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Immune memory to Sudan virus: comparison between two separate disease outbreaks.

Sobarzo A, Eskira Y, Herbert AS, Kuehne AI, Stonier SW, Ochayon DE, Fedida-Metula S, Balinandi S, Kislev Y, Tali N, Lewis EC, Lutwama JJ, Dye JM, Yavelsky V, Lobel L - Viruses (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

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Related in: MedlinePlus

Cytokine levels following EBOV GP1–649 stimulation of whole blood from Kibaale (1-year) and Gulu (12-year) ebolavirus survivors and non-infected controls (CT). Cytokine levels were measured in the plasma supernatants of samples following whole blood stimulation. Normalization of cytokine expression levels was performed by reducing the background (unstimulated value) of each individual stimulated (EBOV GP1–649) sample. Non-infected controls of Kibaale and Gulu are presented as average results since there were no significant changes between the two groups (Data not shown). Mean ± SEM, * p < 0.05.
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viruses-07-00037-f004: Cytokine levels following EBOV GP1–649 stimulation of whole blood from Kibaale (1-year) and Gulu (12-year) ebolavirus survivors and non-infected controls (CT). Cytokine levels were measured in the plasma supernatants of samples following whole blood stimulation. Normalization of cytokine expression levels was performed by reducing the background (unstimulated value) of each individual stimulated (EBOV GP1–649) sample. Non-infected controls of Kibaale and Gulu are presented as average results since there were no significant changes between the two groups (Data not shown). Mean ± SEM, * p < 0.05.

Mentions: Significant elevation of IL-2, IL-5, IL-10 and TNFα expression levels was observed in the Kibaale survivor group and non-infected controls. Comparison between SUDV survivor groups and non-infected controls (Figure 4) demonstrated a significantly higher cytokine cross reactive response mainly in samples from the Gulu group of survivors.


Immune memory to Sudan virus: comparison between two separate disease outbreaks.

Sobarzo A, Eskira Y, Herbert AS, Kuehne AI, Stonier SW, Ochayon DE, Fedida-Metula S, Balinandi S, Kislev Y, Tali N, Lewis EC, Lutwama JJ, Dye JM, Yavelsky V, Lobel L - Viruses (2015)

Cytokine levels following EBOV GP1–649 stimulation of whole blood from Kibaale (1-year) and Gulu (12-year) ebolavirus survivors and non-infected controls (CT). Cytokine levels were measured in the plasma supernatants of samples following whole blood stimulation. Normalization of cytokine expression levels was performed by reducing the background (unstimulated value) of each individual stimulated (EBOV GP1–649) sample. Non-infected controls of Kibaale and Gulu are presented as average results since there were no significant changes between the two groups (Data not shown). Mean ± SEM, * p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4306827&req=5

viruses-07-00037-f004: Cytokine levels following EBOV GP1–649 stimulation of whole blood from Kibaale (1-year) and Gulu (12-year) ebolavirus survivors and non-infected controls (CT). Cytokine levels were measured in the plasma supernatants of samples following whole blood stimulation. Normalization of cytokine expression levels was performed by reducing the background (unstimulated value) of each individual stimulated (EBOV GP1–649) sample. Non-infected controls of Kibaale and Gulu are presented as average results since there were no significant changes between the two groups (Data not shown). Mean ± SEM, * p < 0.05.
Mentions: Significant elevation of IL-2, IL-5, IL-10 and TNFα expression levels was observed in the Kibaale survivor group and non-infected controls. Comparison between SUDV survivor groups and non-infected controls (Figure 4) demonstrated a significantly higher cytokine cross reactive response mainly in samples from the Gulu group of survivors.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus