Neutralizing antibody fails to impact the course of Ebola virus infection in monkeys

Abstract

Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody.

Figure 1. Plasma Viremia in Macaques Challenged with ZEBOV

Shown is the measured viremia, in log₁₀ pfu per ml, for four antibody-treated monkeys (CH46, CH56, CH57, and CH83) and one untreated control animal (EHD) at days 4, 7, 9, and 10 in plasma by plaque assay as described in Materials and Methods. 50 mg/kg of KZ52 IgG1 human antibody [11] was given intravenously to four rhesus macaques 1 d before and again 4 d after challenge with 1,000 pfu (intramusculary) of the 1995 ZEBOV (Kikwit) isolate. Ab, antibody.

Figure 2. A Large Immunoreactive Monocyte Is Observed in a Blood Vessel in the Kidney of Monkey CH57 Postmortem

Similar cells were observed in analysis of monkeys CH83 and CH56. Typically smaller immunoreactive monocytes are seen with ZEBOV infection [15]. Immunohistochemistry was performed as described in Materials and Methods.