1. Long-term Sudan Virus Ebola Survivors Maintain Multiple Antiviral Defense Mechanisms.
- Author
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Sobarzo A, Moné Y, Lang S, Gelkop S, Brangel P, Kuehne AI, McKendry RA, Mell JC, Ahmed A, Davis C, Dye JM, Lutwama JJ, Lobel L, Veas F, and Ehrlich GD
- Subjects
- Humans, Uganda epidemiology, Adult, Female, Male, Immunoglobulin G blood, Immunoglobulin G immunology, Immunity, Innate, Leukocytes, Mononuclear immunology, Immunity, Humoral, Middle Aged, Immunity, Cellular, Adaptive Immunity, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Hemorrhagic Fever, Ebola immunology, Hemorrhagic Fever, Ebola virology, Ebolavirus immunology, Survivors, Antibodies, Viral blood, Antibodies, Viral immunology
- Abstract
Background: The critical issues of sustained memory immunity following ebolavirus disease among long-term survivors are still unclear., Methods: Here, we examine virus-specific immune and inflammatory responses following in vitro challengd in 12 Sudan virus (SUDV) long-term survivors from Uganda's 2000-2001 Gulu outbreak, 15 years after recovery. Total RNA from isolated SUDV-stimulated and unstimulated peripheral blood mononuclear cells was extracted and analyzed. Matched serum samples were also collected to determine SUDV IgG levels and functionality., Results: We detected persistent humoral (58%, 7 of 12) and cellular (33%, 4 of 12) immune responses in SUDV long-term survivors and identified critical molecular mechanisms of innate and adaptive immunity. Gene expression in immune pathways, the interferon signaling system, antiviral defense response, and activation and regulation of T- and B-cell responses were observed. SUDV long-term survivors also maintained robust virus-specific IgG antibodies capable of polyfunctional responses, including neutralizing and innate Fc effector functions., Conclusions: Data integration identified significant correlations among humoral and cellular immune responses and pinpointed a specific innate and adaptive gene expression signature associated with long-lasting immunity. This could help identify natural and vaccine correlates of protection against ebolavirus disease., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
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