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Science
09 March 2025

Study Reveals Lasting Immune Memory From Shingles Vaccine

Research tracks CD4+ T cell responses one year post-vaccination, highlighting their roles and changes.

Recent research has shed light on the long-term effects of the recombinant zoster vaccine (RZV), particularly on the immunity of CD4+ T cells. This study examined how well these memory T cells, specific to glycoprotein E (gE) of the varicella zoster virus (VZV), respond over the course of one year following vaccination.

Understanding the dynamics of T cell immunity is especially pertinent for older adults, who face increased risks of developing shingles, also known as herpes zoster. The RZV vaccine has been shown to significantly diminish this risk, yet the mechanisms by which it induces durable immunity have not been fully elucidated.

The researchers, based at the Benaroya Research Institute at Virginia Mason, focused on participants who were at least 50 years old and had the relevant HLA haplotypes. Blood samples were collected multiple times: right before the first vaccine dose, and again at 14 days, 60 days, 74 days, and 365 days post-vaccination. Such longitudinal studies are imperative, as they provide insights not just on immediate immune responses but also on long-term protective effects.

Utilizing cutting-edge technology, the study employed tetramer-guided epitope mapping and single-cell RNA sequencing (scRNA-seq) to analyze the specific responses of T cells and observe their genetic activity. The findings revealed fascinating results: after one year, memory T cells specific to VZV gE persisted at elevated levels, and had activated markers indicating readiness to respond to infections.

One notable observation included the retention of specific T cell receptor (TCR) clonotypes over time. The authors noted, "memory T cells with the most dominant TCR clonotype pre-vaccination remain prevalent at year one post-vaccination." This recurrence suggests these dominant clonotypes are fundamental for maintaining the immune response, reinforcing their importance during re-exposure to the virus.

Upon analyzing transcriptional changes, the study concluded, "These data implicate a major role for pre-existing memory T cells in perpetuating immune repertoires upon re-encountering cognate antigens." This indicates not only survival but also potentially enhanced activation states and functional readiness of these T cells long after vaccination.

Further analysis revealed differential gene expression pre- and post-vaccination. T cells exhibited marked changes associated with activation and long-lasting functional states, providing possible pathways for future vaccine design. Such insights could lead to improved strategies for vaccination protocols aimed especially at the elderly population.

From this comprehensive study, it is clear the RZV vaccine does not merely trigger short-term responses; it bolsters the immune system’s memory, paving the way for sustained protection against shingles. This research emphasizes the significant role of committed memory T cells and their transcriptional adaptation post-vaccination, underscoring the need for continuous exploration of immune memory and functionality.

This work contributes meaningfully to our comprehension of how vaccines can mold the immune system and persist as effective safeguards against diseases, transforming our approach to vaccination, especially among vulnerable populations.