Rift Valley fever vaccines: current and future needs Baptiste Dungu 1 , Baratang A Lubisi 2 and Tetsuro Ikegami 3,4,5 Rift Valley fever (RVF) is a zoonotic mosquito-borne bunyaviral disease associated with high abortion rates, neonatal deaths, and fetal malformations in ruminants, and mild to severe disease in humans. Outbreaks of RVF cause huge economic losses and public health impacts in endemic countries in Africa and the Arabian Peninsula. A proper vaccination strategy is important for preventing or minimizing outbreaks. Vaccination against RVF is not practiced in many countries, however, due to absence or irregular occurrences of outbreaks, despite serological evidence of RVF viral activity. Nonetheless, effective vaccination strategies, and functional national and international multi-disciplinary networks, remain crucial for ensuring availability of vaccines and supporting execution of vaccination in high risk areas for efficient response to RVF alerts and outbreaks. Addresses 1 MCI Sante Animale, Mohammedia, Morocco 2 Onderstepoort Veterinary Institute, Onderstepoort, Pretoria, South Africa 3 Department of Pathology, The University of Texas Medical Branch, Galveston, TX, USA 4 Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, TX, USA 5 Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, Galveston, TX, USA Corresponding author: Ikegami, Tetsuro (teikegam@utmb.edu) Current Opinion in Virology 2018, 29:8–15 This review comes from a themed issue on Preventive and thera- peutic vaccines Edited by Marc van Regenmortel and Martin Friede https://doi.org/10.1016/j.coviro.2018.02.001 1879-6257/ã 2018 Published by Elsevier B.V. Introduction Rift Valley fever (RVF), which is caused by the RVF phlebovirus (RVFV; genus Phlebovirus, family Phenuivir- idae), is a mosquito-borne zoonotic disease that is highly pathogenic to both animals and humans [1,2]. The disease is characterized by high rates of abortions and mortalities in newborn sheep, cattle, and goats, as well as a transient febrile illness in humans with occasional complications that can progress to hemorrhagic fever, neurological dis- orders, or blindness in approximately 1–2% of patients [3]. RVFV can be vertically transmitted via floodwater Aedes spp. mosquitoes, whereas other species of mosquitoes (e. g., Culex spp.) serve as amplifying vectors for RVFV by actively feeding on susceptible animals or humans [4  ,5]. Eggs of floodwater Aedes spp. that are infected with RVFV are present during inter-epizootic periods, and infected mosquitoes can hatch upon flooding [6]. RVF outbreaks could thus be associated with heavy rains or irrigation [7,8]. RVFV possesses a tripartite RNA genome, consisting of Large (L), Medium (M), and Small (S) segments [9]. The S-segment is an ambisense sequence, in which the nega- tive- and positive-sense sequences encode N and NSs proteins, respectively. The L-segment encodes the L protein (RNA-dependent RNA polymerase), whereas the M-segment encodes at least two glycoprotein precur- sor proteins, which generate the 78 kDa protein, NSm protein, Gn protein, and Gc protein via cleavage by signal peptidases [10,11]. The Gn and Gc proteins are envelope glycoproteins that form capsomeres arranged on the sur- face of virions [12,13]. Although different RVFV strains have been isolated from ruminants, mosquitoes, humans, and bats in endemic countries, overall genetic diversity is at most 5% and 2% at the nucleotide and deduced amino acid levels, respectively [14–16]. The geographic distribution of RVF endemic areas has expanded since the first recorded outbreaks in Kenya in 1930–1931 (Figure 1a) [17]. Major RVF outbreaks have now been reported in Northern Africa (Egypt), Eastern Africa (Kenya, Tanzania, Somalia, and Sudan), Southern Africa (South Africa, Namibia, Zimbabwe, Zambia, and Mozambique), and Western Africa (Mauritania, Mali, Senegal, and Niger), as well as outside mainland Africa (Madagascar and The Comoros) and on the Arabian Peninsula (Saudi Arabia and Yemen) [1,18,19  ,20–22]. Approximately 18 000 to 200 000 human cases and 598 deaths were reported in Egypt in the 1977–1978 outbreak [23]. During a RVF outbreak in the Arabian Peninsula, 883 human cases and 124 deaths were reported in Saudi Arabia, and 1328 human cases and 166 deaths were reported in Yemen [24]. More recently, 1107 human cases and 351 deaths were reported in Kenya, Tanzania, and Somalia between 2006 and 2007, and 1174 cases and 241 deaths were reported in Sudan in 2008 [25  ]. A number of animal abortions and deaths have also been reported during RVF outbreaks [24]. The occurrence of new outbreaks in RVF-free regions and further geographical expansion of RVF endemicity is possible in the long term, due to the changing world climate and the presence of competent mosquito vectors Available online at www.sciencedirect.com ScienceDirect Current Opinion in Virology 2018, 29:8–15 www.sciencedirect.com