Post-exposure treatment of non-human primates lethally infected with Ebola virus with EBOTAb, a purified ovine IgG product

Abstract

Despite sporadic outbreaks of Ebola virus (EBOV) over the last 4 decades and the recent public health emergency in West Africa, there are still no approved vaccines or therapeutics for the treatment of acute EBOV disease (EVD). In response to the 2014 outbreak, an ovine immunoglobulin therapy was developed, termed EBOTAb. After promising results in the guinea pig model of EBOV infection, EBOTAb was tested in the cynomolgus macaque non-human primate model of lethal EBOV infection. To ensure stringent therapeutic testing conditions to replicate likely clinical usage, EBOTAb was first delivered 1, 2 or 3 days post-challenge with a lethal dose of EBOV. Results showed a protective effect of EBOTAb given post-exposurally, with survival rates decreasing with increasing time after challenge. Viremia results demonstrated that EBOTAb resulted in a decreased circulation of EBOV in the bloodstream. Additionally, assay of liver enzymes and histology analysis of local tissues identified differences between EBOTAb-treated and untreated groups. The results presented demonstrate that EBOTAb conferred protection against EBOV when given post-exposure and should be explored and developed further as a potential intervention strategy for future outbreaks, which are likely to occur.

Adjuvant formulated virus-like particles expressing native-like forms of the Lassa virus envelope surface glycoprotein are immunogenic and induce antibodies with broadly neutralizing activity

“…Passive antibody therapy has long been used in the treatment and postexposure prophylaxis of various diseases, including viral infections and the development of heterologous polyclonal antibody preparations obtained from hyperimmunized animals against several highly pathogenic viruses such as Ebola, Junín, and Nipah 40,46,61,62 . Our VLP-based approach combines several advantages for therapeutic antibody production.…”

Virus specific antibody - based remedies for the urgent prevention and treatment of Ebola virus disease

“…Dye и соавт. установлено, что гибель обезьян при перфузии крови иммунных животных обусловлена неудачной схемой введения (немедленно после инфицирования) [13]. Макакам резус, внутримышечно инфицированным вирусом Эбола-Заир, штамм Киквит, в дозе 1×10 3 БОЕ вводили по 200…250 мл плазмы реконвалесцентов от разных доноров.…”

“…Среди препаратов данного класса необходимо отметить разработанный во время вспышки ЗВВЭ в Западной Африке в 2014-2016 гг. гетерологичный овечий иммуноглобулин (EBOTAb), который показал вируснейтрализующую активность и защитную эффективность при лечении инфицированных морских свинок [11,13].…”

“…Выявлены различия по уровню вирусемии между группами с лечением и без лечения. Различия составили примерно 3-4 порядка [1×10 5 в леченной группе, 1×10 8 , 1×10 9 РНК-копий в 1 мл -в контроле (без лечения)] [13].…”

Prophylactic Efficacy of Equine Immunoglobulin F(ab′)2 Fragments Against Feline Parvovirus

“…F(ab′) 2 fragments, being bivalent, are easier to purify in large quantities and more able to penetrate deeper into the tissue than the IgG antibody [6], thus increasing the time for excretion from the blood. There are reports on using F(ab′) 2 fragments to prevent West Nile virus (WNV) [7], feline calicivirus [8], Middle East respiratory syndrome coronavirus (MERS-CoV) [9] and Ebola virus (EBOV) [10,11].…”