Alphavirus-Based Vaccines

Lundstrom, Kenneth

As alphaviruses have been suggested to be responsible for epidemics in various parts of the world, it has also become important to develop vaccines against alphaviruses themselves (Table 4 ). In this context, protection against airborne virus was observed in BALB/c mice vaccinated with an attenuated VEE strain [112] . In another study, improved protection against VEE challenges was achieved by using a live attenuated V3526 VEE vaccine [113] . Similarly, when a chimeric Eastern equine encephalitis (EEE) and Western equine encephalitis (WEE) virus were applied for the vaccination of C57BL/6 mice, complete protection was observed against lethal challenges with a virulent Eastern equine encephalitis (EEE) virus strain [114] . In attempts to design attenuated alphaviruses for vaccine development, the mechanisms of replication and virus-host interaction have been investigated. In this context, mosquito transmission of Chikungunya (CHIK) virus has been prevented by making their replication dependent on internal ribosome entry sites (IRES) [117] . Although replication does not occur in mosquito cells, replication proceeds efficiently in Vero cells. In another approach, the non-structural genes of the attenuated VEE strain TC-83 and the naturally attenuated EEV strain, respectively, were engineered with the structural genes of CHIK [123] . The chimeric vaccine candidates presented a significantly reduced infectivity of the common urban Aedes aegypti and A. albopictus vectors for CHIK, thereby providing a low risk of virus transmission. A new CHIK virus isolated from an acutely infected human patient was used for the engineering of a synthetic DNA vaccine [116] . When this DNA vaccine was electroporated into mice, robust antigen-specific cellular and humoral responses were obtained, which provided protection against further challenges with CHIK. Furthermore, immunization of macaques demonstrated the induction of neutralizing antibodies similar to those elicited in sera from convalescent human patients. In another DNA vector approach, the VEE 26S structural genes were expressed and administered as an aerosol in nonhuman primates [122] . Vaccination resulted in no viremia in two macaques and low viremia in one animal, whereas it was high in all control animals.