UBC scientists study how vaccines work
A pair of physician-researchers at the University of B.C. are taking part in a global “deep dive” into the mechanisms that make vaccines work, hoping to gain insights that could lead to vaccines for HIV, tuberculosis and malaria.
Vaccines provide effective protection to billions of people against a long list of diseases, but the trouble is that doctors and scientists aren’t sure why.
Because they don’t know exactly what to look for, Tobias Kollmann and Manish Sadarangani will watch for changes in thousands of unique proteins and molecules, DNA and even the body’s resident colonies of fungi and bacteria.
“Vaccines are a very difficult thing to study because there are reactions taking place all over the body,” said Kollmann, the interim head of the division of infectious diseases in the department of pediatrics at UBC. “You can’t put this in a petri dish and get the same results.”
When a vaccine enters the body, the human machinery produces specialized antibodies, biological beat cops that detect and destroy one specific virus or bacterium, often for the entire life of the recipient.
“Almost everything in between is a black box,” said Kollmann. That knowledge gap makes it difficult to improve existing vaccines and to develop new ones, particularly for stubborn problems such as HIV, tuberculosis and malaria, which have no effective vaccine.
Kollmann and Sadarangani were selected for the investigation by the Human Vaccines Project, a worldwide consortium of vaccine experts similar to the Human Genome Project.
A dozen volunteers will provide blood and tissue samples from their lymph nodes before inoculation, and then again at specific intervals after each of three hepatitis B vaccine injections. Then the researchers will look for every response and biological signature they can.
“By taking a systems biology approach we are trying to capture all the changes and responses that we can in an agnostic way,” said Kollmann.
That is because you never know what might turn out to be important.
Recently, researchers were surprised to learn that the immune response to the influenza vaccine is greatly enhanced by the presence of certain bacteria in the gut.
“The influenza vaccine has nothing to do with these little bacteria, so this was flabbergasting and at first it was completely disregarded, because no one thought (the bacteria) could ever be important,” said Kollmann. “It’s really important to accept that we don’t know what we don’t know and to look at everything.”
Subsequent animal research revealed that without the bacteria, there is no immune response to the influenza vaccine, which also turned out to be true of a handful of other vaccines, he said. A molecule from the bacteria can be added to flu shots to ensure their effectiveness.
The researchers are especially interested in what’s going on inside “super-responders,” people who get full protection after a single dose, said Sadarangani, director of the Vaccine Evaluation Centre.
Most people require three doses to ensure lifetime protection from hepatitis B.
“We are really interested in what’s happening after the first dose in that one-third of people who have an immediate immune response that is not happening in the other two-thirds,” he said. “We would like to know how to get that response in everyone.”
Once the project identifies biological signals associated with antibody production, they can start more focused research to build a clear picture of the chain of cause and effect that triggers antibody production and, hopefully, identify new approaches to vaccine development.
“The ideal vaccine is a single dose that you can give to anyone, anytime that leads to lifelong protection,” said Kollmann. “That’s what the Human Vaccines Project is after.”
We are trying to capture all the changes and responses that we can in an agnostic way.