Profile and Persistence of the Virus-Specific Neutralizing Humoral Immune Response in Human Survivors of Sudan Ebolavirus (Gulu)

Sobarzo, Ariel; Groseth, Allison; Dolnik, Olga; Becker, Stephan; Lutwama, Julius J.; Perelman, Eddie; Yavelsky, Victoria; Muhammad, Majidat; Kuehne, Ana I.; Marks, Robert S.; Dye, John M.; Lobel, Leslie

doi:10.1093/infdis/jit162

Cited by 46 publications

(61 citation statements)

References 37 publications

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“…There are no firm correlates of protection for filoviral infections. Approximately half of the sera from SUDV-Gulu outbreak survivors neutralized SUDV-Gulu in plaque reduction neutralization tests (PRNT), as previously reported (49). In contrast, less than 50% of sera from MARV infection survivors neutralized MARV isolates in PRNT (unpublished observations).…”

Section: Discussionsupporting

confidence: 74%

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

Natarajan

Jensen

Keasey

et al. 2016

Clin Vaccine Immunol

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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.

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Section: Discussionsupporting

confidence: 74%

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

Natarajan

Jensen

Keasey

et al. 2016

Clin Vaccine Immunol

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“…Persistent immune responses were also observed in human survivors by means of an ELISA based on full-length recombinant viral proteins of Sudan virus [64], [65]. However, we found that the number of peptides recognized by survivors' sera was significantly lower in sera collected more than ten years after infection than in sera collected during early convalescence.…”

Section: Discussionmentioning

confidence: 54%

Identification of Continuous Human B-Cell Epitopes in the VP35, VP40, Nucleoprotein and Glycoprotein of Ebola Virus

et al. 2014

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Ebola virus (EBOV) is a highly virulent human pathogen. Recovery of infected patients is associated with efficient EBOV-specific immunoglobulin G (IgG) responses, whereas fatal outcome is associated with defective humoral immunity. As B-cell epitopes on EBOV are poorly defined, we sought to identify specific epitopes in four EBOV proteins (Glycoprotein (GP), Nucleoprotein (NP), and matrix Viral Protein (VP)40 and VP35). For the first time, we tested EBOV IgG+ sera from asymptomatic individuals and symptomatic Gabonese survivors, collected during the early humoral response (seven days after the end of symptoms) and the late memory phase (7–12 years post-infection). We also tested sera from EBOV-seropositive patients who had never had clinical signs of hemorrhagic fever or who lived in non-epidemic areas (asymptomatic subjects). We found that serum from asymptomatic individuals was more strongly reactive to VP40 peptides than to GP, NP or VP35. Interestingly, anti-EBOV IgG from asymptomatic patients targeted three immunodominant regions of VP40 reported to play a crucial role in virus assembly and budding. In contrast, serum from most survivors of the three outbreaks, collected a few days after the end of symptoms, reacted mainly with GP peptides. However, in asymptomatic subjects the longest immunodominant domains were identified in GP, and analysis of the GP crystal structure revealed that these domains covered a larger surface area of the chalice bowl formed by three GP1 subunits. The B-cell epitopes we identified in the EBOV VP35, VP40, NP and GP proteins may represent important tools for understanding the humoral response to this virus and for developing new antibody-based therapeutics or detection methods.

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“…In addition, recent evidence from long recovered SUDV survivors has demonstrated several distinctive profiles of immunity, which included persistent and strong IgG neutralizing humoral immunity more than a decade post infection in some survivors 10, 11 . However, other studies have also documented a significant number of convalesced patients with no residual humoral or cell mediated memory immune responses 12 . As such, it is clear that a comprehensive picture of immunity to ebolavirus is lacking, as well as an understanding of the interplay between components of the human immune system.…”

Section: Introductionmentioning

confidence: 99%

Sudan ebolavirus long recovered survivors produce GP-specific Abs that are of the IgG1 subclass and preferentially bind FcγRI

Radinsky

Edri

Brusilovsky

et al. 2017

Sci Rep

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Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs. We developed a cell-based reporter system to quantitate pathogen-specific antibody binding to FcγRIIIA, FcγRIIA, FcγRIIB and FcγRI. With this system, we demonstrate that anti-GP-specific stimulation of the FcγRI reporter by survivors’ sera was substantially high one year after acute infection, with a slight reduction in activity over a decade post infection. We further demonstrate that GP-specific IgG1 is by far the seroprevalent subclass that retained and even enhanced its presence in the sera, over ten years post infection; the prevalence of other GP-specific IgG subclasses was considerably reduced over time. In accordance, GP-specific FcγRI reporter response and GP-specific total IgG1 subclass correlated in the studied group of Ebola survivors. These observations are important for further informing Ebola vaccine and therapeutic development.

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Profile and Persistence of the Virus-Specific Neutralizing Humoral Immune Response in Human Survivors of Sudan Ebolavirus (Gulu)

Cited by 46 publications

References 37 publications

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

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

Identification of Continuous Human B-Cell Epitopes in the VP35, VP40, Nucleoprotein and Glycoprotein of Ebola Virus

Sudan ebolavirus long recovered survivors produce GP-specific Abs that are of the IgG1 subclass and preferentially bind FcγRI

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