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EBOLA VACCINE. VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain - PubMed

  • ️Thu Jan 01 2015

EBOLA VACCINE. VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain

Andrea Marzi et al. Science. 2015.

Abstract

The latest Ebola virus (EBOV) epidemic spread rapidly through Guinea, Sierra Leone, and Liberia, creating a global public health crisis and accelerating the assessment of experimental therapeutics and vaccines in clinical trials. One of those vaccines is based on recombinant vesicular stomatitis virus expressing the EBOV glycoprotein (VSV-EBOV), a live-attenuated vector with marked preclinical efficacy. Here, we provide the preclinical proof that VSV-EBOV completely protects macaques against lethal challenge with the West African EBOV-Makona strain. Complete and partial protection was achieved with a single dose given as late as 7 and 3 days before challenge, respectively. This indicates that VSV-EBOV may protect humans against EBOV infections in West Africa with relatively short time to immunity, promoting its use for immediate public health responses.

Copyright © 2015, American Association for the Advancement of Science.

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Figures

Fig. 1.
Fig. 1.. Clinical parameters of infected NHPs.

(A) Platelet counts of infected NHPs in EDTA blood at every examination day. Concentrations of aspartate aminotransferase (AST) (B), alanine transaminase (ALT) (C), and alkaline phosphatase (ALP) (D) were determined in serum samples collected on examination days (d) after EBOV-Makona challenge. U, units. Two-way analysis of variance (ANOVA) with Tukey multiple comparison post test was used to determine statistical significance at the level of 0.05 (*) and 0.0001 (****) for data presented in (B) to (D). Error bars indicate SD. (E) Viremia (titers) for individual animals on examination days and time of euthanasia. TCID50, median tissure culture infectious dose. (F) Survival curves showing outcome of the different vaccine groups after challenge. Statistical significance was assessed by using the Kaplan-Meier method.

Fig. 2.
Fig. 2.. Humoral immune responses of NHPs.

EBOV-GP–specific IgG titers were determined in the serum of animals at examination days. (A) Summary of EBOV-GP-IgG titers of all groups. The dotted line marks the enzyme-linked immunosorbent assay (ELISA) cut-off based on titers obtained from negative control animals. Neutralizing antibody titers were determined by using the focus reduction assay against three distinct EBOV strains: (B) EBOV-Makona, the challenge strain; (C) EBOV-Kikwit, the source of the vaccine immunogen; and (D) EBOV-Mayinga, the prototype strain of the species. Data are presented as percent foci reduction in relation to a negative control serum. Bar graphs (average of animals per group) represent the neutralizing activity on day 0 (day of challenge); individual animal serum-neutralizing activity is shown for day 42 after challenge.

Fig. 3.
Fig. 3.. Serum cytokine and chemokine levels of NHPs.

Kinetics of IL-1β, IL-6, IL-15, IFN-γ, IL-10, and MCP-1 were analyzed in serum samples of each animal collected on examination days and time of euthanasia. The dotted line in each panel marks the assay detection limit. Terminal values for the control animal euthanized on day 5 were added to the day-6 time point in this group; similarly, the day-9 time point in the control and day-3 vaccination groups represents all values, including terminal samples obtained from NHPs euthanized on days 7 and 8. BL indicates baseline (before vaccination).

Fig. 4.
Fig. 4.. Serum cytokine levels early after challenge.

Serum concentrations for IFN-α, IL-15, and IFN-γ were determined before vaccination (baseline, BL), on day of challenge (gray region, day 0), and early after EBOV-Makona challenge (day 3). Each square represents an individual animal at the indicated time point. The dotted line in each panel marks the assay detection limit. Two-way ANOVA with Tukey multiple comparison post test was used to determine statistical significance at the level of 0.05 (*), 0.01 (**), and 0.0001 (****) for the day-3 vaccination group.

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