Inactivated Rabies Virus–Based Ebola Vaccine Preserved by Vaporization Is Heat-Stable and Immunogenic Against Ebola and Protects Against Rabies Challenge

Abstract

Background Ebola virus (EBOV) is a highly lethal member of the Filoviridae family associated with human hemorrhagic disease. Despite being a sporadic disease, it caused a large outbreak in 2014–2016 in West Africa and another outbreak recently in the Democratic Republic of Congo. Several vaccine candidates are currently in preclinical and clinical studies but none are stable without cold chain storage. Methods We used preservation by vaporization (PBV), a novel processing technology to heat-stabilize FiloRab1 (inactivated rabies-based Ebola vaccine), a candidate Ebola vaccine, and stored the vials at temperatures ranging from 4°C to 50°C for 10 days to 12 months. We immunized Syrian hamsters with the best long-term stable FiloRab1 PBV vaccines and challenged them with rabies virus (RABV). Results Syrian hamsters immunized with FiloRab1 PBV–processed vaccines stored at temperatures of 4°C and 37°C for 6 months, and at 50°C for 2 weeks, seroconverted against both RABV-G and EBOV-GP. Notably, all of the FiloRab1 PBV vaccines proved to be 100% effective in a RABV challenge model. Conclusions We successfully demonstrated that the FiloRab1 PBV vaccines are stable and efficacious for up to 6 months when stored at temperatures ranging from 4°C to 37°C and for up to 2 weeks at 50°C.

Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model

“…This study is the first to show the efficacy of a RABV vectored COVID-19 vaccine, CORAVAX, in the Syrian hamster model of severe disease. The rabies vaccine vector has several advantages: 1) it has an excellent safety profile, as it is used as an inactivated vaccine; 2) there is historical evidence of long-term immunity; 3) it can be administered safely and effectively to the vulnerable populations of children, pregnant women, elderly, and immunocompromised; 4) pre-existing rabies immunity does not affect the boosting potential of the vaccine; 5) RABV virions incorporate foreign antigens easily; and 6) RABV-based vaccines show excellent temperature stability [ 2 , 19 , 28 ].…”

“…Using this approach, we have developed an inactivated viral vector vaccine against SARS-CoV-2 that is based on the rabies virus (RABV). We have previously utilized this approach to develop inactivated RABV-based vaccines for several other human pathogens (e.g., Ebola virus, Marburg virus, Lassa Fever virus and others) [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. These rabies virusbased vaccines have been proven to be highly immunogenic and protective against several emerging viral infections and bacterial toxins, as well as safe and temperature stable [28].…”

Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model

“…This study is the first to show the efficacy of a RABV vectored COVID-19 vaccine, CORAVAX, in the Syrian hamster model of severe disease. The rabies vaccine vector has several advantages: 1) it has an excellent safety profile, as it is used as an inactivated vaccine; 2) there is historical evidence of long-term immunity; 3) it can be administered safely and effectively to the vulnerable populations of children, pregnant women, elderly, and immunocompromised; 4) pre-existing rabies immunity does not affect the boosting potential of the vaccine; 5) RABV virions incorporate foreign antigens easily; and 6) RABV-based vaccines show excellent temperature stability (2,19,28).…”

“…Using this approach, we have developed an inactivated viral vector vaccine against SARS-CoV-2 that is based on the rabies virus (RABV). We have previously utilized this approach to develop inactivated RABV-based vaccines for several other human pathogens (e.g., Ebola virus, Marburg virus, Lassa Fever virus and others) (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). These rabies virus-based vaccines have been proven to be highly immunogenic and protective against several emerging viral infections and bacterial toxins, as well as safe and temperature stable (28).…”

Genetically modified rabies virus vector‐based bovine ephemeral fever virus vaccine induces protective immune responses against BEFV and RABV in mice

“…Currently, there is no commercial rabies vaccine for cattle use in China. Moreover, RABV itself has been proven to be an appealing vector and has been widely used for bivalent vaccine development (Abreu‐Mota et al., 2018; Blaney et al., 2011; Kurup et al., 2019; Shuai et al., 2017; Zhang et al., 2019).…”