Investigate the role of parenteral vaccine-trained tissue-resident macrophages in host defense against heterologous bacterial infections

Immunological memory has traditionally been solely attributed to T and B lymphocytes in the adaptive immune system. Recently, the concept of immunological memory has been expanded to include innate immune memory, which can be defined as an altered state of the innate immune system after primary exposure to an antigen or microbe that will modify its responsiveness to the same or different antigen/microbe. Trained innate immunity (TII), a subset of innate immune memory, is characterized by cellular and epigenetic changes, along with protection against heterologous infections. Ample evidence of TII induced by systemic administration of certain vaccines exists. However, there are many knowledge gaps about the capacity of systemic vaccination to invoke TII in local tissue-resident cells. Given the recent and widespread human vaccination with mRNA-based and viral-vector-based SARS-CoV2 vaccines, it is of great relevance to study whether these vaccines are capable of inducing TII in local tissue-resident cells. This project will employ a murine model to examine the capacity of parenteral delivery of mRNA-based and viral-vector-based vaccines to induce TII in respiratory-mucosal tissue-resident macrophages, and the mechanisms underlying any observed training. Secondly, the project will seek to determine if TII invoked by these vaccines will lead to protection against heterologous bacterial infections and if so, how this protection is attained. In the recent climate of the COVID-19 pandemic, with mass global vaccinations and rapidly evolving variants that may evade current vaccines, it is of high importance to investigate the potential of SARS-CoV2 vaccines to evoke TII. Furthermore, future vaccination strategies would benefit greatly to evoke both innate and adaptive immunity.