Some vaccines seem to provide us with a host of extra benefits. Is it time to see the cornerstone of modern medicine in a new light?
Editorial: "Silence isn't golden when it comes to vaccines"
HAVE a look at your left shoulder: if you are past your mid-twenties it almost certainly bears a circular scar. Do you remember how it got there? You queued up in the school hall, perhaps, or outside the nurse's office, watching your friends rubbing their arms as they walked away, relieved at having survived their BCG jab.
The Bacille Calmette-Guérin vaccination was given to protect you from tuberculosis. What we are only just realising is that, in common with several other vaccines, it may have done far more than that.
There is growing evidence that vaccines have a wider-ranging influence on the immune system than we thought. In Africa, for instance, studies have shown that measles vaccine cuts deaths from all other infections combined by a third, mainly by protecting against pneumonia, sepsis and diarrhoea.
Even in the West, where it is far less common for children to die from infectious illnesses, there are still surprising benefits: some vaccines seem to reduce our susceptibility to eczema and asthma. Exactly what causes these "non-specific effects", as they are termed, is a mystery. But some scientists are arguing that, despite the uncertainties, it is time to start harnessing them more effectively.
The World Health Organization, which is the main provider of vaccines in developing countries, has asked a group of vaccine experts to get to the bottom of it. "This could have huge implications for global healthcare," says Christine Benn, a senior researcher at the Statens Serum Institute in Denmark and a member of the WHO committee. "Vaccines have been a fantastic success, but we can probably do much better by taking non-specific effects into account. An examination of these issues is long overdue."
Considering vaccines have been used since the 1800s and are the central plank of our public health system, it may seem hard to believe that such profound effects could have gone ignored all this time. In fact, an early 20th century Swedish physician called Carl Näslund did notice something was up after the BCG vaccine was introduced in his country. Vaccinated children had a much higher chance of reaching their first birthday – even though TB normally kills older children.
In the 1940s and 50s, trials in the US and UK suggested that BCG-vaccinated children had a 25 per cent lower death rate from diseases other than TB. But no one took much notice until 30 years ago, when a Danish anthropologist called Peter Aaby began working in the West African state of Guinea-Bissau. In 1979 he witnessed a severe measles outbreak that killed 1 in 4 infants affected. Aaby arranged for measles vaccination to be introduced, but was surprised to see that even after the epidemic abated, immunised children were more likely to survive childhood. Aaby began digging, and discovered studies from elsewhere in Africa, as well as Bangladesh and Haiti, that also suggested measles vaccine gives a wider kind of protection. "We are collecting more and more data consistent with non-specific effects being very important," says Aaby.
What could the explanation be? Several lines of evidence suggest that our immune systems can be affected by many factors, including past encounters with microbes. Those microbes can be in the environment or a vaccine syringe. "If infections can alter the immunological milieu, it is not a major leap to suggest that vaccines might also do so," said Andrew Pollard, head of the Oxford Vaccine Centre at the University of Oxford, in an editorial about Aaby's work last year.
According to the old view of vaccines, they work by priming what is known as our adaptive immune system. This consists of various defence cells circulating in the blood, which make antibodies and other molecules that recognise and latch on to specific foreign proteins on bacteria, viruses or other germs.
It is this lock-and-key specificity that is responsible for our immune memory. On our first encounter with the measles virus, say, the immune cells that make potent antibodies to it reproduce, giving rise to successive generations of daughter cells that make progressively more powerful antibodies. The end product is highly proficient measles-killing machines that linger in our bodies for years. That's why, if we re-encounter the virus, it is defeated so quickly we don't even notice.
But that may not be the whole story. Another, evolutionarily older, branch of our defences known as the innate immune system might also be playing a role. These cells are programmed to react to anything unfamiliar or untoward, such as the chemicals released when tissues are damaged, attacking any molecules or microorganisms that might pose a threat. Last year, surprising evidence emerged that BCG stimulates the innate immune system as well as the adaptive one.
In people who received the shot, certain kinds of innate immune cells responded more strongly to bacterial and fungal pathogens completely unrelated to the TB bug. This is the first indication that the innate immune system reacts to vaccines, and the researchers suggested it could explain some of the general immune-boosting effects of BCG. "It's quite preliminary data, but it's very important," says Nigel Curtis, head of infectious diseases at the Royal Children's Hospital Melbourne and the University of Melbourne, Australia, who studies BCG.
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