Cell-targeting antibodies in immunity to Ebola

Abstract

As the 2014–15 Ebola virus epidemic in West Africa evolved from emergency to lesson, developers of both vaccines and therapeutic antibodies were left with the puzzlement of what kinds of anti-Ebola antibodies are predictably desirable in treating the afflicted, and what antibodies might account for the specific and lasting protection elicited by the more effective vaccines. The facile answer in virology is that neutralizing antibody (NAb) is desired and required. However, with Ebola and other filoviruses (as with many prior viral examples), there are multiple discordances in which neutralizing antibodies fail to protect animals, and others in which antibody-mediated protection is observed in the absence of measured virus neutralization. Explanation presumably resides in the protective role of antibodies that bind and functionally ‘target’ virus-infected cells, here called ‘cell-targeting antibody’, or CTAb. To be clear, many NAbs are also CTAbs, and in the case of Ebola the great majority of NAbs are likely CTAbs. Isotype, glycosylation, and other features of CTAbs are likely crucial in their capacity to mediate protection. Overall, results and analysis invite an increasingly complex view of antibody-mediated immunity to enveloped viruses.

Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice

“…Our finding is consistent with a previous meta-analysis, demonstrating that Ig levels against the whole EBOV GP correlate strongly with the protection conferred (37). However, this robust correlation with Ig responses was not associated with evidence of serum neutralization of EBOV GP/VSVΔG pseudovirions in our in vitro assays, as others have also reported (12,13,62). In combination with our passive serum transfer studies, our findings provide evidence that our vaccine elicits protective humoral responses that are independent of neutralizing antibodies.…”

Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection

“…More such antibodies could exist for Ebola virus, but may not have been pursued because initial antibody downselection is typically based on neutralization. In many EBOV vaccine studies, total antibody binding, rather than neutralization, is the best correlate of protection (Lennemann et al, 2017; Pushko et al, 2000; Schmaljohn and Lewis, 2016; Sullivan et al, 2009; Wong et al, 2012). Antibodies that recognize the IEF-linked, more accessible Tier 1 epitopes may even take precedence in polyclonal responses elicited by vaccination.…”

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

“…For fluorescence reduction neutralization assay-50% (FRNA 50 ) and plaque reduction neutralizing test-50% (PRNT 50…”

“…Three sequential GMP lots of SAB-139 were produced from the postvaccination plasma of 2 Tc-bovines: lot 1 was produced from the plasma after the third and fourth vaccinations (SAB-139/V3-V4), and Lots 2 and 3 were produced from plasma after the sixth through eighth vaccinations (SAB-139/ V6-V8). The SAB-139 lots were tested for antibody neutralization and/or titers to EBOV GP and/or NP per mg of each lot by PsVNA 50 (Kikwit-95 GP recombinant virus), FRNA 50 (Makona C05 wild-type virus), PRNT 50 (Makona C05 wildtype virus), and an ELISA (Kikwit-95 recombinant GP/NP proteins) as used by the different collaborators ( Table 1). The PsVNA 50 titers for individual vaccination time points (V2, V3-V4, V6-V8) of Tc-bovine nos.…”