Division of Influenza



1. ID Pathogenicity and Transmissibility of Novel Influenza Viruses 

T.M. Tumpey

Seasonal epidemics and periodic pandemics are an ever-present international public health burden. During seasonal epidemics, the risk for hospitalization and death are highest among persons at either end of the age spectrum, as well as those with underlying medical conditions. During pandemic years the death rate is significantly higher. The factors that lead to the generation of pandemic viruses are complex and poorly understood, however the ability of a novel influenza virus to cause significant illness and transmit through the air are critical properties of pandemic influenza strains. The recurrent isolation of novel influenza viruses from humans raises public health concerns and highlights the need to better understand the potential of these viruses to spread and cause disease in humans. Current research of my group analyzes the virulence, transmissibility and growth properties of novel influenza viruses isolated from humans. Additional studies may determine the virus genes and how they act in concert to efficiently promote virulence and transmission in animal models. Knowing the inherent virulence and transmissibility of novel influenza viruses, relative to seasonal influenza viruses, is important for executing appropriate public health responses.


References

Maines TR, A. Jayaraman, J. A. Belser, D. Wadford, C. Pappas, H. Zeng, K. Gustin, M.B. Pearce, K. Viswanathan, Z. Shriver, R. Raman, N. Cox, R. Sasisekharan, J. M. Katz, and T. M. Tumpey. 2009. Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in ferrets and mice. Science 325:484-7. 

 

Maines TR, J. A. Belser, K. M. Gustin, N. van Hoeven, H. Zeng, N. Svitek, V. von Messling, J. M. Katz and T. M. Tumpey. 2012. Local Innate Immune Responses and Influenza Virus Transmission and Virulence in Ferrets. J Infect Dis. 205(3):474-85.


2. ID Modulating Host Innate and Adaptive Immune Responses to Enhance Disease Resistance and the Immunogenicity of Vaccines 

P. Sambhara 

Current research of my group falls broadly into three categories: (1) immunobiology of aging and improving the efficacy of influenza vaccines for the elderly; (2) host innate and adaptive immune responses to infections; (3) novel preventive and therapeutic strategies against pandemic influenza, including vaccine development. Opportunities exist utilizing state-of-the-art cellular, molecular, and biochemical technologies to study innate immunity, modulation of immune responses, antigen processing and presentation, B- and T-cell function and memory, and vaccine delivery systems.

References

Hoelscher, M., Garg, S., Bangari, D.S., Belser, J., Lu, X., Stephenson, I., Bright, R.A., Katz, J.M., Mittal, S.K., and Sambhara, S. (2006).  Development of adenoviral vector-based pandemic influenza vaccine against antigenically distinct human H5N1 strains in mice. Lancet, 367: 475.

Guo, G., Chen, L-M., Gomez, J.A., Fujita,T., Katz, J.M.,  Donis, R.O., and Sambhara, S.  (2007). NS1 protein of Influenza A Virus inhibits the function of intracytoplasmic pathogen sensor, RIG-I.  Am. J. Resp. Cell Mol. Biol. 36:236.

Sambhara, S., and Poland, G.A. (2007). Breaking the Immunogenicity barrier of bird flu vaccines. Lancet,  370:544.

Plowden, J., Hoelscher, M., Gangappa, S., Engleman, C., Katz, J.M., and Sambhara, S. (2004). Impaired antigen-induced CD8+ T cell clonal expansion in aging is due to defects in antigen presenting cell function. Cell. Immunol. 229:86.  


3. ID Investigation of Novel Prophylactic and Therapeutic Strategies for Seasonal and Pandemic Strains of Influenza Viruses.  

S. Gangappa 

The main focus of research activities of my group is to improve protective immunity to influenza infection through; a) discovery of novel broad spectrum antiviral agents and b) identification of immune deficits and improve influenza vaccine efficacy in the immunocompromised hosts. Opportunities for prospective research fellows/trainees include in vitro (cell culture), in vivo (murine models), and clinical studies (vaccine trials) addressing protective immunity to seasonal and pandemic strains of influenza viruses using up to date cellular immunology and molecular assays to delineate immune mechanisms underlying novel class of broad spectrum anti-virals and vaccines. 
 

References  

Szretter KJ, Gangappa S, Lu X, Smith C, Shieh WJ, Zaki SR, Sambhara S, Tumpey TM, Katz JM. 2007. Role of host cytokine responses in the pathogenesis of avian H5N1 influenza viruses in mice. J. Virol. 81 (6): 2736-44. 

Mueller SN, Matloubian M, Clemens DM, Sharpe AH, Freeman GJ, Gangappa S, Larsen CP, Ahmed R. 2007. Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection.Proc Natl Acad Sci. 104(39):15430-5. 

Gangappa S, Kokko KE, Carlson LM, Gourley T, Newell KA, Pearson TC, Ahmed R, Larsen CP. 2008. Immune responsiveness and protective immunity after transplantation. Transpl Int. 1-24 

Stapler D, Lee ED, Selvaraj SA, Evans AG, Kean LS, Speck SH, Larsen CP, Gangappa S. 2008. Expansion of Effector Memory TCR V{beta}4+CD8+ T Cells Is Associated with Latent Infection-Mediated Resistance to Transplantation Tolerance. J Immunol. 180(5):3190-200

 

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