A Kunjin Replicon Virus-like Particle Vaccine Provides Protection Against Ebola Virus Infection in Nonhuman Primates

Abstract

The current unprecedented outbreak of Ebola virus (EBOV) disease in West Africa has demonstrated the urgent need for a vaccine. Here, we describe the evaluation of an EBOV vaccine candidate based on Kunjin replicon virus-like particles (KUN VLPs) encoding EBOV glycoprotein with a D637L mutation (GP/D637L) in nonhuman primates. Four African green monkeys (Cercopithecus aethiops) were injected subcutaneously with a dose of 10(9) KUN VLPs per animal twice with an interval of 4 weeks, and animals were challenged 3 weeks later intramuscularly with 600 plaque-forming units of Zaire EBOV. Three animals were completely protected against EBOV challenge, while one vaccinated animal and the control animal died from infection. We suggest that KUN VLPs encoding GP/D637L represent a viable EBOV vaccine candidate.

Keywords: Ebola virus; Kunjin replicon; nonhuman primates; vaccine.

Figure 1.

Induction of anti-Ebola virus (EBOV) antibodies (Abs) in immunized animals. A, Titers of anti-EBOV Abs determined by an enzyme-linked immunosorbent assay, using inactivated EBOV as antigen. B, Titers of EBOV-neutralizing Abs determined by a virus-neutralization assay.

Figure 2.

Monitoring of animals after challenge with Ebola virus (EBOV). A, Body temperature measurements of EBOV-infected animals. The dagger indicates time of death. B, Titers of EBOV detected in serum on days 4 and 6 after infection. Abbreviations: PFU, plaque-forming units; SD, standard deviation.