Gene behind vaccine 'memory' revealed
Last Updated: Monday, November 9, 2009 | 9:05 AM ET
Australian Broadcasting Corporation
Scientists have pinpointed the gene responsible for how the body responds to vaccines, a discovery that could lead to better vaccinations.
The research, published in Monday's edition of Nature Immunology, shows that when this gene is mutated the body "forgets" it's ever been vaccinated.
Clinical immunologist Dr. Katrina Randall of the Canberra Hospital said the findings could improve treatment of transplant rejection, autoimmunity and allergy.
She said past research has demonstrated that immunization saves lives, but the direct mechanisms behind its success have remained unclear until now.
And there are some people who have problems developing a proper response to vaccines, she said.
To further understand this, the research team conducted studies on genetically mutated mice models.
Randall said mice models are often used to study human diseases.
"We were investigating these mice and we found they had a very good response to their first vaccination and were making antibodies," she said.
But when the mice were re-examined a few weeks later, Randall said, no antibodies were found.
"It was like they hadn't had the original vaccination," said Randall.
Randall said that because the genetic mutations in the mouse models were random, they had to search for the specific gene responsible for the malfunctioning antibodies.
After carrying out association studies to find the precise genetic region involved, the team found a mutation in the gene Dock8 was causing the problem.
"We then wanted to look at the functional consequences of the mutation," said Randall.
In normal mice, she said, the vaccine would interact with specialized white blood cells called B cells to create antibodies.
Over time, these antibodies build up to form a protective army should the mice ever be infected by the target pathogen, said Randall.
'Memory' of immunization
"Immunity normally lasts for years after we are immunized or infected because our immune system remembers the shape and 'fingerprints' of an infecting microbe and keeps making antibodies against them," she said.
Randall said the interaction between the B cells and the vaccine occurs at the B cell synapse.
"The synapse is any point of contact between two cells," said Randall.
But Randall said a mutation in the Dock8 gene stops this interaction from taking place.
Randall and her team believe without this interaction the B cells die before they've had a chance to become long-lived memory B cells.
"If the synapse isn't formed properly then the cells die out before they've had a chance to make the long-lived antibodies and before they've been able to make the memory B cells that circulate to give you long term immunity," said Randall.
Randall said this work could lead to better treatment of people whose bodies are unable to produce an immune response to vaccinations. It could also help scientists develop better vaccines.
A paper published in the New England Journal of Medicine earlier this year found people with a mutation in Dock8 are more susceptible to infections, she said.
The research will now focus on how Dock8 works in humans, said Randall.
