Respiratory Virus Immunity
Virus infections of the respiratory tract are responsible for a great deal of illness and mortality among the world's human population. Influenza, in particular, has a history of causing deadly pandemics and the continuing emergence of influenza around the world, including both the highly pathogenic H5 and recent H1N1 viruses, is reason for concern. It is essential to understand how the immune system controls virus infection and provides long term immunity if we are to design more rational vaccination and treatment strategies. The lab has a combined program in basic research using animal models of influenza infection and immunity, as well as a translational research program to study human immune responses.
Because productive influenza infection is typically restricted to the lung, immune control of the infection depends on both antibodies and T cells localized in the lung tissue and airways, with secondary contributions from memory T cells in the lymphoid organs. Therefore, a particular focus is to understand how T cells are regulated in the environment of the lung tissue and airways.
Our basic research program is focused on studying the function of adhesion molecules expressed by activated and memory T cells in the lung. The integrin Very Late Antigen-1 (VLA-1) is specific for collagen IV found primarily in basement membranes. Flu specific T cells can be found in close association with the basement membranes of the lung, and deletion of the VLA-1 alpha-1 integrin gene diminishes the ability of the T cells to be retained in the lung. One major aim in the lab is to understand how T cell migrate within the airway epithelium, find infected epithelial cells, and provide immunity.
The concepts and information we gather from the animal models are being directly translated into the human situation. To this end, the New York Influenza Center of Excellence (NYICE), a robust collaborative program for basic and translational investigation of influenza virology, pathogenesis, immunology, and vaccines has been established. Cutting-edge molecular tools will allow us to identify the virus-specific T cells and follow them over time in the study subjects. The information gathered will be informative for the next generation of flu vaccines.
- The use of self-adjuvanting nanofiber vaccines to elicit high-affinity B cell responses to peptide antigens without inflammation. Biomaterials. 34, 8776-85. (2013 Nov 01).
- CD4 T cell help is limiting and selective during the primary B cell response to influenza infection. J Virol. In press. (2013 Oct 23).
- Inflammation-induced interstitial migration of effector CD4⁺ T cells is dependent on integrin αV. Nat Immunol. 14, 949-58. (2013 Sep 01).