As a geriatrician interested in the promotion of health and prevention of disability, the work in my laboratory has focused on developing methods for measuring key components of cell-mediated immunologic defense mechanisms against influenza illness. By understanding how the immune system changes with age in its response to influenza virus and increases the risk for serious morbidity and mortality in older people, we can develop new strategies for enhanced prophylaxis against influenza and potentially other acute respiratory illnesses in this population.

The long-range goal of this project is to use translational methodology to determine the mechanism by which age and disease-related factors increase the risk of influenza and diminish vaccine efficacy. The objective is to characterize protective immunologic responses, compare the level of immunity in different risk groups, and finally define the level of laboratory measures of the T-cell response that predict outcomes of illness in older people. These assays of T-cell responses could then be applied to testing the effectiveness of new vaccines or other immunoenhancing agents in the prevention or treatment of other infectious, neoplastic or degenerative disorders in older adults.

The specific projects in the laboratory are:

Measurement of the immune response to influenza vaccination in ex vivo cultures of peripheral blood mononuclear cell cultures stimulated with influenza virus. Granzyme B is produced in cytotoxic T lymphocytes and is a key mediator of cytolytic activity against virus-infected cells. Different assays for levels of granzyme B are being developed.

Determine the effect of chronic diseases on the levels of different cytokines and cytolytic mediators, and whether or not people develop influenza illness in spite of having been vaccinated. Healthy young and older people are compared to those with congestive heart failure.

Study age-related changes in the expression of Toll-like receptors in response to influenza and whether or not pathogen-derived molecules that stimulate TLR can be used as adjuvants to improve immune responsiveness to influenza vaccination in older people.

Clinical trials and basic research in the efficacy and underlying mechanisms of a proprietary ginseng extract for the prevention of acute respiratory illness in older people.

McElhaney JE, Pinkoski MJ, Upshaw C, Bleackley RC: The cell-mediated cytotoxic response to influenza vaccination using an assay for granzyme B activity. J Immunol Methods, 190:11-26, 1996.

Powers DC, McElhaney JE, Florendo Jr. OA, Manning MC, Upshaw CM, Bentley DW, Wilkinson BE: Humoral and cellular immune responses following vaccination with purified recombinant hemagglutinin from influenza A (H3N2) virus. J Infect Dis, 175:342-351, 1997.

McElhaney JE, Gravenstein S, Upshaw CM, Hooton JW, Krause P, Drinka P: Immune response to influenza vaccination in institutionalized elderly: Effect on different T-cell subsets. Vaccine, 16(4): 403-409, 1998.

McElhaney JE, Gravenstein S, Upshaw C, Hooton J, Krause P, Drinka P, Bleackley RC: Granzyme B response to influenza vaccination: a marker of risk for influenza in institutionalized older adults. Vaccine 19:3744-51, 2001.

Letter C, Gravenstein S, McElhaney JE. Influenza Vaccination Is Less Effective For Stimulating A Granzyme B Response In Older Adults. Elsevier Science B.V. International Congress Series, 1219:713-721, 2001.

Ewen C, Kane KP, Shostak I, Griebel PJ, Bertram EM, Watts TH, Bleackley RC, McElhaney JE. A novel cytotoxicity assay to evaluate antigen-specific CTL responses using a colorimetric substrate for Granzyme B. J Immunol Methods 276:89-101, 2003.

McElhaney JE, Gravenstein S, Cole SK, Davidson E, O'Neill D, Petitjean S, Rumble B, Shan JJ. A placebo-controlled trial of a proprietary extract of North American ginseng (CVT-E002) to prevent acute respiratory illness in institutionalized older adults. J Am Geriatr Soc 52(1):13-9, 2004.

McElhaney JE, Herre JM, Cole SK, Hooton JW. Effect of congestive heart failure on humoral and cellular immune responses to influenza vaccination. Vaccine 22(5-6):682-9, 2004.