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Rift Valley Fever virus

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
    4. Host Ranges and Animal Models
  2. Vaccine Related Pathogen Genes
    1. RVFVsMgp1 M protein (Protective antigen)
    2. RVFVsSgp2 N protein (Protective antigen)
  3. Vaccine Information
    1. CAdVax-RVFV glycoprotein
    2. Rift Valley Fever Virus DNA Vaccine encoding N Protein
    3. rMVA-GnGc (Rift Valley fever virus)
  4. References
I. General Information
1. NCBI Taxonomy ID:
11588
2. Disease:
Rift valley fever
3. Introduction
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).
4. Host Ranges and Animal Models
RVFV infects domesticated ruminants and humans (Lagerqvist et al., 2009).
1. RVFVsMgp1 M protein
  • Gene Name : RVFVsMgp1 M protein
  • Sequence Strain (Species/Organism) : Rift Valley fever virus
  • VO ID : VO_0011318
  • NCBI Gene ID : 956559
  • NCBI Protein GI : 27881464
  • Locus Tag : RVFVsMgp1
  • Genbank Accession : M25276
  • Protein Accession : NP_777376
  • Taxonomy ID : 11588
  • Gene Starting Position : 20
  • Gene Ending Position : 3613
  • Gene Strand (Orientation) : +
  • Protein Name : M protein
  • Protein pI : 7.46
  • Protein Weight : 122468.33
  • Protein Length : 1197
  • DNA Sequence : Show Sequence
    >gi|27881463:20-3613 Rift Valley fever virus, complete genome
    AATGTATGTTTTATTAACAATTCTAACCTCGGTTCTGGTGTGTGAAGCGATTATTAGAGTGTCTCTAAGC
    TCCACAAGAGAAGAGACCTGCTTTGGTGACTCCACTAACCCAGAGATGATTGAAGGAGCTTGGGATTCAC
    TCAGAGAGGAGGAGATGCCGGAGGAGCTCTCCTGTTCTATATCAGGCATAAGAGAGGTTAAGACCTCAAG
    CCAGGAGTTATACAGGGCATTAAAAGCCATCATTGCTGCTGATGGCTTGAACAACATCACCTGCCATGGT
    AAGGATCCTGAGGACAAGATTTCCCTCATAAAGGGTCCTCCTCACAAAAAGCGGGTGGGGATAGTTCGGT
    GTGAGAGACGAAGAGATGCTAAGCAAATAGGGAGAAAAACCATGGCAGGGATTGCAATGACAGTCCTTCC
    AGCCTTAGCAGTTTTTGCTTTGGCACCTGTTGTTTTTGCTGAAGACCCCCATCTCAGAAACAGACCAGGG
    AAGGGGCACAACTACATTGACGGGATGACTCAGGAGGATGCCACATGCAAACCTGTGACATATGCTGGGG
    CATGTAGCAGTTTTGATGTCTTGCTTGAAAAGGGAAAATTTCCCCTTTTCCAGTCGTATGCTCATCATAG
    AACTCTACTAGAGGCAGTTCACGACACCATCATTGCAAAGGCTGATCCACCTAGCTGTGACCTTCTGAGT
    GCTCATGGGAACCCCTGCATGAAAGAGAAACTCGTGATGAAGACACACTGTCCAAATGACTACCAGTCAG
    CTCATCACCTCAACAATGACGGGAAAATGGCTTCAGTCAAGTGCCCTCCTAAGTATGAGCTCACTGAAGA
    CTGCAACTTTTGTAGGCAGATGACAGGTGCTAGCCTGAAGAAGGGGTCTTATCCTCTCCAAGACTTGTTT
    TGTCAGTCAAGTGAGGATGATGGATCAAAATTAAAAACAAAAATGAAAGGGGTCTGCGAAGTGGGGGTTC
