A new immunity study has found a way to improve the body’s immune response to vaccines by factoring in antigen valency, or the number of antibody binding sites on an antigen, according to researchers from the La Jolla Institute and Scripps Research.

According to the study authors, with a higher antigen valency, antibodies have more sites to latch onto; however, including a higher antigen valency in a vaccine does not mean it will work better.

“Different vaccines have vastly different valencies. Diphtheria toxin is a dimer, valency of 2. Hepatitis B vaccine is 100–120,” said study author Yu Kato, PhD, in a press release. “There is no clear consensus as to how the differing valencies impact B cell responses since these antigens also differ in many other ways.”

In the study, the researchers used an advanced imaging technique called 2 photon microscopy to visualize the effects of valencies on B cell responses. The research team found that high-valency antigens can lead the body to make more antibody-producing B cells, claiming that a valency of 60 is enough to boost B cell numbers and a valency of 4 might be enough in other cases.

The researchers said that low-valency antigens do lead to a smaller, more targeted B cell response. These B cells are rarer but are more likely to be sharp-shooters and have a “high affinity,” according to the study authors.

One challenge the researchers faced is that different pathogens do not just differ in valency; they differ in structures, differing modes of entering cells, and differing strategies for evading the immune system.

To solve this issue, the research team had developed versions of an HIV protein with antigen valencies that ranged from 1 to 60. The antigens were based on proteins from HIV, making them superior to engineered antigens used for previous valency studies.

The researchers concluded that although vaccines need a valency of more than 1 binding site, choosing a valency of 4 over a valency of 60 does not have a big effect on B cell responses. However, valency will still be an important ingredient to consider in vaccine design.

Since HIV is hard for the immune system to recognize, the B cells that target the virus are very rare, meaning the high-valency antigens could help boost those rare B cell populations by spurring a more-is-better immune system reaction, according to the study authors.

Selecting antigens with the right valency will really depend on the disease scientists are trying to target. In addition, the scientists may need to consider valency when designing coronavirus disease 2019 vaccines.

REFERENCE
Beating HIV and COVID-19 may depend on tweaking vaccine molecules. La Jolla Institute. https://www.lji.org/news-events/news/post/beating-hiv-and-covid-19-may-depend-on-tweaking-vaccine-molecules/. Published August 27, 2020. Accessed September 2, 2020.