Long-term Sudan Virus Ebola Survivors Maintain Multiple Antiviral Defense Mechanisms

• Published in: The Journal of infectious diseases Vol. 230; no. 2; pp. 426 - 437
• Main Authors: Sobarzo, Ariel, Moné, Yves, Lang, Steven, Gelkop, Sigal, Brangel, Polina, Kuehne, Ana I, McKendry, Rachel A, Mell, Joshua Chang, Ahmed, Azad, Davis, Claytus, Dye, John M, Lutwama, Julius Julian, Lobel, Leslie, Veas, Francisco, Ehrlich, Garth D
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 16.08.2024
• Subjects: Adaptive Immunity; Adult; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antiviral drugs; Blood levels; Cell activation; Defense mechanisms; Ebolavirus - immunology; Female; Gene expression; Hemorrhagic Fever, Ebola - immunology; Hemorrhagic Fever, Ebola - virology; Humans; Humoral immunity; Immune response (cell-mediated); Immune response (humoral); Immunity, Cellular; Immunity, Humoral; Immunity, Innate; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunological memory; Leukocytes (mononuclear); Leukocytes, Mononuclear - immunology; Lymphocytes B; Male; Middle Aged; Molecular modelling; Peripheral blood mononuclear cells; Survivor; Survivors; Uganda - epidemiology; Viruses; Uganda; Sudan; Ebola virus; immune memory; immune effector functions; gene expression
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiad555

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. Our study in naturally recovered long-term Sudan virus survivors revealed durable polyfunctional humoral and cellular memory immune responses with distinctive gene expression signatures, which may provide long-lasting protective immunity and help to define the ebolavirus correlate of protection.