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Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses.

ABSTRACT: A detailed understanding of serological immune responses to Ebola and Marburg virus infections will facilitate the development of effective diagnostic methods, therapeutics, and vaccines. We examined antibodies from Ebola or Marburg survivors 1 to 14 years after recovery from disease, by using a microarray that displayed recombinant nucleoprotein (NP), viral protein 40 (VP40), envelope glycoprotein (GP), and inactivated whole virions from six species of filoviruses. All three outbreak cohorts exhibited significant antibody responses to antigens from the original infecting species and a pattern of additional filoviruses that varied by outbreak. NP was the most cross-reactive antigen, while GP was the most specific. Antibodies from survivors of infections by Marburg marburgvirus (MARV) species were least cross-reactive, while those from survivors of infections by Sudan virus (SUDV) species exhibited the highest cross-reactivity. Based on results revealed by the protein microarray, persistent levels of antibodies to GP, NP, and VP40 were maintained for up to 14 years after infection, and survival of infection caused by one species imparted cross-reactive antibody responses to other filoviruses.

SUBMITTER: Natesan M

PROVIDER: S-EPMC4979172 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses.

Natesan Mohan M Jensen Stig M SM Keasey Sarah L SL Kamata Teddy T Kuehne Ana I AI Stonier Spencer W SW Lutwama Julius Julian JJ Lobel Leslie L Dye John M JM Ulrich Robert G RG

Clinical and vaccine immunology : CVI 20160805 8

A detailed understanding of serological immune responses to Ebola and Marburg virus infections will facilitate the development of effective diagnostic methods, therapeutics, and vaccines. We examined antibodies from Ebola or Marburg survivors 1 to 14 years after recovery from disease, by using a microarray that displayed recombinant nucleoprotein (NP), viral protein 40 (VP40), envelope glycoprotein (GP), and inactivated whole virions from six species of filoviruses. All three outbreak cohorts ex ...[more]

PMID: 27335383

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Project description:Uganda has reported eight outbreaks caused by filoviruses between 2000 to 2016, more than any other country in the world. We used species distribution modeling to predict where filovirus outbreaks are likely to occur in Uganda to help in epidemic preparedness and surveillance. The MaxEnt software, a machine learning modeling approach that uses presence-only data was used to establish filovirus - environmental relationships. Presence-only data for filovirus outbreaks were collected from the field and online sources. Environmental covariates from Africlim that have been downscaled to a nominal resolution of 1km x 1km were used. The final model gave the relative probability of the presence of filoviruses in the study area obtained from an average of 100 bootstrap runs. Model evaluation was carried out using Receiver Operating Characteristic (ROC) plots. Maps were created using ArcGIS 10.3 mapping software. We showed that bats as potential reservoirs of filoviruses are distributed all over Uganda. Potential outbreak areas for Ebola and Marburg virus disease were predicted in West, Southwest and Central parts of Uganda, which corresponds to bat distribution and previous filovirus outbreaks areas. Additionally, the models predicted the Eastern Uganda region and other areas that have not reported outbreaks before to be potential outbreak hotspots. Rainfall variables were the most important in influencing model prediction compared to temperature variables. Despite the limitations in the prediction model due to lack of adequate sample records for outbreaks, especially for the Marburg cases, the models provided risk maps to the Uganda surveillance system on filovirus outbreaks. The risk maps will aid in identifying areas to focus the filovirus surveillance for early detection and responses hence curtailing a pandemic. The results from this study also confirm previous findings that suggest that filoviruses are mainly limited by the amount of rainfall received in an area.

Project description:BACKGROUND:The 2013-15 Ebola outbreak was unprecedented due to sustained transmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. METHODS:Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. RESULTS:6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. CONCLUSIONS:Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood.

Project description:BackgroundThe 2013-16 Ebola virus disease epidemic in west Africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. The large number of cases provided an opportunity to study the long-term kinetics of Zaire ebolavirus-specific immune response of survivors in addition to known contacts of those infected with the virus.MethodsIn this observational cohort study, we worked with leaders of Ebola virus disease survivor associations in two regions of Guinea, Guéckédou and Coyah, to recruit survivors of Ebola virus disease, contacts from households of individuals known to have had Ebola virus disease, and individuals who were not knowingly associated with infected individuals or had not had Ebola virus disease symptoms to serve as negative controls. We did Zaire ebolavirus glycoprotein-specific T cell analysis on peripheral blood mononuclear cells (PBMCs) on location in Guinea and transported plasma and PBMCs back to Europe for antibody quantification by ELISA, functional neutralising antibody analysis using live Zaire ebolavirus, and T cell phenotype studies. We report on the longitudinal cellular and humoral response among Ebola virus disease survivors and highlight potentially paucisymptomatic infection.FindingsWe recruited 117 survivors of Ebola virus disease, 66 contacts, and 23 negative controls. The mean neutralising antibody titre among the Ebola virus disease survivors 3-14 months after infection was 1/174 (95% CI 1/136-1/223). Individual results varied greatly from 1/10 to more than 1/1000 but were on average ten times greater than that induced after 1 month by single dose Ebola virus vaccines. Following reactivation with glycoprotein peptide, the mean T cell responses among 116 Ebola virus disease survivors as measured by ELISpot was 305 spot-forming units (95% CI 257-353). The dominant CD8+ polyfunctional T cell phenotype, as measured among 53 Ebola virus disease survivors, was interferon γ+, tumour necrosis factor+, interleukin-2-, and the mean response was 0·046% of total CD8+ T cells (95% CI 0·021-0·071). Additionally, both neutralising antibody and T cell responses were detected in six (9%) of 66 Ebola virus disease contacts. We also noted that four (3%) of 117 individuals with Ebola virus disease infections did not have circulating Ebola virus-specific antibodies 3 months after infection.InterpretationThe continuous high titre of neutralising antibodies and increased T cell response might support the concept of long-term protective immunity in survivors. The existence of antibody and T cell responses in contacts of individuals with Ebola virus disease adds further evidence to the existence of sub-clinical Ebola virus infection.FundingUS Food & Drug Administration, Horizon 2020 EU EVIDENT, Wellcome, UK Department for International Development.TranslationFor the French translation of the abstract see Supplementary Materials section.

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Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses.

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Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses.

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