Current influenza vaccines are considered safe and effective for the general population, but post-vaccination adverse events, including autoimmune manifestiations, have been described in previously healthy individuals. Although infections, including influenza, can trigger flares in patients with autoimmune diseases, whether or not to vaccinate these patients remains a subject of discussion. In adult patients with systemic lupus erythematosus (SLE), influenza vaccine has been reported to be safe for those with quiescent disease but is not recommended for patients with active disease. Vaccination is not considered to be a causal factor for SLE initiation, but a temporal association with flare-ups has been described and the subject is still a matter of debate. Our systems biology approach to study pediatric autoimmune diseases has permitted us to discover novel pathways that can be applied to the study of humoral immune responses in healthy individuals. We now propose to use the same approach to study the response to influenza vaccination in healthy children and children with systemic autoimmunity. We propose to focus on 1) three cellular compartments that are essential for the generation and the quality of antibody responses to vaccine, i) the inducers (dendritic cells);ii) the regulators (CD4-i-, including follicular helper T cells), and iii) the effectors (B cells);2) two diseases (SLE and JDM) where we have found alterations in these 3 compartments. The studies that we herein propose will address: 1) which are the best biomarkers of protective immune response to influenza vaccine in healthy children;2) how unique autoimmune backgrounds set the stage for responsiveness/unresponsiveness to vaccines;3) whether vaccination contributes to increase the breadth of autoimmunity in a disease-specific manner. Ultimately, we expect that these studies will shed light on basic aspects of humoral immune responses to vaccines and will permit us to discover biomarkers of response that can be applied to healthy children and to the general population.

Public Health Relevance

Current flu vaccines are considered safe and effective but post-vaccination adverse events, including autoimmune symptoms, have been reported in previously healthy individuals. We will study how the immune systems of healthy children and children who have either lupus or juvenile dermatomyocifis (two autoimmune diseases) respond to the flu vaccine. We expect to find markers that indicate a strong immune response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI089987-04
Application #
8501329
Study Section
Special Emphasis Panel (ZAI1-QV-I)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$423,289
Indirect Cost
$93,537
Name
Baylor Research Institute
Department
Type
DUNS #
145745022
City
Dallas
State
TX
Country
United States
Zip Code
75204
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

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