Abstract
The filoviruses, Marburg virus (MARV) and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV) that expresses individual filovirus glycoproteins (GPs) in place of the VSV glycoprotein (G). These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28–35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines.
Highlights
The family Filoviridae is comprised of two genera Ebolavirus (EBOV) and Marburgvirus (MARV) [1]
While previous studies of cynomolgus monkeys vaccinated with the recombinant vesicular stomatitis virus (rVSV)-MARV-GP have failed to detect a cellular immune response elicited by vaccination [10], a strong humoral response has been associated with this vaccine [10,24]
To evaluate the magnitude and longevity of anti-MARV GP immunoglobulin G (IgG) in nonhuman primates (NHPs) vaccinated with rVSV-MARV-GP, we sampled the six vaccinated animals seven days before vaccination (Fig. 1B, Day 407) and on multiple days post-vaccination as shown in Figure 1B, arrows
Summary
The family Filoviridae is comprised of two genera Ebolavirus (EBOV) and Marburgvirus (MARV) [1]. These viruses cause severe and often fatal hemorrhagic fever with case fatality rates ranging from 23–90% depending on the strain and/or species. There are at least five different vaccine candidates that have shown the potential to protect nonhuman primates (NHPs) from lethal MARV infection when challenge occurs 28–42 days post-vaccination. These vaccines include DNA vectors, recombinant Adenovirus (rAd) vectors, combined DNA/rAd vectors, virus-like particles (VLPs), alphavirus replicons, and recombinant vesicular stomatitis virus (rVSV) [4,5,6]
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