    AAGCACTCAAAAAGTGTGATGGCCAACTCAGCACTGCACATGAGGTTGTGCCCTTTGCAGTGTTTAAGAA
    CTCAAAGAAGGTTTATCTTGATAAGCTTGACCTTAAGACTGAGGAGAATCTGCTACCAGACTCATTTGTC
    TGTTTCGAGCATAAGGGACAGTACAAAGGAACAATGGACTCTGGTCAGACTAAGAGGGAGCTCAAAAGCT
    TTGATATCTCTCAGTGCCCCAAGATTGGAGGACATGGTAGTAAGAAGTGCACTGGGGACGCAGCATTTTG
    CTCTGCTTATGAGTGCACTGCTCAGTACGCCAATGCCTATTGTTCACATGCTAATGGGTCAGGGATTGTG
    CAGATACAAGTATCAGGGGTCTGGAAGAAGCCTTTATGTGTAGGGTATGAGAGAGTGGTTGTGAAGAGAG
    AACTCTCTGCCAAGCCCATCCAGAGAGTTGAGCCTTGCACAACTTGTATAACCAAATGTGAGCCTCATGG
    ATTGGTTGTCCGATCAACAGGGTTCAAGATATCATCAGCAGTTGCTTGTGCTAGCGGAGTTTGCGTCACA
    GGATCGCAGAGTCCTTCCACCGAGATTACACTCAAGTATCCAGGGATATCCCAGTCTTCTGGGGGGGACA
    TAGGGGTTCACATGGCACACGATGATCAGTCAGTTAGCTCCAAAATAGTAGCTCACTGCCCTCCCCAGGA
    CCCGTGCTTAGTGCATGACTGCATAGTGTGTGCTCATGGCCTGATAAATTACCAGTGTCACACTGCTCTC
    AGTGCCTTTGTTGTTGTGTTTGTATTCAGTTCTATTGCAATAATTTGTTTAGCTATTCTTTATAGGGTGC
    TTAAGTGCCTGAAGATTGCCCCAAGGAAAGTTCTGAATCCACTAATGTGGATCACAGCCTTCATCAGATG
    GATATATAAGAAGATGGTTGCCAGAGTGGCAGACAACATTAATCAAGTGAACAGGGAAATAGGATGGATG
    GAAGGAGGTCAGTTGGTTCTAGGGAACCCTGCCCCTATTCCTCGTCATGCCCCAATCCCACGTTATAGCA
    CATACCTGATGTTATTATTGATTGTCTCATATGCATCAGCATGTTCAGAACTGATTCAGGCAAGCTCCAG
    AATCACCACTTGCTCTACAGAGGGTGTTAACACCAAGTGTAGACTGTCTGGCACAGCATTGATCAGAGCA
    GGGTCAGTTGGGGCAGAGGCTTGTTTGATGTTGAAGGGGGTCAAGGAAGATCAAACCAAGTTCTTAAAGT
    TAAAAACTGTCTCAAGTGAGCTATCATGCAGGGAGGGCCAGAGTTATTGGACTGGGTCCTTTAGCCCTAA
    ATGTTTGAGCTCAAGGAGATGCCACCTTGTCGGGGAATGCCATGTGAATAGGTGTCTGTCTTGGAGGGAC
    AATGAAACTTCAGCAGAGTTTTCATTTGTTGGGGAAAGCACGACCATGCGAGAGAATAAGTGTTTTGAGC
    AATGTGGAGGATGGGGGTGTGGGTGTTTCAATGTGAACCCATCTTGCTTATTTGTGCACACGTATCTGCA
    GTCAGTTAGAAAAGAGGCCCTTAGAGTTTTTAACTGTATCGACTGGGTGCATAAACTCACTCTAGAGATC
    ACAGACTTTGATGGCTCTGTTTCAACAATAGACTTGGGAGCATCATCTAGCCGTTTCACAAACTGGGGTT
    CAGTTAGCCTCTCACTGGACGCAGAGGGCATTTCAGGCTCAAATAGCTTTTCTTTCATTGAGAGCCCAGG
    CAAAGGGTATGCAATTGTTGATGAGCCATTCTCAGAAATTCCTCGGCAAGGGTTCTTGGGGGAGATCAGG
    TGCAATTCAGAGTCCTCAGTCCTGAGTGCTCATGAATCATGCCTTAGGGCACCAAACCTTATCTCATACA
    AGCCCATGATAGATCAATTGGAGTGCACAACAAATCTGATTGATCCCTTTGTTGTCTTTGAGAGGGGTTC
    TCTGCCACAGACAAGGAATGACAAAACCTTTGCAGCTTCAAAAGGAAATAGAGGTGTTCAAGCTTTCTCT
    AAGGGCTCTGTACAAGCTGATCTAACTCTGATGTTTGACAATTTTGAGGTGGACTTTGTGGGAGCAGCCG
    TATCTTGTGATGCCGCCTTCTTAAATTTGACAGGTTGCTATTCTTGCAATGCAGGGGCCAGGGTCTGCCT
    GTCTATCACATCCACAGGAACTGGATCTCTCTCTGCCCACAATAAGGATGGGTCTCTGCATATAGTCCTT
