Kunjin Virus Replicon-Based Vaccines Expressing Ebola Virus Glycoprotein GP Protect the Guinea Pig Against Lethal Ebola Virus Infection

Abstract

Pre- or postexposure treatments against the filoviral hemorrhagic fevers are currently not available for human use. We evaluated, in a guinea pig model, the immunogenic potential of Kunjin virus (KUN)-derived replicons as a vaccine candidate against Ebola virus (EBOV). Virus like particles (VLPs) containing KUN replicons expressing EBOV wild-type glycoprotein GP, membrane anchor-truncated GP (GP/Ctr), and mutated GP (D637L) with enhanced shedding capacity were generated and assayed for their protective efficacy. Immunization with KUN VLPs expressing full-length wild-type and D637L-mutated GPs but not membrane anchor-truncated GP induced dose-dependent protection against a challenge of a lethal dose of recombinant guinea pig-adapted EBOV. The surviving animals showed complete clearance of the virus. Our results demonstrate the potential for KUN replicon vectors as vaccine candidates against EBOV infection.

A review on the Ebola virus, outbreak history and the current research tools to control the disease

“…Another VLP-producing approach is to use a replicon-recombinant kunjin virus, expressing VLPs with full length Ebolavirus GP or a mutated (D637L) GP. These replicon VLPs induced dose-dependent protection in guinea pigs against a lethal challenge of an adapted Ebolavirus strain [128].…”

Ebola vaccines in clinical trial: The promising candidates

“…42 Reynard et al 43 developed KUN VLPs expressing Ebola virus GP, which were capable of infecting and delivering replicon RNA into most mammalian cell types. Later the vaccines were evaluated in guinea pig model in 2009, vaccinating female, 3-week-old Dunkin-Hartley guinea pigs with 1 £ 10 6 or 5 £ 10 6 vp KUN VLPs expressing fulllength wild-type or D637L-mutated GPs or GP/Ctr intraperitoneally.…”

“…Later the vaccines were evaluated in guinea pig model in 2009, vaccinating female, 3-week-old Dunkin-Hartley guinea pigs with 1 £ 10 6 or 5 £ 10 6 vp KUN VLPs expressing fulllength wild-type or D637L-mutated GPs or GP/Ctr intraperitoneally. 43 Then, 20 d after the prime vaccination, a boosting immunization with the same dosage and type of KUN VLPs was administrated. Only 25%»75% of guinea pigs inoculated with KUN VLPs expressing full-length wild-type or D637L-mutated GPs survived after challenging with a lethal dose of 200 LD 50s of recombinant guinea pig-adapted EBOV.…”

“…However, immunization with KUN VLPs expressing GP/Ctr did not elicit any protection. 43 Pyankov et al 44 injected 4 African green monkeys subcutaneously with 10 9 vp KUN VLPs encoding GP/D637L per animal twice with an interval of 4 weeks, only 75% animals survived from the challenged 3 weeks later with 600 PFU of EBOV (Table 3). Because of the limited efficacy, the KUN VLPs is far away from applying in humans currently, further studies with higher dosages of the vaccine may need to be investigated.…”

Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease

“…While the efficacy of vaccines observed in rodents does not always extend to primates [26], GP-VRP was evaluated in cynomolgus macaques in 2013 and found that a single dose could provide complete protection against intramuscular challenge [58]. membrane anchor-truncated GP and D637L-mutated GP [59]. The surviving animals showed complete clearance of the virus, but the anti-GP-specific antibody response was found to be variable between them.…”