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.
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.
|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; García-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