IgY antibodies against Ebola virus possess post-exposure protection in a murine pseudovirus challenge model and excellent thermostability.

Yuan Zhang,Rui Gong,Yang Liu,Deyu Tian,Yunlong Li,Wenjun Liu,Limin Yang,Xiaojuan Jia,Xuan Wang,Yanqiu Wei

doi:10.1371/journal.pntd.0008403

Yuan Zhang, Rui Gong + Show 8 more

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https://doi.org/10.1371/journal.pntd.0008403

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Abstract

Ebola virus (EBOV) is one of the most virulent pathogens that causes hemorrhagic fever and displays high mortality rates and low prognosis rates in both humans and nonhuman primates. The post-exposure antibody therapies to prevent EBOV infection are considered effective as of yet. However, owing to the poor thermal stability of mammalian antibodies, their application in the tropics has remained limited. Therefore, a thermostable therapeutic antibody against EBOV was developed modelled on the poultry(chicken) immunoglobulin Y (IgY). The IgY antibodies retaining their neutralising activity at 25°C for one year, displayed excellent thermal stability, opposed to conventional polyclonal antibodies (pAbs) or monoclonal antibodies (mAbs). Laying hens were immunised with a variety of EBOV vaccine candidates and it was confirmed that VSVΔG/EBOVGP encoding the EBOV glycoprotein could induce high titer neutralising antibodies against EBOV. The therapeutic efficacy of immune IgY antibodies in vivo was evaluated in the newborn Balb/c mice who have been challenged with the VSVΔG/EBOVGP model. Mice that have been challenged with a lethal dose of the pseudovirus were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. The group receiving a high dose of 106 NAU/kg (neutralising antibody units/kilogram) showed complete protection with no symptoms of a disease, while the low-dose group was only partially protected. Conversely, all mice receiving naive IgY died within 10 days. In conclusion, the anti-EBOV IgY exhibits excellent thermostability and protective efficacy. Anti-EBOV IgY shows a lot of promise in entering the realm of efficient Ebola virus treatment regimens.

Highlights

Ebola virus (EBOV) belongs to the Filoviridae family and is the known cause of severe hemorrhagic fever in humans and nonhuman primates (NHPs) [1]
To obtain the most potent anti-EBOV antibody, several EBOV immunogens based on multiple different platforms were prepared, including DNA vaccine, recombinant protein or virus-like particle (EBOV-VLP) sub-unit vaccines, and two viral vector vaccines (VSVΔG/EBOVGP, Ad5/ EBOVGP)
To obtain high titer EBOV neutralising antibodies (NAbs), 5-month-old laying hens were vaccinated with five different immunogens, including 103 or 104 TCID50 VSVΔG/EBOVGP, 100 μg Recombinant EBOVGP (rEBOVGP), 100 μg pCAGGS/EBOVGP, 10 μg EBOV-VLP, and 1011 virus particles Ad5/EBOVGP (Fig 2A)

Summary

Introduction

Ebola virus (EBOV) belongs to the Filoviridae family and is the known cause of severe hemorrhagic fever in humans and nonhuman primates (NHPs) [1]. Since the first epidemic in Zaire (presently known as the Democratic Republic of the Congo, DRC) and Sudan in 1976 [2], recurring outbreaks still occur in Africa, with a case-fatality rate averaging 25–90% [3, 4]. The most significant Ebola outbreak to date has happened in West Africa from 2014 to 2016, infecting more than 28,000 people, causing 11,323 fatalities [5, 6]. High mortality and high infectivity make EBOV a Class A pathogen that constitutes a severe threat in the face of public health

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