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).
>AHL18328.1 nucleocapsid protein N [Rift Valley fever virus]
MDNYQELAIQFAAQAVDRNEIEQWVREFAYQGFDARRVIELLRQYGGADWEKDAKKMIVLALTRGNKPRR
MMMKMSKEGKATVEALINKYKLKEGNPSRDELTLSRVAAALAGWTCQALVVLSEWLPVTGTTMDGLSPAY
PRHMMHPSFAGMVDPSLPEDYLRAILDAHSLYLLQFSRVINPNLRGRTKEEVAATFTQPMNAAVNSNFIS
HEKRRGFLKAFGLVDSNGKPSAAVMAAAQAYKTAA
>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).
>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).
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 × 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).
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).
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)
3. Rift Valley Fever Virus DNA Vaccine encoding N Protein
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).
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 10^5 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).
The live-attenuated MP-12 strain was generated from pathogenic wild-type strain ZH548.(Ikegami et al., 2015)
g. Immunization Route
Intramuscular injection (i.m.)
h. Description
MP-12 is a live attenuated vaccine derived from wild type pathogenic strain ZH548 with a genome encoding 23 mutations. (Ikegami et al., 2015)
6. TSI-GSD 200 RVF Vaccine
a. Manufacturer:
Salk Institute, Government Service Division
b. Type:
Inactivated or "killed" vaccine
c. Status:
Licensed
d. Host Species for Licensed Use:
Human
e. Antigen
RVF virus
f. Immunization Route
subcutaneous injection
g. Description
A formalin-inactivated and lyophilized product originating fromthe supernatant of cell cultures infected with RVF virus. (Pittman et al., 1999)
IV. References
1. Busquets et al., 2014: Busquets N, Lorenzo G, López-Gil E, Rivas R, Solanes D, Galindo-Cardiel I, Xavier Abad F, RodrÃguez 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. Faburay et al., 2014: Faburay B, Lebedev M, McVey DS, Wilson W, Morozov I, Young A, Richt JA. A glycoprotein subunit vaccine elicits a strong Rift Valley fever virus neutralizing antibody response in sheep. Vector borne and zoonotic diseases (Larchmont, N.Y.). 2014; 14(10); 746-756. [PubMed: 25325319].
3. 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].
4. Kalbina et al., 2016: Kalbina I, Lagerqvist N, Moiane B, Ahlm C, Andersson S, Strid Å, Falk KI. Arabidopsis thaliana plants expressing Rift Valley fever virus antigens: Mice exhibit systemic immune responses as the result of oral administration of the transgenic plants. Protein expression and purification. 2016; 127; 61-67. [PubMed: 27402440].
5. 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].
6. 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].
