One of the most feared diseases in the world is making an alarming comeback in
the UK. Cases of tuberculosis increased by 10 per cent in 2005, with 8,494
cases, and are set to continue rising, as the bug becomes increasingly
resistant to drugs, and international travel extends its global reach.
TB kills about 1.6 million people a year, largely in developing countries, and
experts believe that its global resurgence goes hand in hand with the Aids
pandemic. However, Helen McShane, a British scientist, announced today that
a groundbreaking new vaccine – the first in 80 years, which has taken ten
years to develop – is being tested in human clinical trials for the first
time.
The areas most affected by the disease in Britain are cities such as London,
Birmingham and Leicester, with immigrant communities from areas where the
disease is still common: Pakistan, Bangladesh and parts of Africa. One in
five cases of TB is found in new arrivals into the country. However, the
disease is not something you could simply catch on a train; only frequent or
prolonged contact with someone with TB puts a person at risk (hence why it’s
passed within families), and it can be treated with antibiotics if diagnosed
quickly.
Nevertheless, the Government is so concerned at the growing number of people
with TB that it is considering screening visitors to the UK from countries
such as China and India, it was revealed this week.
If the new TB vaccine passes its trials, as it is expected to do, it could be
available in your GP’s practice by 2015, when it would work as a booster for
the childhood BCG injection (now given only to children in high-risk
groups), conferring long-lasting immunity on all adults and thus preventing
the spread of this disease.
Symptoms include a persistent cough, weight loss and fever. Before the First
World War there were more than 100,000 UK cases a year, but numbers have
fallen steadily since the BCG vaccination was introduced in 1953.
Dr McShane, the scientist behind this latest booster vaccine, is a 40-year-old
medical doctor-turned-vaccinologist. It’s impossible not to share her
excitement, particularly when she describes the day in her Oxford University
laboratory when she realised she was on to something.
“It was a little tense,” says Dr McShane, who was then 35 and five years into
a project that she had started as a PhD student in 1997. “I went into the
lab to check blood tests taken the day before, looked at the plates and
couldn’t believe my eyes. The results were excellent. We knew the vaccine
would stimulate the production of some antibodies but there were ten times
the number we had predicted. I ran down the corridor to show my professor
immediately.”
Dr McShane knew she had created a vaccine that could potentially save two
million lives a year worldwide. The Wellcome Trust will today announce her
project as the first new vaccine for TB in 80 years.
There are two main reasons why a new vaccine has taken so long to develop. The
first is that it’s a difficult bug to vaccinate against as it disguises
itself efficiently in the body. There are different strains of the bug, but
Dr McShane believes that they are similar enough for the vaccine to be
effective against them all. The other reason for the delay, according to the
charity TB Alert, is that there wasn’t any funding. Until recently TB was
prevalent only in the developing world and so drug companies were reluctant
to plough money into a vaccine.
A potential vaccine is an achievement that Dr McShane would not have dared to
imagine when she first joined Professor Adrian Hill at the Nuffield
Department of Medicine in Oxford to begin a PhD. “Most students were working
on a malaria project; no one was looking at a TB vaccine, so I thought it
would be a good idea,” she says.
Dr McShane had first started to study the tuberculosis bacterium when, as a
young doctor, she was working in an HIV clinic in London. The two diseases
often present hand-in-hand because TB is an oppor-tunistic infection and
finds the weakened immune system of an HIV-infected person an easy way in.
Dr McShane says she found it frustrating that she could offer the latest
antiret-rovirals for the HIV infection but she had nothing to prescribe
except traditional antibiotics for the TB. She could see that as different
strains of TB bacteria became resistant to these drugs, her armoury was
looking more and more depleted. Surely something could be done?
She decided to take her curiosity into the laboratory. Most contagious
diseases can be vaccinated against by priming the immune system to recognise
the pathogen and building armies of immune cells to attack it if it invades
the body. A vaccine against measles, for example, introduces a highly
weakened strain of the disease into the body. This allows the immune system
to target the responsible bacteria, deal with them, and prepare defences for
attacks in the future.
But TB is more complicated as it is able to hide inside cells and avoid normal
antibodies. Instead it requires a subgroup of white blood cells, called T
cells, to be activated, which are better at seeking out the bug to destroy
it.
Immunologists have begun to use recombinant viruses to teach the body how to
recognise TB bacteria and prepare its T cells correspondingly. These are
modified viruses that carry cloned genes containing a simple protein,
harvested from the disease to be fought. The “tweaked” virus is harmless to
human beings. It arrives in the body, unloads the cloned protein, and dies.
The protein, however, is spotted by the immune system, which prepares T
cells for attack. Afterwards, the patient’s body is left ready for further
invasion.
Dr McShane found that her vaccine worked particularly well at boosting the
weak immune response primed by the traditional BCG.
“It would be fantastic if this vaccine was proven to work and became
available,” she says. “It’s been a huge team effort with units in The Gambia
and South Africa and Oxford working to a common end. The real challenges now
are to see if it really does stop people getting TB, and if it does, to make
sure that it gets to the people who need it.”
For further information on tuberculosis, log on to www.tbalert.org
Heart vaccine: blocking childhood viruses
A childhood vaccine against heart disease, available in ten years’ time: this
is the ambitious assignment of Professor Vijay Kakkar (pictured), the
director of the Thrombosis Research Institute and emeritus professor at the
University of London.
Cardiovascular disease is one of the world’s most common killers, but its
causes are not entirely understood. Lifestyle factors play a part, as do
genetics. However, infection by bacteria or certain viruses may also cause
changes in blood vessels that create localised hardening of the arteries.
This happens early on, usually at around age 2 or 3. Professor Kakkar, 70,
has been studying changes in blood vessels caused by infection and
subscribes to the theory that long-term build-up in these hardened areas may
lead to atherosclerosis (furring of the arteries) and its accompanying risk
of heart attack and stroke.
He believes that a vaccine that blocks the childhood infections that trigger
atherosclerosis could prevent the initial damage and thus prevent the
disease occurring. His team, based in London, Bangalore and Hungary, has
been developing an antibody that is capable of identifying pathogens that
could cause infection and inflammation.
Early trials are under way and Professor Kakkar says “it has been progressing
well so far”. But will it be ready for use by 2015? “It has to be, otherwise
I will retire,” he says.
Malaria vaccine: fighting a changing parasite
The immunologist Dr Richard Pleass (pictured) and his team at the University
of Nottingham had a double goal, a vaccine that can cure malaria and protect
against its recurrence.
Dr Pleass, 40, proposes to use naturally occuring antibodies as the basis of a
vaccine, harvested from a group of people in The Gambia that are naturally
immune to the disease. He discovered that these people’s antibodies provide
immunity from the parasite, and if he can find a way to deliver copies of
them safely to people, it would treat the infection on the spot and protect
from subsequent bouts.
The work is vital; malaria is becoming resistant to existing preventive drugs,
which leaves many relying on preventive measure such as bed-nets soaked in
pesticides.
Finding a vaccine is difficult because the parasite constantly changes its
“appearance” – the proteins on its surface. This means that the body’s
immune defences do not recognise it from one time to the next. Therefore,
unlike diseases that always look the same and so usually infect people only
once, such as mumps, people repeatedly get infected with malaria. However,
Dr Pleass found that the Gambians had antibodies to a part of the parasite
that never changed, and so their immune system recognised it every time it
invaded the body.
“It has been hellish hard work,” says Dr Pleass, who began the project in
Dundee in 1998 with a Wellcome Trust Fellowship. “We need to make enough
antibodies to begin a small trial in human beings but they are expensive. So
we spend hours worrying about grants or applying for them.”
