In a new study, researchers at La Jolla Institute for Immunology (LJI) show that one way to improve the body’s immune response to vaccines is to factor in antigen valency, which refers to the number of antibody binding sites on an antigen, according to a news release.
Scientists know a lot about how to design vaccines, but there are many diseases that have not been controlled through vaccination. HIV, for example, mutates quickly and is very good at hiding from the immune system, so it is hard for scientists to figure out which antigens to include in a vaccine, LJI said. For the new study, which is available online in Immunity, the researchers worked closely with the LJI Microscopy Core and used an advanced imaging technique called two-photon microscopy to visualize the effects of valencies on B cell responses.
The researchers discovered that high-valency antigens can lead the body to make more antibody-producing B cells. It is like the immune system sees the many targets on these antigens and takes a scatter-shot approach at hitting them. In fact, a valency of 60 seems to be enough to boost B cell numbers, and a valency of four might be enough in many cases. Low-valency antigens do lead to a smaller, more targeted B cell response. These B cells are rarer, but they are more likely to be sharp-shooters. These cells are said to have a “high affinity.”
Scientists have known about valency for a long time, but it had been hard to test which antigen valencies would work best in vaccines. A big problem is that different pathogens do not just differ in valency. They also have different structures, different modes of entering cells, and different strategies for evading the immune system. This means scientists studying the effects of valency are stuck comparing apples to oranges.
To solve this problem, the researchers teamed up with the Schief lab at Scripps Research. Schief and his colleagues had developed versions of an HIV protein with antigen valencies that ranged from one to 60. These antigens were all based on proteins from HIV, making them superior to engineered antigens used for previous valency studies. The LJI and Scripps Research teams then worked together to test the antigens in mice.
Valency will still be an important ingredient to consider in vaccine design. For example, because HIV is hard for the immune system to recognize, the B cells that target the virus are very rare. That means high-valency antigens could help boost those rare B cell populations by spurring a more-is-better immune system reaction. Scientists may also need to consider valency when designing COVID-19 vaccines. Different labs around the world are testing vaccines that contain antigens with many different valencies.
