
Personalised vaccines could protect all children
07 December 2009 by Charlotte King
Magazine issue 2737. Subscribe and get 4 free issues.
For similar stories, visit the Epidemics and Pandemics and Genetics Topic Guides
CHILDREN whose genetic make-up means they may not be protected by the standard form of a vaccine could in future be given a personalised shot. This is the prospect raised by the discovery of gene variants that seem to predict whether an individual will produce enough antibodies in response to a vaccine to protect them against disease.
Vaccines expose the immune system to a deactivated version of a disease agent. This prompts the production of specific antibodies, which will bind to the real disease-causing agent if the vaccinated person is later exposed to it. Though all of us usually get the same vaccines in the same doses, not everyone produces enough disease-specific antibodies in response. As a result, between 5 and 20 per cent of people vaccinated against hepatitis B, and between 2 and 10 per cent of those vaccinated against measles, will not be protected if they ever encounter these viruses.
Various factors determine who goes unprotected, but it is clear that genes play a major role. Finding out which gene variants lead to an abnormally weak vaccine response could allow people with these variants to be given alternative immunisations. These might take the form of higher doses of the standard vaccine, or a modified version of it.
To work out which genes help determine the immune response to common childhood vaccines, Berran Yucesoy of the US National Institute for Occupational Safety and Health in Morgantown, West Virginia, and her colleagues focused on genes that code for cytokines. These cell-signalling molecules help to produce antibodies and recruit infection-fighting cells.
Yucesoy's team analysed the DNA of 141 healthy babies aged between 11.5 and 14 months, searching for variations in 11 cytokine genes. They then gave the babies routine vaccines for hepatitis B and pneumococcus and a standard diphtheria-tetanus-whooping cough combination vaccine, and measured the levels of antibodies in their blood.
When the team analysed their results, they found single-letter variations in seven of the cytokine genes that were more common in infants who produced low levels of antibodies in response to certain vaccines. Most variants were associated with antibodies to just one disease, although in one case, the same variant was associated with fewer antibodies to tetanus and more to pneumococcus (Vaccine, DOI: 1016/j.vaccine.2009.09.076).
The researchers still have to confirm their results in a larger population of children, and to demonstrate that these gene variants translate into a lack of disease protection. But if the results stand up, infants' genes could be routinely screened for these variants before vaccination. If a child has some of the variants, the missing cytokines could be added to the vaccine formulation. Another option would be to add immune stimulants or give a higher dose of vaccine, to increase the response from the intact cytokine genes.
"Although the findings of the paper need confirming, it is possible that, in future, knowledge of an individual's genetic background might allow doctors to use vaccinations especially designed to get the optimum response for someone with that particular genetic background," says Hilary Longhurst, an immunologist at St Bartholomew's Hospital in London.
07 December 2009 by Charlotte King
Magazine issue 2737. Subscribe and get 4 free issues.
For similar stories, visit the Epidemics and Pandemics and Genetics Topic Guides
CHILDREN whose genetic make-up means they may not be protected by the standard form of a vaccine could in future be given a personalised shot. This is the prospect raised by the discovery of gene variants that seem to predict whether an individual will produce enough antibodies in response to a vaccine to protect them against disease.
Vaccines expose the immune system to a deactivated version of a disease agent. This prompts the production of specific antibodies, which will bind to the real disease-causing agent if the vaccinated person is later exposed to it. Though all of us usually get the same vaccines in the same doses, not everyone produces enough disease-specific antibodies in response. As a result, between 5 and 20 per cent of people vaccinated against hepatitis B, and between 2 and 10 per cent of those vaccinated against measles, will not be protected if they ever encounter these viruses.
Various factors determine who goes unprotected, but it is clear that genes play a major role. Finding out which gene variants lead to an abnormally weak vaccine response could allow people with these variants to be given alternative immunisations. These might take the form of higher doses of the standard vaccine, or a modified version of it.
To work out which genes help determine the immune response to common childhood vaccines, Berran Yucesoy of the US National Institute for Occupational Safety and Health in Morgantown, West Virginia, and her colleagues focused on genes that code for cytokines. These cell-signalling molecules help to produce antibodies and recruit infection-fighting cells.
Yucesoy's team analysed the DNA of 141 healthy babies aged between 11.5 and 14 months, searching for variations in 11 cytokine genes. They then gave the babies routine vaccines for hepatitis B and pneumococcus and a standard diphtheria-tetanus-whooping cough combination vaccine, and measured the levels of antibodies in their blood.
When the team analysed their results, they found single-letter variations in seven of the cytokine genes that were more common in infants who produced low levels of antibodies in response to certain vaccines. Most variants were associated with antibodies to just one disease, although in one case, the same variant was associated with fewer antibodies to tetanus and more to pneumococcus (Vaccine, DOI: 1016/j.vaccine.2009.09.076).
The researchers still have to confirm their results in a larger population of children, and to demonstrate that these gene variants translate into a lack of disease protection. But if the results stand up, infants' genes could be routinely screened for these variants before vaccination. If a child has some of the variants, the missing cytokines could be added to the vaccine formulation. Another option would be to add immune stimulants or give a higher dose of vaccine, to increase the response from the intact cytokine genes.
"Although the findings of the paper need confirming, it is possible that, in future, knowledge of an individual's genetic background might allow doctors to use vaccinations especially designed to get the optimum response for someone with that particular genetic background," says Hilary Longhurst, an immunologist at St Bartholomew's Hospital in London.
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