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

The critical issues of sustained memory immunity following ebolavirus disease among long-term survivors (EVD) are still unclear.Here, we examine virus-specific immune and inflammatory responses in 12 Sudan virus (SUDV) long-term survivors from Uganda's 2000-1 Gulu outbreak, 15 years after recovery following in vitro challenge. Total RNA from isolated SUDV-stimulated and unstimulated PBMCs was extracted and analyzed. Matched serum samples were also collected to determine SUDV IgG levels and functionality.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 IFN 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.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.