In an article published last month in Nature Communications, Benaroya Research Institute (BRI) scientists, Drs. Xiaomin Wen, Scott Presnell, and Alex Hu, led by Dr. Bill Kwok, found that pre-existing CD4 memory T cells that recognize the virus that causes shingles play a major role in strengthening the immune response upon re-exposure to antigen via vaccination. In addition, they found that the administration of the SHINGRIX™ vaccine produces a durable state among these CD4 memory T cells that may be the reason for this vaccine’s high efficacy.
Most adults over the age of 50 were exposed to the varicella-zoster virus (VZV) early in life when they contracted chickenpox. In adulthood, VZV can be reactivated in nerve cells and cause the painful rash known as shingles. The SHINGRIX™ vaccine prevents shingles by re-exposing the immune system to a noninfectious form of VZV, which strengthens the immune system’s response to the virus and keeps it suppressed. However, the mechanism of why this particular vaccine is so effective and what role CD4 T cells play has not been well understood.
BRI researchers hypothesized that memory T cells might play an important role in the vaccine’s effectiveness. Memory T cells are long-lived immune cells that retain memory of an antigen so that they can reactivate quickly and mount an immune response to pathogens if they encounter them again. Dr. Kwok and team conducted a year-long study in which adults received 2 doses of the SHINGRIX™ vaccine in order to investigate the roll of memory T cells upon antigen re-exposure. Using a unique technology invented at BRI by Dr. Kwok, known as a tetramer activation assay, Dr. Kwok’s team determined the frequency and phenotype of activated T cells specific for the VZV antigen before and after vaccination. The vaccine activated and expanded memory T cells from the original chickenpox infection and produced long-term memory. However, the gene expression of memory T cells pre-vaccination were distinct from those at one-year post-vaccination. This suggests that re-exposure to the VZV antigen via vaccination causes memory T cells to function differently. Ultimately, Kwok’s team believes these results point to the idea that VZV-specific CD4 memory T cells pre-vaccination play an important role in the immune response to the vaccine.
“Not only are the CD4 memory T cells reactivated, but they are also changing their gene expression so that they function differently, which suggests that their change in function contributes to the high efficacy of SHINGRIX™,” commented Dr. Kwok.
These insights may help scientists improve the efficacy of other multi-dose vaccines that rely on reactivating CD4 memory T cells, whose effectiveness wanes over time and requires booster shots. Improving vaccine efficacy may provide longer lasting protective immune responses.
For more information about BRI, visit www.benaroyaresearch.org.
