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.
|Ho, Irvin Y; Bunker, Jeffrey J; Erickson, Steven A et al. (2016) Refined protocol for generating monoclonal antibodies from single human and murine B cells. J Immunol Methods 438:67-70|
|Nakaya, Helder I; Clutterbuck, Elizabeth; Kazmin, Dmitri et al. (2016) Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood. Proc Natl Acad Sci U S A 113:1853-8|
|Quicke, Kendra M; Bowen, James R; Johnson, Erica L et al. (2016) Zika Virus Infects Human Placental Macrophages. Cell Host Microbe 20:83-90|
|Godec, Jernej; Tan, Yan; Liberzon, Arthur et al. (2016) Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation. Immunity 44:194-206|
|Li, Shuzhao; Todor, Andrei; Luo, Ruiyan (2016) Blood transcriptomics and metabolomics for personalized medicine. Comput Struct Biotechnol J 14:1-7|
|Ravindran, Rajesh; Loebbermann, Jens; Nakaya, Helder I et al. (2016) The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation. Nature 531:523-7|
|Peng, Hesen; Ma, Junjie; Bai, Yun et al. (2015) MeDiA: Mean Distance Association and Its Applications in Nonlinear Gene Set Analysis. PLoS One 10:e0124620|
|Wang, Kai; Zhao, Qing; Lu, Jianwei et al. (2015) K-Profiles: A Nonlinear Clustering Method for Pattern Detection in High Dimensional Data. Biomed Res Int 2015:918954|
|Cobey, Sarah; Wilson, Patrick; Matsen 4th, Frederick A (2015) The evolution within us. Philos Trans R Soc Lond B Biol Sci 370:|
|Pulendran, Bali; Maddur, Mohan S (2015) Innate immune sensing and response to influenza. Curr Top Microbiol Immunol 386:23-71|
Showing the most recent 10 out of 74 publications