    CCATCAGAGAATGGAACAAAAGACCAGTGTCAGATACTACACTTCACTGTGCCTGAAGTAGAGGAGGAGT
    TTATGTACTCTTGTGATGGAGATGAGCGGCCTCTGTTGGTGAAGGGGACCCTGATAGCCATTGATCCATT
    TGATGATAGGCGGGAAGCAGGGGGGGAATCAACAGTTGTGAATCCAAAATCTGGATCTTGGAATTTCTTT
    GACTGGTTTTCTGGACTCATGAGTTGGTTTGGAGGGCCTCTTAAAACTATACTCCTCATTTGCCTGTATG
    TTGCATTATCAATTGGGCTCTTTTTCCTCCTTATATATCTTGGAGGAACAGGCCTCTCTAAAATGTGGCT
    TGCTGCCACTAAGAAGGCCTCATA
  • Protein Sequence : Show Sequence
    >gi|27881464|ref|NP_777376.1| M protein [Rift Valley fever virus]
    MYVLLTILTSVLVCEAIIRVSLSSTREETCFGDSTNPEMIEGAWDSLREEEMPEELSCSISGIREVKTSS
    QELYRALKAIIAADGLNNITCHGKDPEDKISLIKGPPHKKRVGIVRCERRRDAKQIGRKTMAGIAMTVLP
    ALAVFALAPVVFAEDPHLRNRPGKGHNYIDGMTQEDATCKPVTYAGACSSFDVLLEKGKFPLFQSYAHHR
    TLLEAVHDTIIAKADPPSCDLLSAHGNPCMKEKLVMKTHCPNDYQSAHHLNNDGKMASVKCPPKYELTED
    CNFCRQMTGASLKKGSYPLQDLFCQSSEDDGSKLKTKMKGVCEVGVQALKKCDGQLSTAHEVVPFAVFKN
    SKKVYLDKLDLKTEENLLPDSFVCFEHKGQYKGTMDSGQTKRELKSFDISQCPKIGGHGSKKCTGDAAFC
    SAYECTAQYANAYCSHANGSGIVQIQVSGVWKKPLCVGYERVVVKRELSAKPIQRVEPCTTCITKCEPHG
    LVVRSTGFKISSAVACASGVCVTGSQSPSTEITLKYPGISQSSGGDIGVHMAHDDQSVSSKIVAHCPPQD
    PCLVHDCIVCAHGLINYQCHTALSAFVVVFVFSSIAIICLAILYRVLKCLKIAPRKVLNPLMWITAFIRW
    IYKKMVARVADNINQVNREIGWMEGGQLVLGNPAPIPRHAPIPRYSTYLMLLLIVSYASACSELIQASSR
    ITTCSTEGVNTKCRLSGTALIRAGSVGAEACLMLKGVKEDQTKFLKLKTVSSELSCREGQSYWTGSFSPK
    CLSSRRCHLVGECHVNRCLSWRDNETSAEFSFVGESTTMRENKCFEQCGGWGCGCFNVNPSCLFVHTYLQ
    SVRKEALRVFNCIDWVHKLTLEITDFDGSVSTIDLGASSSRFTNWGSVSLSLDAEGISGSNSFSFIESPG
    KGYAIVDEPFSEIPRQGFLGEIRCNSESSVLSAHESCLRAPNLISYKPMIDQLECTTNLIDPFVVFERGS
    LPQTRNDKTFAASKGNRGVQAFSKGSVQADLTLMFDNFEVDFVGAAVSCDAAFLNLTGCYSCNAGARVCL
    SITSTGTGSLSAHNKDGSLHIVLPSENGTKDQCQILHFTVPEVEEEFMYSCDGDERPLLVKGTLIAIDPF
    DDRREAGGESTVVNPKSGSWNFFDWFSGLMSWFGGPLKTILLICLYVALSIGLFFLLIYLGGTGLSKMWL
    AATKKAS
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The glycoprotein (GP) and nucleocapsid (NC) genes of Rift Valley fever virus (RVFV) were expressed in different expression systems and were evaluated for their ability to protect mice from virulent challenge using a prime-boost regime. Mice vaccinated with a lumpy skin disease virus-vectored recombinant vaccine (rLSDV-RVFV) expressing the two RVFV glycoproteins (G1 and G2, expressed by the RVFV M Segment) developed neutralising antibodies and were fully protected when challenged, as were those vaccinated with a crude extract of truncated G2 glycoprotein (tG2) (Wallace et al., 2006).
