Public
release date: 29-Jan-2012
[ |
E-mail
| Share

]

Contact: Craig Brierley
c.brierley@wellcome.ac.uk
44-207-611-7329
Wellcome Trust

Genetics has provided surprising insights into why vaccines
used in both the UK and US to combat serious childhood
infections can eventually fail. The study, published today in
Nature Genetics, which investigates how bacteria change
their disguise to evade the vaccines, has implications for how
future vaccines can be made more effective.

Pneumococcus (Streptococcus pneumoniae) causes
potentially life-threatening diseases including pneumonia and
meningitis. Pneumococcal infections are thought to kill around
a million young children worldwide each year, though the
success of vaccination programmes has led to a dramatic fall in
the number of cases in countries such as the UK and US. These
vaccines recognise the bacteria by its polysaccharide, the
material found on the outside of the bacterial cell. There are
over ninety different kinds ? or 'serotypes' ? of the bacteria,
each with a different polysaccharide coating.

In 2000, the US introduced a pneumococcal vaccine which
targeted seven of the ninety serotypes. This '7-valent' vaccine
was extremely effective and had a dramatic effect on reducing
disease amongst the age groups targeted. Remarkably, the
vaccine has also prevented transmission from young children to
adults, resulting in tens of thousands fewer cases of
pneumococcal disease each year. The same vaccine was introduced
in the UK in 2006 and was similarly successful.

In spite of the success of the vaccine programmes, some
pneumococcal strains managed to continue to cause disease by
camouflaging themselves from the vaccine. In research funded by
the Wellcome Trust, scientists at the University of Oxford and
at the Centers for Disease Control and Prevention in Atlanta
studied what happened after the introduction of this vaccine in
the US. They used the latest genomic techniques combined with
epidemiology to understand how different serotypes of the
pneumococcus bacteria evolve to replace those targeted by the
initial vaccine.

The researchers found bacteria that had evaded the vaccine by
swapping the region of the genome responsible for making the
polysaccharide coating with the same region from a different
serotype, not targeted by the vaccine. This effectively
disguised the bacteria, making it invisible to the vaccine.
This exchange of genome regions occurred during a process known
as recombination, whereby one of the bacteria replaces a piece
of its own DNA with a piece from another bacterial type.

Dr Rory Bowden, from the University of Oxford, explains:
"Imagine that each strain of the pneumococcus bacteria is a
class of schoolchildren, all wearing the school uniform. If a
boy steals from his corner shop, a policeman ? in this case the
vaccine ? can easily identify which school he belongs to by
looking at his uniform. But if the boy swaps his sweater with a
friend from another school, the policemen will no longer be
able to recognise him and he can escape. This is how the
pneumococcus bacteria evade detection by the vaccine."

Dr Bowden and colleagues identified a number of recombined
serotypes that had managed to evade the vaccine. One in
particular grew in frequency and spread across the US from east
to west over several years. They also showed that during
recombination, the bacteria also traded a number of other parts
of the genome at the same time, a phenomenon never before
observed in natural populations of pneumococcus. This is of
particular concern as recombination involving multiple
fragments of DNA allows rapid simultaneous exchange of key
regions of the genome within the bug, potentially allowing it
to quickly develop antibiotic resistance.

The original 7-valent vaccine in the US has now been replaced
by a 13-valent vaccine, which targets thirteen different
serotypes, including the particular type which had escaped the
original vaccine. In the UK, the 7-valent vaccine resulted in a
substantial drop in disease overall. This overall effect was a
mixture of a large drop in frequency of the serotypes targeted
by the vaccine with some growth in serotypes not targeted by
the vaccine. The 13-valent vaccine was introduced in the UK in
2010.

Derrick Crook, Professor of Microbiology at the University of
Oxford and Infection Control Doctor at the Oxford University
Hospitals NHS Trust, adds: "Childhood vaccines are very
effective at reducing disease and death at a stage in our lives
when we are susceptible to serious infections. Understanding
what makes a vaccine successful and what can cause it to fail
is important. We should now be able to understand better what
happens when a pneumococcal vaccine is introduced into a new
population. Our work suggests that current strategies for
developing new vaccines are largely effective but may not have
long term effects that are as successful as hoped."

Dr Bernard Beall, a scientist at the Centers for Disease
Control and Prevention commented: "The current vaccine strategy
of targeting predominant pneumococcal serotypes is extremely
effective, however our observations indicate that the organism
will continue to adapt to this strategy with some measurable
success."

The Wellcome Trust, which part-funded this research, views
combating infectious disease and maximising the health benefits
of genetic research as two of its strategic priorities. Dr
Michael Dunn, Head of Molecular and Physiological Sciences at
the Wellcome Trust commented: "New technologies allow us to
rapidly sequence disease-causing organisms and see how they
evolve. Coupled with collaborations with epidemiologists, we
can then track how they spread and monitor the potential impact
this will have on vaccine efficiency. This will provide useful
lessons for vaccine implementation strategies."

###

[ |
E-mail
| Share

]

AAAS and EurekAlert! are not responsible for the accuracy
of news releases posted to EurekAlert! by contributing
institutions or for the use of any information through the
EurekAlert! system.

Go here to see the original:
Genetics study reveals how bacteria behind serious childhood disease evolve to evade vaccines

Comments are closed.