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 immune responses, 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 infants or the elderly. We and others have recently used a systems biology approach to identify early gene signatures that correlate with, and predict the later immune responses in humans vaccinated with the live attenuated yellow fever vaccine YFV-17D. Despite this promising advance, the extent to which such approaches can reveal the immunological mechanisms of action of vaccines, and help discover new correlates of protective immunity, remains untested. Furthermore, the potential public health impact of these strategies in predicting the immunogenicity, or even efficacy, of vaccines that induce sub-optimal responses in immunocompromised populations such as the elderly, needs to be rigorously evaluated. Within this context, the aims of the present grant are:
Aim 1 : Systems biological approaches to identify molecular signatures that predict the sub-optimal immunogenicity of the herpes zoster vaccine, a pneumococcal polysaccharide vaccine (PPV23), and the trivalent inactivated influenza vaccine (TIV) Aim 2: Systems biological analysis of transcriptional and micro RNA networks in dendritic cells from young versus elderly, stimulated in vitro with the herpes zoster vaccine, PPV23 and TIV.
Aim 3 : Systems biological analysis of innate responses during herpes zoster re-activation, and during acute infections caused by Streptococcus pneumoniae The successful completion of these aims will: (i) address important public health concerns regarding impaired immunogenicity of these vaccines in the elderly (ii) provide biological insight into novel innate correlates of immunity, and (iii) represent the first comprehensive evaluation of immune responses to any vaccine in the elderly versus young.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
4U19AI090023-02
Application #
8319085
Study Section
Special Emphasis Panel (ZAI1-QV-I (M2))
Project Start
2010-07-12
Project End
2015-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
2
Fiscal Year
2011
Total Cost
$739,512
Indirect Cost
Name
Emory University
Department
Type
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Yu, Tianwei (2018) Nonlinear variable selection with continuous outcome: a fully nonparametric incremental forward stagewise approach. Stat Anal Data Min 11:188-197
Levin, Myron J; Cai, Guang-Yun; Lee, Katherine S et al. (2018) Varicella-Zoster Virus DNA in Blood After Administration of Herpes Zoster Vaccine. J Infect Dis 217:1055-1059
Hagan, Thomas; Pulendran, Bali (2018) 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 10:
Kang, Hyun Min; Subramaniam, Meena; Targ, Sasha et al. (2018) Multiplexed droplet single-cell RNA-sequencing using natural genetic variation. Nat Biotechnol 36:89-94
Lopez, Romain; Regier, Jeffrey; Cole, Michael B et al. (2018) Deep generative modeling for single-cell transcriptomics. Nat Methods 15:1053-1058
Levin, Myron J; Kroehl, Miranda E; Johnson, Michael J et al. (2018) Th1 memory differentiates recombinant from live herpes zoster vaccines. J Clin Invest 128:4429-4440
Upadhyay, Amit A; Kauffman, Robert C; Wolabaugh, Amber N et al. (2018) BALDR: a computational pipeline for paired heavy and light chain immunoglobulin reconstruction in single-cell RNA-seq data. Genome Med 10:20
Bowen, James R; Zimmerman, Matthew G; Suthar, Mehul S (2018) Taking the defensive: Immune control of Zika virus infection. Virus Res 254:21-26
Woodruff, Matthew Charles; Kim, Eui Ho; Luo, Wei et al. (2018) B Cell Competition for Restricted T Cell Help Suppresses Rare-Epitope Responses. Cell Rep 25:321-327.e3
Yu, Tianwei (2018) A new dynamic correlation algorithm reveals novel functional aspects in single cell and bulk RNA-seq data. PLoS Comput Biol 14:e1006391

Showing the most recent 10 out of 105 publications