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. 2018 Nov 22;218(suppl_5):S553-S564.
doi: 10.1093/infdis/jiy316.

Role of Antibodies in Protection Against Ebola Virus in Nonhuman Primates Immunized With Three Vaccine Platforms

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Free PMC article

Role of Antibodies in Protection Against Ebola Virus in Nonhuman Primates Immunized With Three Vaccine Platforms

Kelly L Warfield et al. J Infect Dis. .
Free PMC article

Abstract

Background: Several vaccine platforms have been successfully evaluated for prevention of Ebola virus (EBOV) disease (EVD) in nonhuman primates and humans. Despite remarkable efficacy by multiple vaccines, the immunological correlates of protection against EVD are incompletely understood.

Methods: We systematically evaluated the antibody response to various EBOV proteins in 79 nonhuman primates vaccinated with various EBOV vaccine platforms. We evaluated the serum immunoglobulin (Ig)G titers against EBOV glycoprotein (GP), the ability of the vaccine-induced antibodies to bind GP at acidic pH or to displace ZMapp, and virus neutralization titers. The correlation of these outcomes with survival from EVD was evaluated by appropriate statistical methods.

Results: Irrespective of the vaccine platform, protection from EVD strongly correlated with anti-GP IgG titers. The GP-directed antibody levels required for protection in animals vaccinated with virus-like particles (VLPs) lacking nucleoprotein (NP) was significantly higher than animals immunized with NP-containing VLPs or adenovirus-expressed GP, platforms that induce strong T-cell responses. Furthermore, protective immune responses correlated with anti-GP antibody binding strength at acidic pH, neutralization of GP-expressing pseudovirions, and the ability to displace ZMapp components from GP.

Conclusions: These findings suggest key quantitative and qualitative attributes of antibody response to EVD vaccines as potential correlates of protection.

Figures

Figure 1.
Figure 1.
Antibody response to double and triple virus-like particle (VLP) vaccination. Total immunoglobulin G titers was determined against GP∆TM (A) and GP∆Muc (B) in cynomolgus macaques vaccinated with the indicated doses of Ebola virus VLPs along with QS-21 as adjuvant.
Figure 2.
Figure 2.
Efficacy of double and triple virus-like particles (VLPs) against Ebola virus (EBOV) challenge in cynomolgus macaques. Survival of macaques vaccinated with VLPs after EBOV challenge was monitored for 28 days (A). Antibody titers against were GP∆TM (B) and GP∆Muc (C) as well as percentage of neutralization (D) are shown for individual animals with the day of death or survivorship indicated on the x-axis. Black symbols signify dead animals and colored symbols indicate the survivors. The red line separates the double VLP-vaccinated survivors from lethal cases with a single exception.
Figure 3.
Figure 3.
(A) The immunoglobulin G response to 3 nucleoprotein (NP) constructs from the 3 animals in study IBT_01220 vaccinated with triple virus-like particles (VLPs). (B) Antibody response of all triple VLP-vaccinated animals listed in Table 2, stratified by survivors (S) and dead (D). (C) Binding of the sera was determined at pH 4.5 or 5.5 relative to binding at pH 7.4 by enzyme-linked immunosorbent assay (ELISA) and plotted against each other. Sera are stratified based on survival from challenge. The numbers in quadrants represent percentage of survival for each quadrant. (D) Kaplan–Meier survival curve of the animals in the 3 vaccine groups.

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