Rift Valley Fever virus 11588 Rift valley fever RVFV infects domesticated ruminants and humans (Lagerqvist et al., 2009). Rift Valley Fever (RVF) is a viral zoonosis (affects primarily domestic livestock, but can be passed to humans) causing fever. It is spread by the bite of infected mosquitoes, typically the Aedes or Culex genera. The disease is caused by the RVF virus, a member of the genus Phlebovirus (family Bunyaviridae). The disease was first reported among livestock in Kenya around 1915, but the virus was not isolated until 1931. RVF outbreaks occur across sub-Saharan Africa, with outbreaks occurring elsewhere infrequently (but sometimes severely - in Egypt in 1977-78, several million people were infected and thousands died during a violent epidemic. In Kenya in 1998, the virus claimed the lives of over 400 Kenyans. In September 2000 an outbreak was confirmed in Saudi Arabia and Yemen). In humans the virus can cause several different syndromes. Usually sufferers have either no symptoms or only a mild illness with fever, headache, myalgia and liver abnormalities. In a small percentage of cases (< 2%) the illness can progress to hemorrhagic fever syndrome, meningoencephalitis (inflammation of the brain), or affecting the eye. Patients who become ill usually experience fever, generalized weakness, back pain, dizziness, and weight loss at the onset of the illness. Typically, patients recover within 2–7 days after onset. Approximately 1% of human sufferers die of the disease. Amongst livestock the fatality level is significantly higher. In pregnant livestock infected with RVF there is the abortion of virtually 100% of fetuses. An epizootic (animal disease epidemic) of RVF is usually first indicated by a wave of unexplained abortions (Wiki: Rift Valley Fever virus). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 CAdVax-RVFV glycoprotein VO_0004642 Recombinant vector vaccine Research Intramuscular injection (i.m.) RVFV glycoprotein genes were incorporated into a nonreplicating complex adenovirus (CAdVax) vector platform to develop a RVFV vaccine (Holman et al., 2009). Intramuscular injection (i.m.) The mice were injected intraperitoneally (i.p.) with 1 × 10^8 PFU (1 × 10^10 total viral particles) of CAdVax-RVF or control CAdVax-D on week 0. CAdVax-D is a vector with a backbone identical to that of CAdVax-RVF that expresses dengue virus glycoproteins (22). Some mice also received booster vaccinations of the same dose on week 10 (Holman et al., 2009). VO_0000287 Vaccinated mice were protected against lethal RVFV infection. Additionally, protection was elicited in mice despite preexisting immunity to the adenovirus vector (Holman et al., 2009). Vaccinated and control animals were inoculated with 100 PFU of the ZH501 strain of RVFV by i.p. injection (Holman et al., 2009). ChAdOx1 RVF Live, attenuated vaccine Clinical trial ChAdOx1 adenovirus vector [Ref5942:Jenkin et al., 2023] Intramuscularly into deltoid of non dominant arm ChAdOx1 is composed of the ChADOx1 adenovirus vector expresses a codon optimized transgene for the Rift Valley fever viral Gn and Gc glycoproteins (Jenkin et al., 2023) Intramuscularly into deltoid of non dominant arm licensed Rift Valley fever human vaccine Generic Unknown VO_0012166 Inactivated or "killed" vaccine Licensed A generic representation of inactivated vaccine Rift Valley Fever Virus DNA Vaccine encoding N Protein VO_0011399 DNA vaccine Research pcDNA3.1/V5-His® TOPO [Ref1379:Lagerqvist et al., 2009] Gene Gun Gene Gun DNA vaccine construction BALB/c Before immunisation the mice were thoroughly shaved on the abdomen and vaccinated with cDNA encoding the antigens using a gene-gun (Heliosâ„¢, BioRad Laboratories). The cDNA was administrated four times with two to three week intervals. The primary immunisation was performed using four gene-gun cartridges and the following three boosters with two cartridges (Lagerqvist et al., 2009). Even though complete protection was not achieved by genetic immunisation, four out of eight mice vaccinated with cDNA encoding the nucleocapsid protein displayed no clinical signs of infection after challenge. In contrast, all fourteen control animals displayed clinical manifestations of Rift Valley Fever after challenge (Lagerqvist et al., 2009). Mice were injected intraperitoneally (i.p.) with RVFV diluted in sterile PBS to a final volume of 100 μl (Lagerqvist et al., 2009). rMVA-GnGc (Rift Valley fever virus) VO_0004663 Recombinant vector vaccine Research Intramuscular injection (i.m.) A modified