The primary goal of this project is to use differences in the human response to a single vaccine antigen to determine factors that are critical to the ability of an individual to make a protective response to the vaccine. The vaccine antigen used in these studies is the major surface antigen of Hepatitis B virus, HBsAg. Using a broad range of tools, including genome-wide transcriptional profiling, multiparameter flow cytometry and detailed functional phenotyping of antigen-specific T cell subset, we will determine which components of the innate and adaptive response to vaccine correlate best with the seroprotective response to vaccination. The major part of this project will be a systems biology study of the same antigen, HBsAg, with two different adjuvants. Alum and the Toll-like receptor-9 agonist, CpG-ODN. Clinical trials have shown CpG-ODN to be a much more effective vaccine, especially in subjects that respond poorly to vaccination due age or disease. We propose to compare transcriptional and cellular responses to these two adjuvants in older healthy adults and later in patients with end-stage renal disease of HIV infection. This study presents a unique opportunity to study in humans the mechanisms of action of the most widely used adjuvant, alum and one of the most promising modern adjuvant candidates, CpG-ODN, in a study in which the adjuvants are the only significant variable. These studies will constitute an important advance in our understanding of the actions of adjuvants and will hopefully identify the primary reasons for unresponsiveness to vaccination in older adults and in specific disease states.

Public Health Relevance

Many adults respond poorly to vaccination because of old age or disease. As a result, many of the people most in need of vaccination are not effectively protected. New vaccine adjuvants offer promise for improving results in these difficult to immunize groups, but the way they work is not understood. The goal of this project is to provide a clear understanding of how vaccine adjuvants work in poorly responding individuals and to suggest new strategies to develop improved vaccines for these groups.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-QV-I)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor Research Institute
United States
Zip Code
Heinonen, Santtu; Jartti, Tuomas; Garcia, Carla et al. (2016) Rhinovirus Detection in Symptomatic and Asymptomatic Children: Value of Host Transcriptome Analysis. Am J Respir Crit Care Med 193:772-82
Schmitt, Nathalie; Liu, Yang; Bentebibel, Salah-Eddine et al. (2016) Molecular Mechanisms Regulating T Helper 1 versus T Follicular Helper Cell Differentiation in Humans. Cell Rep 16:1082-95
Bentebibel, Salah-Eddine; Khurana, Surender; Schmitt, Nathalie et al. (2016) ICOS(+)PD-1(+)CXCR3(+) T follicular helper cells contribute to the generation of high-avidity antibodies following influenza vaccination. Sci Rep 6:26494
de Steenhuijsen Piters, Wouter A A; Heinonen, Santtu; Hasrat, Raiza et al. (2016) Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection. Am J Respir Crit Care Med 194:1104-1115
Blohmke, Christoph J; Darton, Thomas C; Jones, Claire et al. (2016) Interferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever. J Exp Med 213:1061-77
Sandoval, Carmen; Barrera, Aldo; Ferrés, Marcela et al. (2016) Infection in Health Personnel with High and Low Levels of Exposure in a Hospital Setting during the H1N1 2009 Influenza A Pandemic. PLoS One 11:e0147271
Ueno, Hideki; Banchereau, Jacques; Vinuesa, Carola G (2015) Pathophysiology of T follicular helper cells in humans and mice. Nat Immunol 16:142-52
Schmitt, Nathalie; Ueno, Hideki (2015) Regulation of human helper T cell subset differentiation by cytokines. Curr Opin Immunol 34:130-6
Turner, Jacob A; Bolen, Christopher R; Blankenship, Derek M (2015) Quantitative gene set analysis generalized for repeated measures, confounder adjustment, and continuous covariates. BMC Bioinformatics 16:272
Zitvogel, Laurence; Galluzzi, Lorenzo; Viaud, Sophie et al. (2015) Cancer and the gut microbiota: an unexpected link. Sci Transl Med 7:271ps1

Showing the most recent 10 out of 54 publications