Increasing vaccine antibody durability

Vaccination is the most effective public health intervention, protecting us from infectious diseases and cancer. However, human variability in vaccine response leads to significant health inequalities. The individuals immunological status or 'immunotype'—impacted by genetic differences, age, past infections, and body weight—dictates this response and so the risk of severe disease. Focusing first on one aspect of this immunotype, weight, my research has made discoveries about vaccine failure in people with obesity. Poor maintenance of vaccine antibodies in people with obesity could be caused by dysregulated IL-6 signalling. I now propose to examine the impact of IL-6 signalling variability on vaccine responses in older people. Additionally, increasing the detail of our antibody maintenance studies through lymph node analysis and through mouse models of human variability. This research will then leverage the personalisation advantage of modified-mRNA therapeutics to develop specific strategies to overcome vaccine inequalities. We now create specific modified mRNA vaccines for genetic variants of pathogens or individual tumour mutations; similarly, my proposal will develop improved mRNA vaccine therapeutics by targeting deficiencies in individuals’ immunological characteristics. Given the growing proportion of the population that are older and living with obesity, this proposal addresses a vaccine-protection imbalance of increasing societal importance.