| Summary: | Vaccines are one of the greatest medical triumphs. Due to the empirical nature of vaccine development, however, it is still unclear how we maintain immunological memory and protection following vaccination. Using cells from a cohort of healthy infants and the hepatitis B virus (HBV) vaccine as a model, I developed a vaccine-specific stimulation assay that detects multiple immune readouts simultaneously from memory T cells in response to antigen stimulation in vitro. By stratifying my cohort by their anti-HBV surface antigen antibody (anti-HBs) titers, I determined how their HBV-specific memory T cell immune responses differed stratified by serological response. Based on my results, interferon (IFN)-γ appeared to be the most consistent predictor of a stronger serological response to HBV vaccination. The most striking trend was a positive correlation between bulk IFN-γ secretion and anti-HBs titers at 6 and 18 months following vaccination. A similar trend was noted for interleukin (IL)-10 secretion, but it did not extend past the 6-month time point. Tumor necrosis factor (TNF)-α, on the other hand, had a dynamic production profile. Overall, TNF-α production in proliferating CD8 T cells was increased in those subjects who produced lower levels of anti-HBs six months after vaccination. This observation was reversed by the 18-month time point—children who had anti-HBs titers less than 10 IU/l secreted lower levels of TNF-α. Many poor responders, as defined by their anti-HBs titers, demonstrated evidence of T cell memory either by HBsAg-specific proliferation, intracellular cytokine production, or cytokine secretion—indicating that an alternative or additional immunological mechanism might also correlate with vaccine-induced protection. The ultimate goal of this research project was to develop an in vitro antigen stimulation protocol that minimized sample usage and gathered data to help generate hypotheses regarding how the adaptive immune system, as a whole, responds to vaccination. The results from my study identified IFN-γ, TNF-α, as well as IL-10 as potential targets for continued investigation. However, in order to determine which immune parameters—whether humoral, cell-mediated, or even innate immunity—best predict strong and long-lasting immunological memory, we need to design more comprehensive longitudinal studies that extend beyond infancy.
|
|---|
