Glenn’s PhD research has focused on the study of immunosenescence, using HIV-infection as a model of accelerated immune aging. Since then, he has continued his pursuit on understanding the drivers of this aging phenomenon, and has focused on studying the impact of immunosenescence on vaccination in recent years. These studies are supported by cutting-edge flow cytometry and immune-profiling platforms.

Vaccination remains one of the most cost-effective public health strategies to alleviate the healthcare burden imposed by influenza, with the primary aim of preventing serious infections, complications, hospitalizations and death. While vaccination efficacy in the elderly remains poorly perceived, a growing number of reports describe high seroprotection rates (>90%) and comparable vaccination efficacy between the young and old in influenza vaccinated cohorts; this heterogeneity in vaccination outcomes suggest that multiple host factors (genetics, immune competency, antigen exposure, metabolic constitution etc.) play a role in dictating vaccination outcomes in the elderly. In an earlier report, we described a cohort of 205 influenza-vaccinated elderly adults who attained high seroprotection (>95%) and seroconversion (>80%) rates. Since we observed considerable variability in the seroconversion capacity of individuals for each vaccine strain, we attempted to identify parameters that were associated with strain responsiveness. We observed that bile acid profiles were distinct between those who responded to all influenza strains and those who did not; the latter also displayed a more senescent T-cell profile. On day 7 post-vaccination, elderly who responded to multiple influenza strains upregulated genes associated with B cell proliferation and immunoglobulin synthesis, DNA processing and editing, and the unfolded protein response (UPR). Behaviorally, those who responded better to vaccination were also more physically active. We conclude that interventions that target the unfolded protein response may be important for the generation of a multi-strain response in the trivalent influenza vaccination (TIV) of elderly individuals.