Improving vaccination strategies and understanding and treatment of infectious diseases require identification and quantification of variables that determine the ability of the immune system to respond to an antigenic challenge. A particular challenge is the aging immune system where the ability to mount adaptive immune responses to vaccinations and viral infections declines. Variables that determine the outcome of an immune response and are sensitive to aging include the repertoire of antigen-specific T and B cells;the robustness of homeostatic control mechanisms;the ability of cells to migrate to the site of antigen exposure;the activation threshold of responding cell population;the availability of and responsiveness to nonspecific stimuli;and the ability of responding T and B cell population to proliferate and differentiate. We will perform immune profiling before and after VZV vaccination to identify signatures that correlate with successful T and B cell vaccine responses. The overreaching hypothesis is that comparison of vaccinated individuals of different age groups and patients with zoster reactivation will allow defining underlying mechanisms that can be used to target interventions to compensate for defective pathways.
In Specific Aim 1, we will perform a twin study to examine the influence of age and inherited factors on frequency, phenotype and repertoire of VZV-specific T cells in naturally acquired VZV immunity.
Specific Aims 2 and 3 propose a longitudinal study of the VZV vaccine response in different age groups.
Specific aim 2 will focus on the early immune response to define the factors that correlate with a rapid and diverse T cell response.
Specific Aim 3 proposes to identify T cell signatures at peak response that correlate with T cell memory development and antibody production.
In Specific Aim 4, we identify patients with zoster reactivation in two at-risk groups, patients with the autoimmune diseases rheumatoid arthritis and systemic lupus erythematosus and patients older than 60 years. Signatures obtained in these patients during active herpes zoster infection will be compared to the vaccination-induced signatures.

Public Health Relevance

With increasing age, vaccine responses decline, and vaccinations are only partially protective or not protective at all. A decrease in vaccination success rates is already evident in the 6th and 7thdecade of life. In addition, vaccinations with live viruses are associated with increased side effects. With the changing demographics of the US population, this decline in immune competence is a major health problem. An understanding of the immune aging process is necessary to improve the strategies whom and when to vaccinate and to identify means to improve vaccine responses in the elderly.

National Institute of Health (NIH)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
United States
Zip Code
Qi, Qian; Liu, Yi; Cheng, Yong et al. (2014) Diversity and clonal selection in the human T-cell repertoire. Proc Natl Acad Sci U S A 111:13139-44
Chang, Serena; Kohrt, Holbrook; Maecker, Holden T (2014) Monitoring the immune competence of cancer patients to predict outcome. Cancer Immunol Immunother 63:713-9
Qi, Qian; Zhang, David W; Weyand, Cornelia M et al. (2014) Mechanisms shaping the naïve T cell repertoire in the elderly - thymic involution or peripheral homeostatic proliferation? Exp Gerontol 54:71-4
Shekhar, Karthik; Brodin, Petter; Davis, Mark M et al. (2014) Automatic Classification of Cellular Expression by Nonlinear Stochastic Embedding (ACCENSE). Proc Natl Acad Sci U S A 111:202-7
Jackson, Katherine J L; Liu, Yi; Roskin, Krishna M et al. (2014) Human responses to influenza vaccination show seroconversion signatures and convergent antibody rearrangements. Cell Host Microbe 16:105-14
Lu, Yuan; Welsh, John P; Swartz, James R (2014) Production and stabilization of the trimeric influenza hemagglutinin stem domain for potentially broadly protective influenza vaccines. Proc Natl Acad Sci U S A 111:125-30
Wang, Chen; Liu, Yi; Xu, Lan T et al. (2014) Effects of aging, cytomegalovirus infection, and EBV infection on human B cell repertoires. J Immunol 192:603-11
O'Gorman, William E; Huang, Huang; Wei, Yu-Ling et al. (2014) The Split Virus Influenza Vaccine rapidly activates immune cells through Fc? receptors. Vaccine 32:5989-97
Rosenberg-Hasson, Yael; Hansmann, Leo; Liedtke, Michaela et al. (2014) Effects of serum and plasma matrices on multiplex immunoassays. Immunol Res 58:224-33
Kay, Alexander W; Fukuyama, Julia; Aziz, Natali et al. (2014) Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy. Proc Natl Acad Sci U S A 111:14506-11

Showing the most recent 10 out of 40 publications