Abstract

Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against Ebola glycoprotein in mice and guinea pigs. Immunocompetent mice or guinea pigs were given MAbs i.p. in various doses individually or as pools of 3–4 MAbs to test their protection against a lethal challenge with mouse- or guinea pig-adapted EBOV. Each of the 8 MAbs (100 µg) protected mice from a lethal EBOV challenge when administered 1 day before or after challenge. Seven MAbs were effective 2 days post-infection (dpi), with 1 MAb demonstrating partial protection 3 dpi. In the guinea pigs each MAb showed partial protection at 1 dpi, however the mean time to death was significantly prolonged compared to the control group. Moreover, treatment with pools of 3–4 MAbs completely protected the majority of animals, while administration at 2–3 dpi achieved 50–100% protection. This data suggests that the MAbs generated are capable of protecting both animal species against lethal Ebola virus challenge. These results indicate that MAbs particularly when used as an oligoclonal set are a potential therapeutic for post-exposure treatment of EBOV infection.

Highlights

  • Ebola virus (EBOV) is a filovirus causing severe viral haemorrhagic fever in humans and non-human primates (NHPs) [1]

  • This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against the Ebola virus surface glycoprotein, in mice and guinea pigs

  • There was 100% survival when guinea pigs received a mix of 3 neutralizing MAbs two days after a challenge with 1,000 LD50 of guinea pigadapted EBOV

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Summary

Introduction

Ebola virus (EBOV) is a filovirus causing severe viral haemorrhagic fever in humans and non-human primates (NHPs) [1]. Several studies have been conducted to determine the immune correlates of protection in EBOV infections either by following natural infections, or in in vivo animal models [9,10,11,12,13,14,15]. Both T and B cell immunity was analysed and it was believed that a strong early humoral immune response may have been a factor in survival [11,16,17]. In mice experiments EBOV-specific sera was sufficient for improving survival [10,18,19]

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