title: Immune memory to Sudan virus: comparison between two separate disease outbreaks.
abstract: Recovery from ebolavirus infection in humans is associated with the development of both cell-mediated and humoral immune responses. According to recent studies, individuals that did not survive infection with ebolaviruses appear to have lacked a robust adaptive immune response and the expression of several early innate response markers. However, a comprehensive protective immune profile has yet to be described. Here, we examine cellular memory immune responses among survivors of two separate Ebolavirus outbreaks (EVDs) due to Sudan virus (SUDV) infection in Uganda-Gulu 2000-2001 and Kibaale 2012. Freshly collected blood samples were stimulated with inactivated SUDV, as well as with recombinant SUDV or Ebola virus (EBOV) GP (GP1-649). In addition, ELISA and plaque reduction neutralization assays were performed to determine anti-SUDV IgG titers and neutralization capacity. Cytokine expression was measured in whole blood cultures in response to SUDV and SUDV GP stimulation in both survivor pools, demonstrating recall responses that indicate immune memory. Cytokine responses between groups were similar but had distinct differences. Neutralizing, SUDV-specific IgG activity against irradiated SUDV and SUDV recombinant proteins were detected in both survivor cohorts. Furthermore, humoral and cell-mediated crossreactivity to EBOV and EBOV recombinant GP1-649 was observed in both cohorts. In conclusion, immune responses in both groups of survivors demonstrate persistent recognition of relevant antigens, albeit larger cohorts are required in order to reach greater statistical significance. The differing cytokine responses between Gulu and Kibaale outbreak survivors suggests that each outbreak may not yield identical memory responses and promotes the merits of studying the immune responses among outbreaks of the same virus. Finally, our demonstration of cross-reactive immune recognition suggests that there is potential for developing cross-protective vaccines for ebolaviruses.
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel. tautau.ariel@gmail.com.
authors.forename: Ariel
authors.initials: A
authors.lastname: Sobarzo
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel. askiray@gmail.com.
authors.forename: Yael
authors.initials: Y
authors.lastname: Eskira
authors.affiliation: Virology Division-U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, Frederick, MD 21701, USA. anderw.s.herbert.ctr@mail.mil.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Herbert
authors.affiliation: Virology Division-U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, Frederick, MD 21701, USA. ana.kuehne@us.army.mil.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Kuehne
authors.affiliation: Virology Division-U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, Frederick, MD 21701, USA. spencer.w.stonier2.ctr@mail.mil.
authors.forename: Spencer W
authors.initials: SW
authors.lastname: Stonier
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel. davidochayon@gmail.com.
authors.forename: David E
authors.initials: DE
authors.lastname: Ochayon
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel. fedida.metula@gmail.com.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Fedida-Metula
authors.affiliation: Department of Arbovirology, Emerging and Re-emerging Infection Uganda Virus Research Institute, Entebbe P.O Box 49, Uganda. hnp6@ug.cdc.ug.
authors.forename: Steven
authors.initials: S
authors.lastname: Balinandi
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel. k.yaarula@gmail.com.
authors.forename: Yaara
authors.initials: Y
authors.lastname: Kislev
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel. netatali20@gmail.com.
authors.forename: Neta
authors.initials: N
authors.lastname: Tali
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel. lewis@bgu.ac.il.
authors.forename: Eli C
authors.initials: EC
authors.lastname: Lewis
authors.affiliation: Department of Arbovirology, Emerging and Re-emerging Infection Uganda Virus Research Institute, Entebbe P.O Box 49, Uganda. jjlutwama03@yahoo.com.
authors.forename: Julius Julian
authors.initials: JJ
authors.lastname: Lutwama
authors.affiliation: Virology Division-U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, Frederick, MD 21701, USA. john.m.dye1.civ@mail.mil.
authors.forename: John M
authors.initials: JM
authors.lastname: Dye
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel. yavelsky@bgu.ac.il.
authors.forename: Victoria
authors.initials: V
authors.lastname: Yavelsky
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel. leslie.lobel@gmail.com.
authors.forename: Leslie
authors.initials: L
authors.lastname: Lobel
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D015331:Cohort Studies; D003429:Cross Reactions; D016207:Cytokines / Q000378:metabolism; D004196:Disease Outbreaks; D029043:Ebolavirus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D019142:Hemorrhagic Fever, Ebola / Q000453:epidemiology* / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D009500:Neutralization Tests; D013397:Sudan; D017741:Survivors; D014454:Uganda / Q000453:epidemiology
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G