Ebola-Specific CD8 + and CD4 + T-Cell Responses in Sierra Leonean Ebola Virus Survivors With or Without Post-Ebola Sequelae

Background. Ebola virus (EBOV) disease has killed thousands of West and Central Africans over the past several decades. Many who survive the acute disease later experience post-Ebola syndrome, a constellation of symptoms whose causative pathogenesis is unclear. Methods. We investigated EBOV-specific CD8 + and CD4 + T-cell responses in 37 Sierra Leonean EBOV disease survivors with (n = 19) or without (n = 18) sequelae of arthralgia and ocular symptoms. Peripheral blood mononuclear cells were infected with recombinant vesicular stomatitis virus encoding EBOV antigens. We also studied the presence of EBOV-specific immunoglobulin G, antinuclear antibodies, anti–cyclic citrullinated peptide antibodies, rheumatoid factor, complement levels, and cytokine levels in these 2 groups. Results. Survivors with sequelae had a significantly higher EBOV-specific CD8 + and CD4 + T-cell response. No differences in EBOV-specific immunoglobulin G, antinuclear antibody, or anti–cyclic citrullinated peptide antibody levels were found. Survivors with sequelae showed significantly higher rheumatoid factor levels. Conclusion. EBOV-specific CD8 + and CD4 + T-cell responses were significantly higher in Ebola survivors with post-Ebola syndrome. These findings suggest that pathogenesis may occur as an immune-mediated disease via virus-specific T-cell immune response or that persistent antigen exposure leads to increased and sustained T-cell responses.

[1]  Pardis C Sabeti,et al.  Identification of Common CD8+ T Cell Epitopes from Lassa Fever Survivors in Nigeria and Sierra Leone , 2020, Journal of Virology.

[2]  Pardis C Sabeti,et al.  High crossreactivity of human T cell responses between Lassa virus lineages , 2020, PLoS pathogens.

[3]  J. Sidney,et al.  Longitudinal Analysis of the Human B Cell Response to Ebola Virus Infection , 2019, Cell.

[4]  J. Neaton,et al.  A Longitudinal Study of Ebola Sequelae in Liberia , 2019, The New England journal of medicine.

[5]  Karthik Gangavarapu,et al.  Analysis of CD8+ T cell response during the 2013–2016 Ebola epidemic in West Africa , 2018, Proceedings of the National Academy of Sciences.

[6]  E. Kenu,et al.  Post-Ebola Syndrome among Ebola Virus Disease Survivors in Montserrado County, Liberia 2016 , 2018, BioMed research international.

[7]  Dianna D. Carroll,et al.  Trust, fear, stigma and disruptions: community perceptions and experiences during periods of low but ongoing transmission of Ebola virus disease in Sierra Leone, 2015 , 2018, BMJ Global Health.

[8]  A. Adebajo,et al.  Musculoskeletal manifestations of Ebola virus , 2018, Rheumatology.

[9]  Livia Navon Using Emergency Medical Services (EMS) Data to Assess Personal Protective Equipment (PPE) Reporting By Illinois EMS Providers in Response to the 2014–2016 Ebola Outbreak in West Africa , 2017 .

[10]  Mohamed A. Vandi,et al.  Sequelae and Other Conditions in Ebola Virus Disease Survivors, Sierra Leone, 2015 , 2017, Emerging infectious diseases.

[11]  Jay B. Varkey,et al.  Ebola Virus Persistence in Semen of Male Survivors. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[12]  R. Fowler,et al.  Early clinical sequelae of Ebola virus disease in Sierra Leone: a cross-sectional study. , 2016, The Lancet. Infectious diseases.

[13]  A. Chughtai,et al.  Recurrence and reinfection--a new paradigm for the management of Ebola virus disease. , 2016, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[14]  Jay B. Varkey,et al.  Human Ebola virus infection results in substantial immune activation , 2015, Proceedings of the National Academy of Sciences.

[15]  F. Ennis,et al.  Cross-reactive human B cell and T cell epitopes between influenza A and B viruses , 2013, Virology Journal.

[16]  M. Whitt Generation of VSV pseudotypes using recombinant ΔG-VSV for studies on virus entry, identification of entry inhibitors, and immune responses to vaccines. , 2010, Journal of Virological Methods.

[17]  Bjoern Peters,et al.  Ab and T cell epitopes of influenza A virus, knowledge and opportunities , 2007, Proceedings of the National Academy of Sciences.

[18]  Claudio Michelassi,et al.  Mixed cryoglobulinemia: demographic, clinical, and serologic features and survival in 231 patients. , 2004, Seminars in arthritis and rheumatism.

[19]  A. Sanchez,et al.  The reemergence of Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidémies à Kikwit. , 1999, The Journal of infectious diseases.

[20]  J Bertolli,et al.  Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit. , 1999, The Journal of infectious diseases.

[21]  R. Colebunders,et al.  Late ophthalmologic manifestations in survivors of the 1995 Ebola virus epidemic in Kikwit, Democratic Republic of the Congo. , 1999, The Journal of infectious diseases.

[22]  P. Simmonds,et al.  Extrahepatic Immunologic Manifestations in Chronic Hepatitis C and Hepatitis C Virus Serotypes , 1995, Annals of Internal Medicine.

[23]  M. Tsang,et al.  Aggregation of the chemokine MIP-1 alpha is a dynamic and reversible phenomenon. Biochemical and biological analyses. , 1994, The Journal of biological chemistry.

[24]  T. Delbanco,et al.  The rheumatoid factor: an analysis of clinical utility. , 1991, The American journal of medicine.

[25]  S. Podos Ocular Differential Diagnosis , 1972 .

[26]  M. Oldstone VIRUS INDUCED AUTOIMMUNE DISEASE: VIRUSES IN THE PRODUCTION AND PREVENTION OF AUTOIMMUNE DISEASE , 1972 .