Respiratory syncytial virus vaccine development

Published on June 24, 2015   43 min

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I'm Peter Openshaw. I'm the Professor of Experimental Medicine at Imperial College London. And I've been working on Respiratory Syncytial Virus for more years than I care to remember, actually, since about 1985. And what I'm going to do today is to summarize some of the most important background about RSV, talk a bit about animal models for vaccine development, and then the current vaccines that are under development, and where I think the vaccine field is going in the future.
So first a bit about Respiratory Syncytial Virus. It was first named the Chimpanzee Coryza Agent by a group that had been studying chimps and found that some of the chimp handlers had common colds and that the chimps had common colds, too. It was subsequently renamed, Respiratory Syncytial Virus by Bob Chanock, but I think that the name is a very regrettable one. I think that if instead it had been called, the "Savage Agent," the whole history of RSV research would have been changed. I've been trying to get the name changed to the Savage Agent, but nobody seems to take this very seriously.
Respiratory Syncytial Virus, quite extraordinarily a successful virus. It's distributed worldwide. In temperate climates, it tends to undergo winter epidemics. So every winter we know there's going to be a big outbreak of RSV disease. And hugely successful in that it manages to infect about 65% of children the first year of life. By the third year, it up to about 96%. So virtually everyone gets infected, and everyone gets reinfected, as well. So if you take adult volunteers, you put RSV into the nose, you tend to again get a common cold. So that's atypical. Or most viruses, if you infect once and then try and infect again, you won't be successful. So it's a very intriguing virus immunologically. It's usually a mild disease, but because it infects so many children, it's actually a major cause of hospital admissions. So in many parts of world, it's the commonest single cause of hospitalization during infancy. And, as I said, it causes about 70% of cases of bronchiolitis. So in us, it just causes coughs and colds, but it's obviously a danger to younger children, in that we can transmit that cough or cold to them. There's also an association with wheezing, which I'll talk a little bit more about later.
A bit about the actual disease that it causes in the lung. This is a picture of a bronchial from a child that actually died of a road traffic accident after being seen in hospital with bronchiolitis and being sent home. And although the child wasn't terribly ill, you can see that this airway, which is normally just full of air, is packed full inflammatory cells. And the surrounding tissue around the bronchial is infiltrated with cells which have migrated out from the arterioles and caused this profound inflammation. So it's really an inflammatory disease caused by the host's reaction to the virus.
Children are typically born with reasonably high levels of antibody. And this is a gift from their mother. It's transferred through the placenta and also through the mother's milk. So breastfeeding is protective. But these maternal antibodies wane as time passes. So the children aged six to nine months have quite low levels of antibody, and start getting antibody again as they become infected. So these are children who have been infected during this window of susceptibility and then have developed their own antibody.
So that pattern of immunity, with maternal gift waning during the first couple of months, leads to a sharp rise in the instance of bronchiolitis, which tends to peak at about three or four months of age. So the frequency of bronchiolitis then declines, so that's after 12 months, it's very unlikely that a child who becomes infected, even for the first time, is then going to suffer from bronchiolitis. So there seem to be critical postnatal developmental stages that may be in the immune system, may be in the physiology of their respiratory tract that make these children particularly vulnerable in this period to suffering bronchiolitis, and therefore, hospital admission.
So that describes what happens in temperate countries. It's only recently that we've become aware that RSV has such a big impact in the developing world. And this has come about particularly from studies which have been done in sub-Saharan Africa, and in places where normally it hasn't really been thought vital that we diagnose what it is that's causing the respiratory diseases that are so common amongst children in those parts of the world. And these studies that were highlighted in articles, in journals like the Lancet over the past five years, in particular, show that about 99% of all the deaths in the world due to RSV in childhood, are in these developing countries. The distribution tends to be a little different from what we see in the developed world, in that children up to the age of five are actually quite vulnerable. And I think that this really changes the landscape in terms of where we would like to vaccines from being amongst babies in developed countries, through to being in children up to the age of five in the developing world.

Respiratory syncytial virus vaccine development

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