Researchers at Imperial College London have discovered a new way
in which a very common childhood disease could be
treated.
In the first year of life, 65 per cent of babies get infected by
Respiratory Syncytial Virus (RSV). This causes bronchiolitis, and
is thought to kill nearly 200,000 children every year
worldwide.
In 1966 and 1967, vaccines were tested for RSV. These had
disastrous effects on the immune response, leading to a worsening
of the disease and, in many cases, death.
Scientists have so far not been able to fully explain this
effect, which continues to hold back vaccine
development.
Studying this effect in mice, Imperial's Professor Peter
Openshaw and his team developed a new technique which they hope
might be used in tackling a wide range of other diseases including
viral bronchiolitis.
The researchers examined how the RSV vaccine boosts white blood
cells that respond to infection, making them flock to the lungs and
blocking the tubes that supply oxygen. They found that the
vaccine boosted the accumulation of these T cells, but also
virtually eliminated the regulatory immune response in the lungs
caused by cells known as Tregs.
Professor Openshaw said: "The reason for the vaccine's failure
has been a puzzle for over 40 years. To solve it, we tested out new
ideas about how the immune system slows down inflammation. If it
doesn't regulate itself properly, inflammation can run out of
control. This vaccine seems to have locked the accelerator in the
on position and to have disabled the brakes."
Next, the team tested the effects of chemokines, proteins
which cause nearby cells to move from place to place in the body.
They found that when vaccinated mice inhaled the chemokines, Tregs
were attracted back into the lungs where they reduced inflammation
and helped to fight infection.
Professor Openshaw added "This is a very important discovery -
it represents an entirely new way to treat these inflammatory
diseases."
If this approach were to work in patients, it could be used in a
wide range of conditions in which there is excessive inflammation
such as arthritis or psoriasis, as well as
bronchiolitis.
Professor Openshaw's group hopes that by gaining a better
understanding of RSV disease they may at last be able to understand
why some babies get so seriously ill, whereas others make a quick
recovery. This knowledge could help to reduce RSV's global impact
and could lead to the development of safe, and effective,
vaccines.
The paper, Defective immunoregulation in RSV vaccine-augmented viral lung
disease restored by selective chemoattraction of regulatory T
cells, is published in Proceedings of the National
Academy of Sciences.