vaccinia virus Ankara (MVA) vectored vaccine encoding the Rift Valley Fever virus (RVFV) glycoproteins Gn and Gc in lambs (Busquets et al., 2014). Intramuscular injection (i.m.) Three groups of six to seven lambs were immunized as follows: one group received the vaccine (termed rMVA-GnGc), a second group received an MVA vector (vector control) and a third group received saline solution (non-vaccinated control) (Busquets et al., 2014). VO_0000287 The data suggests that a single dose of the rMVA-GnGc vaccine may be sufficient to reduce RVFV shedding and duration of viremia but does not provide sterile immunity nor protection from disease. Further optimization of this vaccine approach in lambs is warranted (Busquets et al., 2014). Fourteen days post vaccination, all animals were subcutaneously challenged with 10^5 TCID50 of the virulent RVFV isolate 56/74 and vaccine efficacy assessed using standard endpoints (Busquets et al., 2014). RVF MP-12 Live, attenuated vaccine Licensed Mosquito transmitted viral disease [Ref5941:Ikegami et al., 2015] Intramuscular injection (i.m.) MP-12 is a live attenuated vaccine derived from wild type pathogenic strain ZH548 with a genome encoding 23 mutations. (Ikegami et al., 2015) The live-attenuated MP-12 strain was generated from pathogenic wild-type strain ZH548.(Ikegami et al., 2015) Intramuscular injection (i.m.) Viral N antigens TSI-GSD 200 RVF Vaccine Salk Institute, Government Service Division Inactivated or "killed" vaccine Licensed subcutaneous injection A formalin-inactivated and lyophilized product originating fromthe supernatant of cell cultures infected with RVF virus. (Pittman et al., 1999) subcutaneous injection RVF virus RVFVsSgp2 N protein Rift Valley fever virus VO_0011319 956562 9632367 RVFVsSgp2 X53771 NP_049344 11588 segment S 914 1651 - N protein 9.92 25842.8 245 >NC_002045.1:914-1651 Rift Valley fever virus segment S, complete sequence CTTAGGCTGCTGTCTTGTAAGCCTGAGCGGCTGCCATGACAGCAGCTGACGGCTTCCCATTGGAATCCAC AAGTCCAAAGGCTTTCAAGAATTCTCTCCTCTTCTCATGGCTTATAAAGTTGCTATTCACTGCTGCATTC ATTGGCTGCGTGAACGTTGCAGCAACCTCCTCTTTTGTTCTACCTCGGAGGTTTGGGTTGATGACCCGGG AGAACTGCAGCAGATACAGAGAGTGAGCATCTAATATTGCCCTTAGATAGTCTCCTGGTAGAGAAGGATC CACCATGCCAGCAAAGCTGGGGTGCATCATATGCCTCGGGTATGCAGGGGATAGGCCGTCCATGGTAGTC CCAGTGACAGGAAGCCACTCACTCAAGACGACCAAAGCCTGGCATGTCCAGCCAGCCAAGGCGGCAGCAA CTCGTGATAGAGTCAACTCATCCCGGGAAGGATTCCCTTCCTTTAGCTTATACTTGTTGATGAGAGCCTC CACAGTTGCTTTGCCTTCTTTCGACATTTTCATCATCATCCTCCTGGGCTTGTTGCCACGAGTTAGAGCC AGAACAATCATTTTCTTGGCATCCTTCTCCCAGTCAGCCCCACCATACTGCTTTAAGAGTTCGATAACTC TACGGGCATCAAACCCTTGATAAGCAAACTCTCGGACCCACTGTTCAATCTCATTGCGGTCCACTGCTTG AGCAGCAAACTGGACTCGAAGCTCTTGATAGTTGTCCA >NP_049344.1 N protein [Rift Valley fever virus] MDNYQELRVQFAAQAVDRNEIEQWVREFAYQGFDARRVIELLKQYGGADWEKDAKKMIVLALTRGNKPRR MMMKMSKEGKATVEALINKYKLKEGNPSRDELTLSRVAAALAGWTCQALVVLSEWLPVTGTTMDGLSPAY PRHMMHPSFAGMVDPSLPGDYLRAILDAHSLYLLQFSRVINPNLRGRTKEEVAATFTQPMNAAVNSNFIS HEKRREFLKAFGLVDSNGKPSAAVMAAAQAYKTAA Protective antigen Immunisation of mice with cDNA encoding the nucleocapsid protein induced strong humoral and lymphocyte proliferative immune responses. Even though complete protection was not achieved by genetic immunisation, four out of eight mice vaccinated with cDNA encoding the nucleocapsid protein displayed no clinical signs of infection after challenge. In contrast, all fourteen control animals displayed clinical manifestations of Rift Valley Fever after challenge [Ref1379:Lagerqvist et al., 2009]. Busquets et al., 2014 journal Busquets N, Lorenzo G, López-Gil E, Rivas R, Solanes D, Galindo-Cardiel I, Xavier Abad F, Rodríguez F, Bensaid A, Warimwe G, Gilbert SC, Domingo M, Brun A 2014 Antiviral research Faburay et al., 2014 journal Faburay B, Lebedev M, McVey DS, Wilson W, Morozov I, Young A, Richt JA 2014 14 10 746-756 Vector borne and zoonotic diseases (Larchmont, N.Y.) Holman et al., 2009 journal Holman DH, Penn-Nicholson A, Wang D, Woraratanadharm J, Harr MK, Luo M, Maher EM, Holbrook MR, Dong JY 2009 16 11 1624-1632 Clinical and vaccine immunology : CVI Kalbina et al., 2016 journal Kalbina I, Lagerqvist N, Moiane B, Ahlm C, Andersson S, Strid Å, Falk KI 2016 127 61-67 Protein expression and purification Lagerqvist et al., 2009 journal Lagerqvist N, Näslund J, Lundkvist A, Bouloy M, Ahlm C, Bucht G 2009 6 6 Virology journal Wallace et al., 2006 journal Wallace DB, Ellis CE, Espach A, Smith SJ, Greyling RR, Viljoen GJ 2006 24 49-50 7181-7189 Vaccine Wiki: Rift Valley Fever virus website http://en.wikipedia.org/wiki/Rift_valley_fever_virus