Abstract
Five species of Ebola virus (EBOV) have been identified, with nucleotide differences of 30–45% between species. Four of these species have been shown to cause Ebola hemorrhagic fever (EHF) in humans and a fifth species (Reston ebolavirus) is capable of causing a similar disease in non-human primates. While examining potential serologic cross-reactivity between EBOV species is important for diagnostic assays as well as putative vaccines, the nature of cross-reactive antibodies following EBOV infection has not been thoroughly characterized. In order to examine cross-reactivity of human serologic responses to EBOV, we developed antigen preparations for all five EBOV species, and compared serologic responses by IgM capture and IgG enzyme-linked immunosorbent assay (ELISA) in groups of convalescent diagnostic sera from outbreaks in Kikwit, Democratic Republic of Congo (n = 24), Gulu, Uganda (n = 20), Bundibugyo, Uganda (n = 33), and the Philippines (n = 18), which represent outbreaks due to four different EBOV species. For groups of samples from Kikwit, Gulu, and Bundibugyo, some limited IgM cross-reactivity was noted between heterologous sera-antigen pairs, however, IgM responses were largely stronger against autologous antigen. In some instances IgG responses were higher to autologous antigen than heterologous antigen, however, in contrast to IgM responses, we observed strong cross-reactive IgG antibody responses to heterologous antigens among all sets of samples. Finally, we examined autologous IgM and IgG antibody levels, relative to time following EHF onset, and observed early peaking and declining IgM antibody levels (by 80 days) and early development and persistence of IgG antibodies among all samples, implying a consistent pattern of antibody kinetics, regardless of EBOV species. Our findings demonstrate limited cross-reactivity of IgM antibodies to EBOV, however, the stronger tendency for cross-reactive IgG antibody responses can largely circumvent limitations in the utility of heterologous antigen for diagnostic assays and may assist in the development of antibody-mediated vaccines to EBOV.
Highlights
The genus Ebolavirus, family Filoviridae, has five identified viral species [1]
For all groups of outbreak samples we observed strong cross-reactive IgG antibodies to all Ebola virus (EBOV) species
Our study demonstrates that IgG antibody responses tend to be more crossreactive than IgM antibody responses in people infected with EBOV, a finding that has implications for the development of diagnostic assays and vaccines to EBOV
Summary
The genus Ebolavirus, family Filoviridae, has five identified (including one proposed) viral species [1]. A fifth viral species, Reston ebolavirus (REBOV), has been shown to cause severe disease in non-human primates [10,11,12] and can infect swine [13]. Despite the common characteristic of severe pathogenic potential in humans or non-human primates, genomic sequencing indicates relatively high divergence between Ebola viruses, with nucleotide differences ranging from 30–45% between species [16]. The role of antibody response in viral clearance and protective immunity against Ebola viruses in humans is not fully understood, samples from individuals with acute ZEBOV infection have demonstrated antibodies titers that peak relatively early among those who survive, whereas low or absent antibody titers are commonly present in those with a fatal outcome [17,18]. Others have reported the presence of detectable antiEBOV antibodies in humans during acute EHF (in some instances with concurrent detectable viremia [16,19,20]), as well as in asymptomatic individuals shortly after exposure [21,22], again suggesting that antibody response may be a correlate of protective immunity to EHF
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