2. RVFVsSgp2 N protein
  • Gene Name : RVFVsSgp2 N protein
  • Sequence Strain (Species/Organism) : Rift Valley fever virus
  • VO ID : VO_0011319
  • NCBI Gene ID : 956562
  • NCBI Protein GI : 9632367
  • Locus Tag : RVFVsSgp2
  • Genbank Accession : X53771
  • Protein Accession : NP_049344
  • Taxonomy ID : 11588
  • Segment No : segment S
  • Gene Starting Position : 914
  • Gene Ending Position : 1651
  • Gene Strand (Orientation) : -
  • Protein Name : N protein
  • Protein pI : 9.92
  • Protein Weight : 25842.8
  • Protein Length : 245
  • DNA Sequence : Show Sequence
    >gi|9632365:914-1651 Rift Valley fever virus segment S, complete sequence
    CTTAGGCTGCTGTCTTGTAAGCCTGAGCGGCTGCCATGACAGCAGCTGACGGCTTCCCATTGGAATCCAC
    AAGTCCAAAGGCTTTCAAGAATTCTCTCCTCTTCTCATGGCTTATAAAGTTGCTATTCACTGCTGCATTC
    ATTGGCTGCGTGAACGTTGCAGCAACCTCCTCTTTTGTTCTACCTCGGAGGTTTGGGTTGATGACCCGGG
    AGAACTGCAGCAGATACAGAGAGTGAGCATCTAATATTGCCCTTAGATAGTCTCCTGGTAGAGAAGGATC
    CACCATGCCAGCAAAGCTGGGGTGCATCATATGCCTCGGGTATGCAGGGGATAGGCCGTCCATGGTAGTC
    CCAGTGACAGGAAGCCACTCACTCAAGACGACCAAAGCCTGGCATGTCCAGCCAGCCAAGGCGGCAGCAA
    CTCGTGATAGAGTCAACTCATCCCGGGAAGGATTCCCTTCCTTTAGCTTATACTTGTTGATGAGAGCCTC
    CACAGTTGCTTTGCCTTCTTTCGACATTTTCATCATCATCCTCCTGGGCTTGTTGCCACGAGTTAGAGCC
    AGAACAATCATTTTCTTGGCATCCTTCTCCCAGTCAGCCCCACCATACTGCTTTAAGAGTTCGATAACTC
    TACGGGCATCAAACCCTTGATAAGCAAACTCTCGGACCCACTGTTCAATCTCATTGCGGTCCACTGCTTG
    AGCAGCAAACTGGACTCGAAGCTCTTGATAGTTGTCCA
  • Protein Sequence : Show Sequence
    >gi|9632367|ref|NP_049344.1| N protein [Rift Valley fever virus]
    MDNYQELRVQFAAQAVDRNEIEQWVREFAYQGFDARRVIELLKQYGGADWEKDAKKMIVLALTRGNKPRR
    MMMKMSKEGKATVEALINKYKLKEGNPSRDELTLSRVAAALAGWTCQALVVLSEWLPVTGTTMDGLSPAY
    PRHMMHPSFAGMVDPSLPGDYLRAILDAHSLYLLQFSRVINPNLRGRTKEEVAATFTQPMNAAVNSNFIS
    HEKRREFLKAFGLVDSNGKPSAAVMAAAQAYKTAA
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : 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 (Lagerqvist et al., 2009).
