Effects of adjuvants in a rabies-vectored Ebola virus vaccine on protection from surrogate challenge

Abstract

Ebola virus is the primary contributor to the global threat of filovirus severe hemorrhagic fever, and Ebola virus disease has a case fatality rate of 50–90%. An inactivated, bivalent filovirus/rabies virus vaccine, FILORAB1, consists of recombinant rabies virus virions expressing the Ebola virus glycoprotein. FILORAB1 is immunogenic and protective from Ebola virus challenge in mice and non-human primates, and protection is enhanced when formulated with toll-like receptor 4 agonist Glucopyranosyl lipid adjuvant (GLA) in a squalene oil-in-water emulsion (SE). Through an adjuvant comparison in mice, we demonstrate that GLA-SE improves FILORAB1 efficacy by activating the innate immune system and shaping a Th1-biased adaptive immune response. GLA-SE adjuvanted mice and those adjuvanted with the SE component are better protected from surrogate challenge, while Th2 alum adjuvanted mice are not. Additionally, the immune response to FILORAB1 is long-lasting, as exhibited by highly-maintained serum antibody titers and long-lived cells in the spleen and bone marrow.

Adjuvanting Property of Aqueous Extract of the Indian Mistletoe, Dendrophthoe falcata

“…It is found in various bodily secretions and tissues, including blood, tears, and saliva [21]. Adjuvants can activate the nonspeci c immune cells, such as macrophages and dendritic cells, leading to the production of various immune mediators and cytokines [22,23]. In this study, lysozyme activity increased several folds in the AE adjuvanted sh.…”

The Development of a Rabies Virus-Vectored Vaccine against Borrelia burgdorferi, Targeting BBI39

“…Five C3H/HeN mice per group were immunized with 10 4 foci-forming units (ffu) of live BNSP333-BBI39 or BNSP333-BBI39 RVG . Since BNSP33-BBI39 RVG incorporates BBI39 into the virion, we also tested it as an inactivated vaccine, both with and without the adjuvant PHAD-SE [ 24 ]. Several studies have demonstrated that PHAD-SE induces a Th1-biased immune response [ 24 , 25 ].…”

“…Since BNSP33-BBI39 RVG incorporates BBI39 into the virion, we also tested it as an inactivated vaccine, both with and without the adjuvant PHAD-SE [ 24 ]. Several studies have demonstrated that PHAD-SE induces a Th1-biased immune response [ 24 , 25 ]. This should induce borreliacidal antibodies that can bind, complement, and protect against Borrelia burgdorferi , as shown in other studies [ 34 , 35 , 36 ].…”

“…Since BBI39 protein immunization was previously adjuvanted with Freund’s adjuvant, an adjuvant not sanctioned for human use, we included the adjuvant PHAD-SE. Finally, as an RABV vector control, we used FiloRab1 [ 24 ], a well-studied BNSP333-vectored vaccine incorporating the Ebola virus glycoprotein. Serum was collected on days 0, 14, 28, and 56 post initial immunization and analyzed for the presence of IgG antibodies against BBI39 and RABV-G by ELISA ( Figure 3 b,c).…”

“…BNSP333 has a simple genome with only five proteins, making it easy to manipulate and allowing for the addition of stably expressed foreign antigens [ 23 ]. The RABV vaccine is highly immunogenic; it induces long-term immunity and a type-1-biased immune response, making it an ideal vector for protection against Bb [ 24 , 25 ]. RABV has been used as a vaccine vector against various infectious diseases, including SARS-CoV-2 (CoraVax) [ 19 ], Lassa virus (LassaRab) [ 26 ], Ebola virus (FiloRab1) [ 27 ], and Crimean Congo Hemorrhagic Fever Virus [ 28 ].…”