The Current Progress in the Quest for Vaccines Against the Semliki Forest Virus Complex

The Semliki Forest virus (SFV) complex comprises of arboviruses that are transmitted by arthropod vectors and cause acute febrile illness in humans. In the last seven decades, re-emergence of these viruses has resulted in numerous outbreaks globally, affecting regions including Africa, Americas, Asia, Europe and the Caribbean. These viruses are transmitted to humans by the bite of infected mosquitoes. Symptoms of infection include high fever, severe joint pain, skin rash, muscle pain and headache. Fatal cases were reported, and mortality rate increased during the epidemic of these viruses. There is therefore a need to control the spread of these emerging arboviruses. Given that vaccination is one of the most effective ways to protect populations against viral outbreaks, efforts have been made to develop and test potential vaccine candidates. However, there are still no licensed vaccines available against the medically important viruses in the SFV complex. This review first summarizes the current knowledge of the SFV complex disease pathogenesis. Next, seven strategies that have been applied in vaccine development against these viruses are reviewed, indicating the immune response and efficacies of these vaccine candidates in in vivo models of infection. Finally, the more promising candidates that have entered clinical trials are discussed and insights into the future development of vaccines for viruses of the SFV complex are given.