How Vaccines Train the Immune System in Ways No One Expected: Christine Stabell Benn (Transcript)

Arguments have become black and white.

Vaccines are good, vaccines are bad. There is no room for new perspectives. There is no room for our research findings. But for the next fifteen minutes, I ask you to kindly set aside any opinion you may have about vaccines and allow me to tell you what we discovered.

In Guinea-Bissau, we have a field station where we follow 200,000 people with regular home visits and we register all deliveries, all vaccinations, all hospitalizations, health center visits, all child deaths. And with this information we started doing what nobody else had done before us: we evaluated the effect of vaccines on overall health.

This may come as a surprise, but normally vaccines are not assessed for their effects on overall health. They’re only assessed for their protective effects against the vaccine disease. Everybody has been so convinced that vaccines only had protective effects against the vaccine disease, so it didn’t seem necessary to assess their effects on overall health.

But when we started looking at the effect of vaccines on overall health, it quickly became clear to us that there was something wrong. Something was simply missing in this equation.

Because some vaccines had a much bigger effect on overall health than could be predicted based on their specific protective effect, and other vaccines had much less effect than was expected.

So we realized that vaccines also affect the risk of other diseases. They had what we called non-specific effects. And with this insight, we started to look closer at all the childhood vaccines. We wanted to throw light on their non-specific effects.

Before I tell you what we found, I need to tell you, because it is very important, that there are two major types of vaccines: the live vaccines and the non-live vaccines. And they are fundamentally different.

The live vaccines contain a little bit of the weakened disease and it creates a mild natural infection in the body which is so mild that it usually doesn’t cause any symptoms. These vaccines are really good at stimulating the immune system, so you know them because these are the vaccines you only need one shot of to get a good protection.

The non-live vaccines also contain the disease, but only it has already been killed.

So the non-live vaccines, they also contain the disease, but it has already been killed. So these vaccines are not very good at stimulating the immune system, and you know that because these are the vaccines which you need several shots of, of the same vaccine, to get good protection.

But on the positive side, these non-live vaccines can never cause the real disease in the body. Not even in people with very weak immune systems, so most doctors prefer them over the live vaccines and nowadays most newly developed vaccines are non-live.

When you are born, your immune system is a beginner when it comes to battling infections. It’s like somebody who enters the tennis court for the first time and has to learn how to play tennis.

And the real infection, it is a really skilled opponent, which may beat the hell out of you and even send you off the court of life.

Live vaccines can be seen as a tennis coach who challenges you and makes you run around the court to return her strokes. Non-live vaccines, on the other hand, can be resembled to a tennis ball machine. You learn how to hit one particular stroke when the ball comes at you with a very specific speed, at a very specific spot.

Both types of vaccines create protection against the vaccine disease, but it turns out that they have very, very different non-specific effects.

And this is the moment to remind you that I asked you to set aside your opinions about vaccines for a full fifteen minutes. We have now evaluated 10 vaccines for their non-specific effects, four live and six non-live, and the results are very consistent.

All the live vaccines are associated with very beneficial non-specific effects. They improve overall health much more than could be expected, based on their protective effects. It is as if playing with a tennis coach teaches you a wide variety of new tricks, which make you able to combat all kinds of new and different opponents in the future.

Non-live vaccines, on the other hand, all have negative non-specific effects. They simply do not improve overall health as much as expected based on the protective effects, and, in fact, most of them have negative effects on overall health.

So to stick with the metaphor, playing with the ball machine only teaches you one particular stroke, so you are actually really ill-prepared and even worse off when a real opponent enters the court and the balls start coming and hitting elsewhere than what you trained for.

I’d like to give you two examples of the studies we did of these vaccines, and let’s start with a live vaccine, the live polio vaccine.

As I said in the beginning, nobody really expects any effect of this vaccine on overall health, because polio is almost eradicated. But when we tested the effect of live polio vaccine in Guinea-Bissau, we saw, in a randomized trial among newborns, that the newborns who were randomly allocated to live polio vaccine, their mortality was reduced by a third compared with the children who didn’t get live polio vaccine at birth.

This very big effect of live polio vaccine on the risk of dying was clearly purely non-specific – there was no polio. So live polio vaccine made the babies stronger and more able to combat all kinds of other diseases. We have seen these very beneficial non-specific effects of live polio vaccine in many other studies now and in even more studies, we have seen very beneficial non-specific effects of three other live vaccines – measles, tuberculosis and smallpox vaccines.

All the live vaccines seem to come with a bonus in the form of increased protection against a wide range of diseases.

Let’s take an example of a non-live vaccine, and there I would like to talk about DTP vaccine. It is a vaccine against three severe and potentially deadly diseases: diphtheria, tetanus and pertussis.

Before we started looking closer at DTP vaccine, it had only been studied for its protective effects. In one study, we went back to historical data, from when DTP vaccine was introduced in Guinea-Bissau in the 1980s, and the results were scary.

