to note is that in the UK we wait until three to five years for the second dose. We're having increasing rates of c-sections, about 3 in 10 babies are born through c-sections these days in the UK, so it might be that from a policy perspective we might want to consider shortening that for infants born through c-sections

Chris - Because epidemiologists have connected other health outcomes to caesarean section as well, haven't they? Things like, a greater risk of allergy in later life, more risk of getting gastrointestinal problems as you get a bit older. There does appear to be something going on. How are you going to try and pursue this, then? Are you going to try and get underneath what that connection is between what's going on in the gut and how the immune system is maturing?

Henrik - That would be wonderful. I think there are a number of ways you could continue this study and we will certainly do so. One is better characterisation of this microbiome, both in the mother and the baby, and seeing how that develops in the first few weeks and months of life, seeing how it changes then following vaccination, following infection. I think that will give us a more complete picture. At the moment, this is really, ultimately, an observation. We see some babies that failed their vaccine and we just see how they're different from ones that don't. But now what we need to do is do some more detailed studies that really try and understand why.