Humoral and cellular immune responses to COVID-19 infections and vaccinations in older and frail adults

Older adults have born the brunt of the COVID-19 pandemic. Despite their 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 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 9,000 samples that we have collected from the "COVID-19 in LTC" study. In this study, 1500 people from 26 different retirement communities and long-term care homes gave blood about every three months between March 2021-July 2023. Because we know what kinds of health conditions and medications people had, as well when people got infected, we can determine what kinds of immune responses protect from infection and which don't. We can also determine how health, age, sex, and frailty impact immune responses to vaccines and infection. 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 observed that some types of vaccines protect older adults better than others and we aim to find out why. This study is essential to protect our most vulnerable from ongoing COVID outbreaks and to design better vaccines against other current and new respiratory pathogens.