In spite of being protective against three deadly diseases, the introduction of DTP was associated with increased overall mortality. Children who received DTP vaccine had five times higher risk of dying than those who didn’t. And this is just one example of many studies now done of DTP vaccine and they all show the same: DTP-vaccinated children have higher mortality than those who didn’t get DTP.

So it appears that DTP vaccine has negative non-specific effects. The protection against the three deadly diseases comes at a very high price, namely increased risk of dying. So, with the best of intentions, the use of DTP vaccine may kill more children than it saves.

I know these results are extremely uncomfortable. And most people, including myself, just wish they weren’t true. But this is what the data tells us.

Intriguingly, the negative effects of DTP vaccine were strongest for girls, and that is a pattern we’ve seen for all the non-live vaccines. So for all six non-live vaccines, we’ve seen that they have very strong negative, non-specific effects in females, and we haven’t got a clue why, yet.

So, our findings can be summarized in one sentence. We discovered that vaccines train the immune system in ways no one expected. Overall, these results are fantastic in my researcher point of view, because they open for a whole new understanding of the immune system.

We used to think it was quite simple, and it turns out it is much smarter, it is much more complex than we ever imagined; it’s more like the brain. And the findings also open for completely new questions that we never thought about asking before, like: should boys and girls really have different vaccines, maybe?

Should we consider using live vaccines as immune trainer vaccines, even after their disease has been eradicated? And this is a characteristic of a really new research finding, it’s this ability to open new questions.

This finding really opens so many new interesting pathways. But they also have very important implications for health here and now. Because with this new knowledge, we can design vaccination programs much more efficiently. We can actually get much more health for the same money.

An Australian professor, Frank Shann, calculated, based on these observations, that if we modify the existing vaccination schedule in low-income countries, using the same existing vaccines, but just emphasizing live vaccines over non-live vaccines, then we could save 1.1 million children every year — 1.1 million children, that is equivalent to more than 3,000 children every day, with minor modifications of the vaccination program.

And you may wonder if this has implications in our part of the world, in high-income countries, and it does. Fortunately, the risk of dying from infections is low here.

But many get hospitalized. When we and others recently started to look for non-specific effects of vaccines on hospitalizations, we found exactly the same patterns. For instance, in a recent study from the U.S., children who had a live vaccine had only half the risk of getting hospitalized compared with children who had a non-live vaccine.

So it appears that also in high-income countries we can train our immune systems, we can make ourselves stronger against all kinds of diseases, with live vaccines. And this may have implications also for other types of diseases, more chronic diseases which depend on the immune system, such as asthma and allergies, autoimmune diseases, diabetes, cardiac diseases, even some cancers.

So what I am telling you here is that with this new knowledge, we can save millions of children in low-income countries and we can reduce disease burdens significantly in high-income countries. And this makes vaccines the largest untapped resource for improving health globally.

Now there is a “but” coming, you can feel it coming up, yeah. If only it were that easy. Because we are having a really hard time getting the world to listen.

Nobody ever proved that vaccines only have protective effects. And we’ve been accumulating data for 25 years now showing that vaccines have important non-specific effects. Yet, the world only focuses on the protective effects.

Our research results are not quite yet accepted. And I’ve spent literally years, I think, pulling out my hair and speculating why it’s so difficult to get these promising results acknowledged.

And I think the main reason is the polarized vaccine debate. The people who have the power to do something, to follow up and respond to these findings – the World Health Organisation and the health authorities, are all vaccine supporters.

And in my interpretation, they are reluctant to accept our findings because they imply the possibility that some vaccines may sometimes be harmful. So it is easier just to dismiss the whole thing.

The vaccine skeptics, on the other side, may find that our observations on non-live vaccines confirm their worst fears – vaccines can be harmful – but they may be more reluctant to accept the beneficial effects.

And their focus on the negative effects may make the vaccine supporters take an even more rigid stance. In my opinion, neither side is right or wrong. Both sides miss the new perspective. And meanwhile, the clock is ticking. Worst of all, we are missing out on the potential to save millions of children with minor changes to the vaccination program.

And things are moving in the wrong direction. Live vaccines are being stopped; more non-live vaccines are being developed. For instance, live polio vaccine has already been replaced completely by non-live polio vaccine in high-income countries. And the little girl you saw in the video in the beginning might be one of the last in the world to receive live polio vaccine, because the plan is to stop live polio vaccine completely by 2022 and replace it entirely with non-live polio vaccine.

Based on all the available data, this global switch from live to non-live polio vaccine will be a public health disaster.

So I am here with a plea for immediate action on the results we already have. I am here with a plea for more research into non-specific effects. We researchers, we have done the first steps.

Now, the engaged collaboration from the World Health Organisation, the health authorities, the funding bodies, the industry, is needed. You can help.

My talk is coming to the end, and you are free to pick up your opinions about vaccines again. But I hope I’ve inspired you to join me in the new era of vaccines as immune trainers.

Because with you on board, we are one step closer to benefiting from the full powers of vaccines.

Thank you very much.

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