The Oropouche virus (OROV) is a member of the Peribunyaviridae family and is an important arthropod-borne virus that causes febrile illnesses, widely distributed in tropical regions of Central and South America. It is transmitted through both urban and sylvatic cycles, primarily by the biting midge Culicoides paraensis. OROV has no known human-to-human transmission and can cause systemic infections, including neurological and blood system complications. Despite its significant public health threat, there are currently no licensed vaccines or specific antiviral treatments for OROV. Recent studies have used immunoinformatics approaches to develop epitope-based peptide vaccines, laying the groundwork for clinical use. OROV has a segmented, single-stranded RNA genome consisting of three segments: Large (L), Medium (M), and Small (S). The L segment encodes the RNA-dependent RNA polymerase (RdRp), the M segment encodes glycoproteins Gn and Gc and a non-structural protein NSm, and the S segment encodes the nucleocapsid protein (N) and a non-structural protein NSs. The virus is enveloped by a helical nucleocapsid and has a spherical lipid envelope. OROV is classified within the Orthobunyavirus genus, with sequences showing close homology to Iquitos and Perdoes viruses. OROV has been detected in numerous countries in South and Central America, with over 500,000 cases reported. It is transmitted through the bite of infected Culicoides paraensis midges and can cause acute febrile illness with symptoms such as fever, headache, muscle pain, and joint pain. In some cases, symptoms may recur one or two weeks after recovery, and there are reports of hemorrhagic symptoms or neurological complications. Currently, there is no specific treatment or vaccine for OROV, and management focuses on symptom relief and supportive care. Recent research has focused on vaccine development, with several strategies being explored, including live attenuated, inactivated, DNA-vectored, and protein-subunit vaccines. A live attenuated vaccine based on the BeAn19991 strain has shown promise in animal models. Additionally, a replication-competent vesicular stomatitis virus (VSV) expressing OROV glycoproteins has demonstrated potential as a vaccine candidate. The development of a reverse genetics system for OROV is expected to significantly benefit vaccine development. OROV is a neglected pathogen with significant public health implications, particularly due to its potential for geographic spread and emergence in new areas. The virus has been detected in non-endemic regions, indicating the possibility of autochthonous circulation. The genetic diversity of OROV and the need for a vaccine that provides broad protection against multiple strains present significant challenges for vaccine development. However, immunoinformatics approaches, VSVThe Oropouche virus (OROV) is a member of the Peribunyaviridae family and is an important arthropod-borne virus that causes febrile illnesses, widely distributed in tropical regions of Central and South America. It is transmitted through both urban and sylvatic cycles, primarily by the biting midge Culicoides paraensis. OROV has no known human-to-human transmission and can cause systemic infections, including neurological and blood system complications. Despite its significant public health threat, there are currently no licensed vaccines or specific antiviral treatments for OROV. Recent studies have used immunoinformatics approaches to develop epitope-based peptide vaccines, laying the groundwork for clinical use. OROV has a segmented, single-stranded RNA genome consisting of three segments: Large (L), Medium (M), and Small (S). The L segment encodes the RNA-dependent RNA polymerase (RdRp), the M segment encodes glycoproteins Gn and Gc and a non-structural protein NSm, and the S segment encodes the nucleocapsid protein (N) and a non-structural protein NSs. The virus is enveloped by a helical nucleocapsid and has a spherical lipid envelope. OROV is classified within the Orthobunyavirus genus, with sequences showing close homology to Iquitos and Perdoes viruses. OROV has been detected in numerous countries in South and Central America, with over 500,000 cases reported. It is transmitted through the bite of infected Culicoides paraensis midges and can cause acute febrile illness with symptoms such as fever, headache, muscle pain, and joint pain. In some cases, symptoms may recur one or two weeks after recovery, and there are reports of hemorrhagic symptoms or neurological complications. Currently, there is no specific treatment or vaccine for OROV, and management focuses on symptom relief and supportive care. Recent research has focused on vaccine development, with several strategies being explored, including live attenuated, inactivated, DNA-vectored, and protein-subunit vaccines. A live attenuated vaccine based on the BeAn19991 strain has shown promise in animal models. Additionally, a replication-competent vesicular stomatitis virus (VSV) expressing OROV glycoproteins has demonstrated potential as a vaccine candidate. The development of a reverse genetics system for OROV is expected to significantly benefit vaccine development. OROV is a neglected pathogen with significant public health implications, particularly due to its potential for geographic spread and emergence in new areas. The virus has been detected in non-endemic regions, indicating the possibility of autochthonous circulation. The genetic diversity of OROV and the need for a vaccine that provides broad protection against multiple strains present significant challenges for vaccine development. However, immunoinformatics approaches, VSV