Neeltje van Doremalen, Ph.D.

Our lab is dedicated to understanding the unique role of the mucosal immune system in protecting the respiratory tract against viral infections. Unlike the systemic immune system, the mucosal immune system acts as the first line of defense at critical surfaces such as the respiratory tract, gut, and reproductive organs. Key players in this defense include tissue-resident memory T cells and secretory IgA, which operate independently of systemic responses. We aim to unravel how mucosal immunity is induced and how it provides protection against respiratory viruses, particularly in the context of infections in the upper and lower respiratory tracts.

We investigate the immune responses elicited by respiratory viruses such as influenza A viruses and coronaviruses, focusing on both mucosal and systemic adaptive immunity. Using rodent models, we study the humoral and cellular responses elicited by different infection routes and analyze the role of innate immunity in shaping adaptive responses. By leveraging techniques like high dimensional flow cytometry, systems serology, deep mutational scanning, single-cell transcriptomics, and multiplex imaging, we gain spatial and temporal insights into immune responses across critical tissues, including the nasal-associated lymphoid tissue, nasal turbinates, lungs, and lymph nodes. These studies enable us to map mucosal immunity comprehensively and identify the breadth and depth required for protection upon rechallenge.

We additionally aim to identify correlates of protection and optimize vaccine strategies to induce robust mucosal immunity. We evaluate diverse vaccine platforms—including mRNA, vectored, and subunit vaccines—administered via various routes, such as intranasal, intramuscular, and inhalation. By comparing vaccine technologies and regimens, we aim to establish principles for designing universal vaccines capable of inducing broad, durable mucosal immune responses. Ultimately, our goal is to provide foundational insights that improve vaccine design and our understanding of protective mechanisms against respiratory viruses.

Immunohistochemistry staining of nasal-associated lymphoid tissues (NALT). The upper panels show CD3 (yellow, marking T cells) and PAX5 (teal, marking B cells). The lower panels depict Ki67 (purple, marking proliferating cells). Samples were collected at various time points following intranasal vaccination of mice with a replication-incompetent adenovirus vaccine. Acknowledgements: Reshma K. Mukesh, Carl Shaia, Jessy Prado-Smith.

Credit: NIAID

Immunohistochemistry staining of nasal turbinates and NALT tissues with CD3 (brown), highlighting the migration of T cells into these regions. Samples were collected at various time points after intranasal vaccination of mice with a replication-incompetent adenovirus vaccine. Acknowledgements: Reshma K. Mukesh, Carl Shaia, Jessy Prado-Smith.

Credit: NIAID