Figure 2: Vaccine platforms used for the development of anti-alphavirus vaccines. Chimeric virus vaccine candidates typically harbor a recombinant RNA genome coding for the non-structural proteins of SINV, and the structural proteins for VEEV, EEEV, or WEEV. Rationally designed, recombinant, attenuated vaccines feature a deleted furin cleavage site between E3 and E2 coding sequences. This results in PE2 (E2 precursor protein) being expressed on the virion surface, along with virus attenuation. Viral replicon particles (VRPs) are non-replicating, but infectious particles, engineered to express a protein antigen (ag) of interest upon infection. Genome replication and gene expression are carried out the by the nonstructural proteins (nsP 1-4). Viruses of various types, including adenoviruses (Ad) have been engineered to express a vaccine antigen upon transduction of target cells. DNA vaccines are typically plasmids that express a vaccine antigen upon entry into target cells. Finally, peptides from viral proteins or whole viral proteins can be administered to elicit a protective immune response.