A major challenge in vaccinology is that the efficacy of a vaccine can only be ascertained retrospectively, upon infection. The identification of molecular signatures induced rapidly after vaccination which correlate with and predict, the later development of protective immunity, would represent a strategy to prospectively determine vaccine efficacy. Such a strategy would be particularly useful when evaluating the efficacy or immunogenicity of untested vaccines, or in identifying individuals with sub-optimal responses amongst high risk populations such as the elderly. We have recently used a systems biology approach to identify early gene signatures that predict later immune responses in humans vaccinated with the yellow fever vaccine YF- 17D. The goal of the present application is to determine extent to which such an approach will have broad utility in predicting the immunogenicity of other vaccines, and in identifying new correlates of protective immunity. To achieve this goal we have initiated a highly collaborative effort to perform a comprehensive analysis of immune responses induced by three distinct vaccines: (i) the inactivated trivalent influenza vaccine, (ii) the pneumococcal polysaccharide vaccine and (iii) the live attenuated varicella-zoster vaccine. These three vaccines were selected for this study because influenza virus, pneumococcus and zoster, 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 immunity 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. The program is organized into two Research Projects: 1. Innate signatures (Pulendran), and 2. Adaptive Immunity (Ahmed). These will be supported by an Adminstrative Core (Pulendran), a Clinical Core (Mulligan), an Epitope Mapping Core (Sette), and a Computational Core (Haining). The successful completion of this program may provide insights into the defects that underlie poor vaccine efficacy in the elderly, and establish the broad utility of systems biology in predicting vaccine immunogenicity.
Our recent work with the yellow fever vaccine demonstrates that systems biology approaches provide a new and unbiased way to probe the immune response to vaccination in humans, and discover molecular signatures that can predict vaccine induced immunity. In the present proposal, we seek to determine whether such an approach is generally applicable to different types of vaccines in the young and elderly populations.
|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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