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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-QV-I)
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Baylor Research Institute
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Cepika, Alma-Martina; Banchereau, Romain; Segura, Elodie et al. (2017) A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis. J Exp Med 214:3449-3466
Athale, Shruti; Banchereau, Romain; Thompson-Snipes, LuAnn et al. (2017) Influenza vaccines differentially regulate the interferon response in human dendritic cell subsets. Sci Transl Med 9:
Schotsaert, Michael; García-Sastre, Adolfo (2017) Inactivated influenza virus vaccines: the future of TIV and QIV. Curr Opin Virol 23:102-106
Silvin, Aymeric; Yu, Chun I; Lahaye, Xavier et al. (2017) Constitutive resistance to viral infection in human CD141+ dendritic cells. Sci Immunol 2:
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
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
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
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 16:1082-1095
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
Suarez, Nicolas M; Bunsow, Eleonora; Falsey, Ann R et al. (2015) Superiority of transcriptional profiling over procalcitonin for distinguishing bacterial from viral lower respiratory tract infections in hospitalized adults. J Infect Dis 212:213-22

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