Humoral and cellular immune responses to COVID-19 vaccination and infection in older adults.

Older adults have born the brunt of the COVID-19 pandemic. Despite having high vaccination rates, they are still the most likely to become infected, hospitalized, and die of COVID-19. Although it is tempting to see this as a failure of our current vaccines, the COVID-19 mRNA vaccines far outperformed vaccines for influenza or pneumonia in reducing infections and deaths in older adults. We have learned a lot about the types of immune responses these vaccines generate but, surprisingly, we still don't really understand why some older and frail adults are protected while others are not. Studies from other types of vaccines find that the immune responses that protect younger adults are not necessarily the same as those that protect older adults. We aim to figure this out using over 10,000 samples that we have collected from the "COVID-19 in LTC study". In this study we had over 1000 people from 26 different retirement homes and long-term care homes give blood about every three months between March 2021-December 2023. Because we know what kinds of health conditions and medications people had, as well when people got infected, we can uncover the role of medications and health conditions and determine what kinds of immune responses protect from infection and which don't. One of the aims of this proposal is to investigate different types of antibodies including antibodies that stimulate immune cells to kill virus infected cells, antibodies that stop the virus from getting into cells, and antibodies that are thought to lead to less inflammatory immune responses. Because we know who did and did not get infected, we can investigate which of these are protective. We have also discovered some counter-intuitive findings where instead of protecting people from infections, sometimes having an omicron infection makes them more likely to get another infection. We need to understand why this is so we can prevent infections and tailor vaccine schedules to protect our most vulnerable.