UGA researchers are working to develop a new generation of vaccines to protect against a variety of bacterial infections.
Fikri Avci, an assistant professor of biochemistry and molecular biology in the Franklin College of Arts and Sciences and a member of UGA’s Center for Molecular Medicine, is leading a project that will improve understanding of the fundamental molecular mechanisms involved in creating new vaccines that seek out carbohydrates found on the surface of pathogens.
His work, which is supported by a $1.2 million grant from the National Institutes of Health, may ultimately pave the way for vaccines that are more efficacious and easier to produce.
Carbohydrates, or glycans, adorn the surface of nearly every cell in the human body, but they are also found on bacteria, viruses and cancerous cells. The carbohydrates on different cells carry unique signatures, and the immune system can be trained to recognize and attack specific cell types based on these hallmarks.
“One of the problems in the field of carbohydrate vaccine research is that a lot of work is based on trial and error,” Avci said. “Scientists will identify a vaccine target and measure its protective capacity to conclude that it works or not.
“But we don’t have a good understanding of what is happening in between those steps,” he also said. “We have limited knowledge on how that vaccine interacts with and stimulates the immune system at the cellular and molecular level. This project will help us better understand many of these basic cellular processes and create vaccines that generate a stronger immune response.”
In a previous study, Avci and his colleagues identified a class of T cells that are able to recognize carbohydrates on the surface of cells. T cells are a kind of white blood cell that act as the core components of the highly specific and effective adaptive immune response against invading pathogens.
Avci will expand on his previous research into carbohydrate-specific T cells, which he calls Tcarbs, to define the molecular mechanisms for Tcarb activation in a model for Streptococcus pneumoniae, a bacterium that may cause pneumonia, meningitis or bloodstream infections.
For the T cells to recognize the correct carbohydrates, they must be presented to the T cells with an attached carrier-peptide, which then binds to a specialized protein called major histocompatibility complex class II, or MHCII. Like a molecular red flag, carbohydrates presented by MHCII alert T cells to the presence of a dangerous pathogen or cancerous cell, which they then begin to dismantle using the body’s immune response systems.
Avci already has tested this hypothesis by designing a new carbohydrate-based vaccine against a model of streptococcus that produced an immune response up to two orders of magnitude greater than existing vaccines.
Avci cautions that more work must be done at the molecular level before these techniques are used to create a vaccine for humans, but it may be possible to one day produce target-specific vaccines that are highly protective and produced at low cost using the mechanisms his lab is studying for the project.
