Viral infections remain a considerable cause of morbidity and mortality. Despite advances in the availability of vaccines, the mechanisms of generating and maintaining effective antiviral immunity remains incompletely understood. A major concern in this regard is influenza virus, a focal point for a number of Projects in this Program. The vaccine for influenza virus must be remade each year because it has not yet been possible to generate broadly protective immunity to this rapidly evolving RNA virus and the potential emergence of devastating pandemic influenza virus strains remains ever present. Thus, it is essential that we understand the basic principles of long-term B cell and T cell immunity to viral infections, including influenza virus, to improve existing, and develop novel, vaccination strategies. A major complication with influenza virus infection is co-infection with bacteria resulting in bacterial pneumonia. It is unclear how such a co-infection with a virus and bacterial pathogen in the respiratory tract impacts antiviral immunological memory and future protective immunity to the virus. To address these questions, the research Projects will utilize common infectious agents. The overall goal of Core B is to generate, standardize, store and provide infectious agents to the Projects. In addition, Core B will optimize and validate assays to monitor the burden of infectious agents in tissues from infected animals. Thus, the specific Aims for this core are: 1) To define a model of respiratory infection with Streptococcus pneumonia (Sp) and coinfection with Sp and influenza virus;2) To generate and characterize Streptococcus pneumoniae expressing CD4 T cell determinant(s) from influenza virus HA;and 3) To produce, standardize, maintain and store infectious agents. The activities of this Core will therefore create synergy and interaction between the different Projects by creating a common and easily accessible set of tools, and by enhancing the quality, standardization and reproducibility of the data generated by the individual Projects.

Public Health Relevance

Influenza virus remains a major human pathogen and the threat of the emergence of pandemic strains remains ever present. In addition, a major complication during influenza virus infection is co-infection with respiratory bacterial infections. To investigate the mechanisms of immunity to influenza virus and to begin to understand the immunological impact of co-infection, Core B will provide infectious agents to the Projects.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-BDP-I)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
United States
Zip Code
Kurachi, Makoto; Barnitz, R Anthony; Yosef, Nir et al. (2014) The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells. Nat Immunol 15:373-83
Schadler, Keri L; Crosby, Erika J; Zhou, Alice Yao et al. (2014) Immunosurveillance by antiangiogenesis: tumor growth arrest by T cell-derived thrombospondin-1. Cancer Res 74:2171-81
Wolf, Amaya I; Strauman, Maura C; Mozdzanowska, Krystyna et al. (2014) Pneumolysin expression by streptococcus pneumoniae protects colonized mice from influenza virus-induced disease. Virology 462-463:254-65
Richard, Aimee L; Siegel, Steven J; Erikson, Jan et al. (2014) TLR2 signaling decreases transmission of Streptococcus pneumoniae by limiting bacterial shedding in an infant mouse Influenza A co-infection model. PLoS Pathog 10:e1004339
Crawford, Alison; Angelosanto, Jill M; Kao, Charlly et al. (2014) Molecular and transcriptional basis of CD4? T cell dysfunction during chronic infection. Immunity 40:289-302
Wolf, Amaya I; Strauman, Maura C; Mozdzanowska, Krystyna et al. (2014) Coinfection with Streptococcus pneumoniae modulates the B cell response to influenza virus. J Virol 88:11995-2005
Farber, Donna L; Yudanin, Naomi A; Restifo, Nicholas P (2014) Human memory T cells: generation, compartmentalization and homeostasis. Nat Rev Immunol 14:24-35
Weissler, Katherine A; Caton, Andrew J (2014) The role of T-cell receptor recognition of peptide:MHC complexes in the formation and activity of Foxp3? regulatory T cells. Immunol Rev 259:11-22
Crosby, Erika J; Goldschmidt, Michael H; Wherry, E John et al. (2014) Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection. PLoS Pathog 10:e1003970
Turner, Damian L; Gordon, Claire L; Farber, Donna L (2014) Tissue-resident T cells, in situ immunity and transplantation. Immunol Rev 258:150-66

Showing the most recent 10 out of 37 publications