September 30, 2015
A new study on the immune system's response to the influenza virus, tested in an animal model, presents a more complicated picture of how the body processes the infection, potentially signaling a new approach to the design of flu vaccines.
Led by CHOP scientist Laurence C. Eisenlohr, the study produced results that challenge the current model's assumption that antigens—substances that prompt an immune response—spread the infection primarily by way of external introduction to cells.
What Eisnlohr and his team found in their study, published this week in the journal Nature Medicine, is that deep endogenous cell processes spurred by live influenza are essential to the body's defense against its most infectious agents. Viral proteins taken up by antigen-presenting cells (APC) were specifically found to have more dynamic pathways inside the cell, where they get processed into peptides that activate protective CD4+ T cells.
“During infection, viral proteins are present throughout the cell, not just in the limited compartments that have been the focus of attention in classical immunology,” said Eisenlohr, a viral immunologist in CHOP's Department of Pathology and Laboratory Medicine. “By investigating how active infections interact with mechanisms deep inside immune cells, we can design vaccines with broader protection against invading pathogens.”
The study argues that the most robust antiviral response is stimulated by live vaccines rather than inactivated vaccines. If safety concerns are a factor in avoiding the use of live vaccines, it may be necessary to find ways to induce the response brought on by natural infection.
"We may need to modify inert vaccines to better mimic natural infection—accessing a broader variety of peptides and thus generating a more protective immune response,” Eiesnlohr said.
The study, supported by grants from the National Institutes of Health, calls for the consideration of revised strategies in vaccine design that account for unique properties in each pathogen.
