Influenza causes significant morbidity and mortality in hematopoietic cell transplantation (HCT) recipients, who are immunocompromised. Vaccination is the most effective way of preventing influenza but is less effective in immunocompromised patients than in healthy individuals. Thus, there is a need to understand the mechanisms underlying poor vaccine responses as well as establish biomarkers of immune competence. We surmise that understanding the relationships between antigen presenting cells (including monocytes and DCs), influenza-specific CD4+ T cells and antibody responses elicited by vaccination may enable a more rational design of vaccination strategies and timing in this group of patients. All studies to date have shown diminished CD4+ T cell numbers and proliferative T cell responses even at 12 months post transplant. We will utilize a systems biology analysis to define the immune alteration underlying the diminished responses to influenza vaccines in this group of patients. This will form a ground for development of new immuneenhancing strategies. We will focus on systems biology analysis of three cellular compartments that are essential for the generation and the quality of antibody responses to vaccines - the inducers (dendritic cells/monocytes and their subsets);regulators (T follicular helper cells - Tfh), and effectors (B cells). To date, there are no studies describing a systematic and comprehensive analysis of the reconstitution of these three blood compartments in patients who have undergone autologous HCT. Moreover, Tfh immune reconstitution after transplant (allogeneic or autologous) has not been examined for the identification of these cells until very recently. The alteration(s) in either or all of these compartments will have an impact on the quality of flu vaccine responses after HCT. Thus, our study presents an opportunity to analyze, at a systems level, the responses to flu vaccine in patients who have undergone HCT.
Three aims are proposed:
AIM 1 : To establish the cellular and transcriptional signatures of response to flu vaccination in patients who underwent autologous HCT and in age-matched healthy volunteers.
AIM 2 : To establish the kinetics of blood DC subsets, Tfh and B cell compartments reconstitution in patients who underwent autologous HCT.
AIM 3 : To establish the functional competence of blood DC subsets and Tfh cells in patients who underwent autologous HCT.

Public Health Relevance

People who have bone marrow transplants are susceptible to numerous diseases due to their immunocompromised state. Compounding this is the fact that their immune system doesn't induce strong protective innmunity upon vaccination. This project will use a systems biology approach to examine the immune responses in these patients after vaccination with the goal of improving vaccines strategies for these patients.

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
Hogstad, Brandon; Berres, Marie-Luise; Chakraborty, Rikhia et al. (2018) RAF/MEK/extracellular signal-related kinase pathway suppresses dendritic cell migration and traps dendritic cells in Langerhans cell histiocytosis lesions. J Exp Med 215:319-336
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:
Banchereau, Romain; Cepika, Alma-Martina; Banchereau, Jacques et al. (2017) Understanding Human Autoimmunity and Autoinflammation Through Transcriptomics. Annu Rev Immunol 35:337-370
Silvin, Aymeric; Yu, Chun I; Lahaye, Xavier et al. (2017) Constitutive resistance to viral infection in human CD141+ dendritic cells. Sci Immunol 2:
Schotsaert, Michael; García-Sastre, Adolfo (2017) Inactivated influenza virus vaccines: the future of TIV and QIV. Curr Opin Virol 23:102-106
HIPC-CHI Signatures Project Team; HIPC-I Consortium (2017) Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses. Sci Immunol 2:
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
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
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

Showing the most recent 10 out of 60 publications