The overarching goal of this proposal is to use a systems biology approach to define innate signatures that can predict vaccine efficacy and immunogenicity in young adults and the elderly. To achieve this goal we have initiated a highly collaborative effort to perform a detailed cellular and molecular characterization of human immune responses induced by three distinct vaccines: (i) the T-dependent inactivated trivalent influenza vaccine ( TIV ), (ii) the T-independent pneumococcal polysaccharide vaccine 23 ( PPV23 ) and (iii) the live attenuated varicella-zoster vaccine ( zoster). These three vaccines were selected for this study because influenza virus, pneumococcus and VZV, are of global public health importance and the cause of severe morbidity and mortality, especially in the elderly and other high-risk groups . In addition, all three of these vaccines are known to generate sub-optimal immune responses in a substantial proportion of elderly vaccinees. Defining the innate signatures in these sub-optimal responders may provide insight into the defects that underlie poor vaccine efficacy and immunogenicity in the elderly. This information may form the basis for developing rational strategies to enhance vaccine efficacy in the aged population. The goal of Project #2 is to characterize the key adaptive immune responses for each vaccine in the young and elderly cohorts. These data will then be used by the Genomics and Computational Biology Core to identify the innate signatures (Project #1) that predict the various adaptive immune parameters that are measured in Project #2. The following specific aims are proposed to achieve our goals:
Aim 1 : To characterize the adaptive immune responses induced by TIV vaccination in the young and the elderly.
Aim 2 : To characterize the magnitude and quality of the B cell mediated adaptive immune responses to pneumococcal vaccination in the young and the elderly.
Aim 3 : To characterize the adaptive immune responses in the young and elderly after zoster vaccination.
These studies will provide insight into adaptive immune responses in the young and the elderly induced by VZV, influenza, and pneumococcal vaccines. These three vaccine are of public health importance and elicit poor responses in the elderly.
|Sinclair, Charles; Bommakanti, Gayathri; Gardinassi, Luiz et al. (2017) mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation. Science 357:1014-1021|
|Bergmann, Tobias; Lindvall, Mikaela; Moore, Erin et al. (2017) Peptide-binding motifs of two common equine class I MHC molecules in Thoroughbred horses. Immunogenetics 69:351-358|
|Hagan, Thomas; Pulendran, Bali (2017) Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? From Data to Understanding through Systems Biology. Cold Spring Harb Perspect Biol :|
|Kazmin, Dmitri; Nakaya, Helder I; Lee, Eva K et al. (2017) Systems analysis of protective immune responses to RTS,S malaria vaccination in humans. Proc Natl Acad Sci U S A 114:2425-2430|
|Weinberg, Adriana; Canniff, Jennifer; Rouphael, Nadine et al. (2017) Varicella-Zoster Virus-Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults. J Immunol 199:604-612|
|Bowen, James R; Zimmerman, Matthew G; Suthar, Mehul S (2017) Taking the defensive: Immune control of Zika virus infection. Virus Res :|
|Li, Shuzhao; Sullivan, Nicole L; Rouphael, Nadine et al. (2017) Metabolic Phenotypes of Response to Vaccination in Humans. Cell 169:862-877.e17|
|Ajami, Nassim E; Gupta, Shakti; Maurya, Mano R et al. (2017) Systems biology analysis of longitudinal functional response of endothelial cells to shear stress. Proc Natl Acad Sci U S A 114:10990-10995|
|Quicke, Kendra M; Diamond, Michael S; Suthar, Mehul S (2017) Negative regulators of the RIG-I-like receptor signaling pathway. Eur J Immunol 47:615-628|
|Mukund, Kavitha; Subramaniam, Shankar (2017) Co-expression Network Approach Reveals Functional Similarities among Diseases Affecting Human Skeletal Muscle. Front Physiol 8:980|
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