Khor, Bernard MD

PROJECT NARRATIVE People with Down syndrome exhibit advanced immune aging and have reduced response to influenza immunization compared to people without Down syndrome. Here, we propose a clinical trial to test whether high-dose influenza vaccine (Fluzone), already standard of care for people over the age of 65, is safe and effective to improve response to immunization in people with Down syndrome who are less than 65 years old. Our study will improve scientific understanding of the basis of reduced immune response in Down syndrome; if the trial is positive, high dose immunization is a rapidly actionable public health approach to improve respiratory health in this population.

The proposed research is relevant to public health because it interrogates how immune aging impairs functional response to vaccination and how dysregulation of CD4+ T cells drives advanced immune aging, leveraging Down syndrome as a genetic model. This knowledge would establish the foundation to identify the patients, both with and without Down syndrome, who would benefit from altered vaccination strategies, and novel therapeutics to attenuate advanced immune aging, with likely utility across a broad spectrum of immune- related conditions. Thus, the proposed research is relevant to the part of NIH’s mission pertaining to reducing illness and disability.

The proposed research is relevant to public health because it interrogates mechanisms of CD4+ T cell dysregulation and of impaired vaccine response in people with Down syndrome. This knowledge would establish the foundation to identify therapies to mitigate immune aging and impaired vaccine response in people, both with and without Down syndrome, with likely utility across a broad spectrum of immune-related conditions. Thus, the proposed research is relevant to the part of NIH's mission pertaining to reducing illness and disability.