Vaccines represent the major success of immunology and have spared countless numbers of people from infections. Despite their success, we understand little about how effective vaccines stimulate protective immune responses. Three classes of vaccine can be distinguished: i) highly effective vaccines such as yellow fever, measles and smallpox;ii) good vaccines which yield protective immunity in a majority of people including seasonal Influenza (Flu) vaccines, hepatitis B and pneumovax;and iii) vaccines which are largely not effective at the current time including HIV-AIDS, malaria, and Hepatitis C. We surmise that understanding the modus operandi of good vaccines in healthy people and understanding their shortcomings by studying hypo-responsive people will permit us to unravel the immunological principles of vaccination. Two recent developments promise to yield such understanding: i) the appreciation of the crucial role of dendritic cells in inducing and tuning the immune responses and ii) advances in high-throughput molecular profiling technologies underlying systems biology approaches. We hypothesize that a systems biology analysis will yield a comprehensive view of the immune alterations associated with a potent response to flu vaccination. We further hypothesize that efficient vaccination is associated to the early activation of antigenpresenting cells. Our goal is to identify early biomarkers of effective antibody responses to flu vaccination.
Four aims are proposed to meet this goal:
Aim 1 : To establish the baseline immune profiles in healthy subjects.
Aim 2 : To establish the immune profiles of Flu vaccination in healthy subjects.
Aim 3 : To identify the molecular signatures of DC subset(s) in response to Flu vaccination.
Aim 4 : To identify the molecular signatures of activated monocytes in response to Flu vaccination.

Public Health Relevance

Despite the success of vaccines, we understand little about how effective ones stimulate protective immune responses. We will study how the flu vaccine generates effective antibody responses. The goal is to identify the immune responses elicited by effective vaccines so that vaccines that aren't as effective can be improved. To do this, we will vaccinate healthy people with the flu vaccine and monitor their immune response following the vaccination.

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 #
8501325
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
$491,578
Indirect Cost
$108,626
Name
Baylor Research Institute
Department
Type
DUNS #
145745022
City
Dallas
State
TX
Country
United States
Zip Code
75204
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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