  • Related Vaccine(s): Rift Valley Fever Virus DNA Vaccine encoding N Protein
III. Vaccine Information
1. CAdVax-RVFV glycoprotein
a. Vaccine Ontology ID:
VO_0004642
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
RVFV glycoprotein genes were incorporated into a nonreplicating complex adenovirus (CAdVax) vector platform to develop a RVFV vaccine (Holman et al., 2009).
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Vaccination Protocol: The mice were injected intraperitoneally (i.p.) with 1 × 108 PFU (1 × 1010 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).
  • Vaccine Immune Response Type: VO_0000287
  • Challenge Protocol: Vaccinated and control animals were inoculated with 100 PFU of the ZH501 strain of RVFV by i.p. injection (Holman et al., 2009).
  • Efficacy: 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).
2. Rift Valley Fever Virus DNA Vaccine encoding N Protein
a. Vaccine Ontology ID:
VO_0011399
b. Type:
DNA vaccine
c. Status:
Research
d. Gene Engineering of RVFVsSgp2 N protein
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
e. Vector:
pcDNA3.1/V5-His® TOPO (Lagerqvist et al., 2009)
f. Immunization Route
Gene Gun
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Before immunisation the mice were thoroughly shaved on the abdomen and vaccinated with cDNA encoding the antigens using a gene-gun (Helios™, 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).
  • Challenge Protocol: Mice were injected intraperitoneally (i.p.) with RVFV diluted in sterile PBS to a final volume of 100 μl (Lagerqvist et al., 2009).
  • Efficacy: 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).
3. rMVA-GnGc (Rift Valley fever virus)
a. Vaccine Ontology ID:
VO_0004663
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Host Species as Laboratory Animal Model:
lambs
f. Preparation
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).
g. Immunization Route
Intramuscular injection (i.m.)
h. Sheep Response
  • Vaccination Protocol: 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).
  • Vaccine Immune Response Type: VO_0000287
  • Challenge Protocol: Fourteen days post vaccination, all animals were subcutaneously challenged with 105 TCID50 of the virulent RVFV isolate 56/74 and vaccine efficacy assessed using standard endpoints (Busquets et al., 2014).
  • Efficacy: 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).
IV. References
1. Busquets et al., 2014: 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. Efficacy assessment of an MVA vectored Rift Valley Fever vaccine in lambs. Antiviral research. 2014; ; . [PubMed: 24933081].
2. Holman et al., 2009: Holman DH, Penn-Nicholson A, Wang D, Woraratanadharm J, Harr MK, Luo M, Maher EM, Holbrook MR, Dong JY. A complex adenovirus-vectored vaccine against Rift Valley fever virus protects mice against lethal infection in the presence of preexisting vector immunity. Clinical and vaccine immunology : CVI. 2009; 16(11); 1624-1632. [PubMed: 19776190].
3. Lagerqvist et al., 2009: Lagerqvist N, Näslund J, Lundkvist A, Bouloy M, Ahlm C, Bucht G. Characterisation of immune responses and protective efficacy in mice after immunisation with Rift Valley Fever virus cDNA constructs. Virology journal. 2009; 6; 6. [PubMed: 19149901].
4. Wallace et al., 2006: Wallace DB, Ellis CE, Espach A, Smith SJ, Greyling RR, Viljoen GJ. Protective immune responses induced by different recombinant vaccine regimes to Rift Valley fever. Vaccine. 2006; 24(49-50); 7181-7189. [PubMed: 16870311].
5. Wiki: Rift Valley Fever virus: Rift Valley Fever [http://en.wikipedia.org/wiki/Rift_valley_fever_virus]