title: Human Ebola virus infection results in substantial immune activation.
abstract: Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.
authors.affiliation: Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333; Division of Pediatric Infectious Disease.
authors.forename: Anita K
authors.initials: AK
authors.lastname: McElroy
authors.affiliation: Emory Vaccine Center, Department of Microbiology and Immunology.
authors.forename: Rama S
authors.initials: RS
authors.lastname: Akondy
authors.affiliation: Emory Vaccine Center, Department of Microbiology and Immunology.
authors.forename: Carl W
authors.initials: CW
authors.lastname: Davis
authors.affiliation: Emory Vaccine Center, Department of Microbiology and Immunology.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Ellebedy
authors.affiliation: Division of Infectious Diseases, and.
authors.forename: Aneesh K
authors.initials: AK
authors.lastname: Mehta
authors.affiliation: Division of Infectious Diseases, and Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322; and.
authors.forename: Colleen S
authors.initials: CS
authors.lastname: Kraft
authors.affiliation: Division of Infectious Diseases, and.
authors.forename: G Marshall
authors.initials: GM
authors.lastname: Lyon
authors.affiliation: Division of Infectious Diseases, and.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Ribner
authors.affiliation: Division of Infectious Diseases, and.
authors.forename: Jay
authors.initials: J
authors.lastname: Varkey
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.affiliation: Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333;
authors.forename: Shelley
authors.initials: S
authors.lastname: Campbell
authors.affiliation: Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333;
authors.forename: Ute
authors.initials: U
authors.lastname: Ströher
authors.affiliation: Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333;
authors.forename: Inger
authors.initials: I
authors.lastname: Damon
authors.affiliation: Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333;
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Nichol
authors.affiliation: Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333; ccs8@cdc.gov rahmed@emory.edu.
authors.forename: Christina F
authors.initials: CF
authors.lastname: Spiropoulou
authors.affiliation: Emory Vaccine Center, Department of Microbiology and Immunology, ccs8@cdc.gov rahmed@emory.edu.
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D029043:Ebolavirus / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D019142:Hemorrhagic Fever, Ebola / Q000097:blood / Q000276:immunology* / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D007371:Interferon-gamma
keywords: Ebola infection; T cells; human immune response; immune activation; plasmablasts