Abstract Ebola virus (EBOV) is the most virulent pathogens that cause hemorrhagic fever with high mortality rates in humans and nonhuman primates. The postexposure antibody therapies to prevent EBOV infection are considered efficient. However, due to the poor thermal stability of mammalian antibody, their application in the tropics has been limited. Here, we developed a thermostable therapeutic antibody against EBOV based on chicken immunoglobulin Y (IgY). The IgY antibodies demonstrated excellent thermal stability, which retained their neutralizing activity at 25°C for one year, in contrast to conventional polyclonal or monoclonal antibodies (MAbs). We immunized laying hens with a variety of EBOV vaccine candidates and confirmed that VSV Δ G/EBOVGP encoding the EBOV glycoprotein could induce high titer neutralizing antibodies against EBOV. The therapeutic efficacy of immune IgY antibodies in vivo was evaluated in the newborn Balb/c mice model. Lethal dose of virus challenged mice were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. The group receiving a high dose of 10 6 NAU/kg (neutralizing antibody units/kilogram) achieved complete protection with no signs of disease, while the low-dose group was only partially protected. In contrast, all mice receiving naïve IgY died within 10 days. In conclusion, the anti-EBOV IgY exhibits excellent thermostability and protective efficacy, and it is very promising to be developed as alternative therapeutic entities. Author Summary Although several Ebola virus therapeutic antibodies have been reported in recent years, however, due to the poor thermal stability of mammalian antibody, their application in tropical endemic areas has been limited. We developed a highly thermostable therapeutic antibody against EBOV based on chicken immunoglobulin Y (IgY). The IgY antibodies demonstrated excellent thermal stability, which retained their neutralizing activity at 25°C for one year. The newborn mice receiving passive transfer of IgY achieved complete protection against a lethal dose of virus challenge indicating that the anti-EBOV IgY provides a promising countermeasure to solve the current clinical application problems of Ebola antibody-based treatments in Africa.

IgY antibodies against Ebola virus possess post-exposure protection and excellent thermostability