Pillar 1
Pathogen evolution and escape
Virus & immune response
Need
There is an urgent need to understand defects of immunity against SARS-CoV-2 in older adults, including its breadth across different antigens of the virus, clonal complexity, functional adequacy, durability, and the ability to guard against virus escape variants. The current pandemic presents a once-in-a-lifetime opportunity to address these needs and fill the gaps in knowledge, with the purpose to protect both adult and older populations from COVID-19.
Proposed Solution
Our studies of immunity and virus evolution will address critical fundamental and practical gaps in knowledge regarding immunity to SARS-COV-2, with special focus on older adults: How broad, diverse, durable, sensitive and functionally effective are the T and B cell response against SARS-CoV-2 in adult and older populations? How effective are they in preventing subsequent infections, and by what mechanisms? Is this effectiveness influenced by prior immunological encounters with endemic coronaviruses and how? Can we predict when another coronavirus epidemic will emerge based on immune response to SARS-CoV2 variants? And how broad, diverse, durable, sensitive and functionally effective/protective are the T and B cell response against SARS-CoV-2 vaccination in adult and older populations?
Statement of Work
Our group will perform three broad tasks: 1. Dissect duration, magnitude, sensitivity and functionality of primary and memory B and T cell responses against SARS-CoV-2 infection in adult and older populations and also test if these responses are influenced by prior coronavirus infections; 2. Characterize durability, magnitude, sensitivity and functionality of primary and memory B and T cell responses against SARS-CoV-2 vaccination in adult and older populations, and test if these responses are influenced by prior coronavirus infections; and 3. Connect receptor diversity and breadth of the adaptive response in adult and older populations to susceptibility to SARS-CoV-2 escape variants, allowing us to predict the propensity of new SARS-CoV-2 variants to cause new outbreaks and to engineer strategies to formulate new vaccines to protect general, as well as vulnerable, populations, including older adults.
