Vaccines represent the major success of immunology and have spared countless numbers of people from infections. Despite this success, we understand little about how effective vaccines stimulate protective immune responses. We surmise that understanding the modus operandi of vaccines in healthy people and understanding their shortcomings by studying hypo-responsive people will permit us to unravel the immunological principles of vaccination. Three vaccines will be studied in great detail: inactivated influenza vaccine and hepatitis B vaccine with either alum as the traditional adjuvant (Engerix) or with CPGoligonucleotide (Heplisav). We surmise that systems biology approaches will permit us to gain a comprehensive view of the immunobiology associated with a potent response to vaccination. This will lead to the identification of biomarker signatures indicative of the quality of vaccine-induced antibody responses. This, in turn, will facilitate the rational design and development of novel improved vaccines. Our preliminary studies performed with 24 healthy volunteers indicate that three commercially available vaccines: Fluzone (influenza), Pneumovax and Engerix alter the blood cell composition and transcriptome in completely different ways. These preliminary results support our proposed strategy. They demonstrate that the different vaccines, which are able to induce protective humoral responses, mobilize different immune effectors. We propose five highly integrated projects which will be supported by seven cores. Our key deliverables will include: i) Increased knowledge on vaccine-induced immune system alterations in dendritic cells, monocytes and T follicular helper cells;ii) Biomarkers of humoral immune responses;iii) An ex vivo assay for prediction of immune response to vaccination;iv) Tools to assess vaccine-activated cells;v) A systems biology analysis of two adjuvants: Alum and CPG-Oligonucleotides;vi) A systems biology analysis of the response to vaccine in patients with altered immune systems;and vii) An Immunochip, or focused microarray, for the assessment of vaccine immune efficacy.

Public Health Relevance

Vaccines represent the major success of immunology and yet we understand little about how effective vaccines stimulate protective immune responses. Our preliminary studies indicate that three commercially available vaccines alter the blood cell composition and transcriptome in completely different ways to induce protective immunity. We propose five highly integrated projects supported by seven cores to characterize vaccine-induced immune system alterations using a systems biology approach.

National Institute of Health (NIH)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Johnson, David R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor Research Institute
United States
Zip Code
Yu, Chun I; Becker, Christian; Metang, Patrick et al. (2014) Human CD141+ dendritic cells induce CD4+ T cells to produce type 2 cytokines. J Immunol 193:4335-43
Banchereau, Romain; Baldwin, Nicole; Cepika, Alma-Martina et al. (2014) Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines. Nat Commun 5:5283
Chaussabel, Damien; Baldwin, Nicole (2014) Democratizing systems immunology with modular transcriptional repertoire analyses. Nat Rev Immunol 14:271-80
Rajsbaum, Ricardo; Garcia-Sastre, Adolfo; Versteeg, Gijs A (2014) TRIMmunity: the roles of the TRIM E3-ubiquitin ligase family in innate antiviral immunity. J Mol Biol 426:1265-84
Cao, Raquel G; Suarez, Nicolas M; Obermoser, Gerlinde et al. (2014) Differences in antibody responses between trivalent inactivated influenza vaccine and live attenuated influenza vaccine correlate with the kinetics and magnitude of interferon signaling in children. J Infect Dis 210:224-33
Schotsaert, Michael; GarcĂ­a-Sastre, Adolfo (2014) Influenza vaccines: a moving interdisciplinary field. Viruses 6:3809-26
Alsina, Laia; Israelsson, Elisabeth; Altman, Matthew C et al. (2014) A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4. Nat Immunol 15:1134-42
Ovsyannikova, Inna G; White, Sarah J; Albrecht, Randy A et al. (2014) Turkey versus guinea pig red blood cells: hemagglutination differences alter hemagglutination inhibition responses against influenza A/H1N1. Viral Immunol 27:174-8
Li, Lily; Lin, Marvin; Krassilnikova, Maria et al. (2014) Effect of cholecalciferol supplementation on inflammation and cellular alloimmunity in hemodialysis patients: data from a randomized controlled pilot trial. PLoS One 9:e109998
Tsang, John S; Schwartzberg, Pamela L; Kotliarov, Yuri et al. (2014) Global analyses of human immune variation reveal baseline predictors of postvaccination responses. Cell 157:499-513

Showing the most recent 10 out of 33 publications