Vaccines. An Ebola whole-virus vaccine is protective in nonhuman primates

Abstract

Zaire ebolavirus is the causative agent of the current outbreak of hemorrhagic fever disease in West Africa. Previously, we showed that a whole Ebola virus (EBOV) vaccine based on a replication-defective EBOV (EBOVΔVP30) protects immunized mice and guinea pigs against lethal challenge with rodent-adapted EBOV. Here, we demonstrate that EBOVΔVP30 protects nonhuman primates against lethal infection with EBOV. Although EBOVΔVP30 is replication-incompetent, we additionally inactivated the vaccine with hydrogen peroxide; the chemically inactivated vaccine remained antigenic and protective in nonhuman primates. EBOVΔVP30 thus represents a safe, efficacious, whole-EBOV vaccine candidate that differs from other EBOV vaccine platforms in that it presents all viral proteins and the viral RNA to the host immune system, which might contribute to protective immune responses.

Fig. 1. Virus titers in the blood of infected nonhuman primates

Animals were immunized as shown in Table 1. Four weeks after the last immunization, animals were infected with a lethal dose of EBOV. Shown are EBOV titers in the blood of individual nonhuman primates from each group. Virus titers are shown as 50% tissue culture infective dose (TCID₅₀).

Fig. 2. Immune responses in vaccinated nonhuman primates

IgG antibody responses to EBOV GP 2 weeks after the last vaccination (day –14) and on the day of challenge (day 0). Antibody titers were measured with an ELISA specific for EBOV GP. Titers shown are the highest reciprocal dilution that resulted in an optical density (OD) of ≥0.2.

Fig. 3. Effects of H₂O₂-treatment and gamma-irradiation on the antigenicity of EBOV GP

Using a panel of 19mAbs (1 µg/ml) directed against EBOV GP, we performed an ELISA to examine the antigenicity of gamma-irradiated EBOV (blue) and H₂O₂-treated EBOVΔVP30 (red).