Alphavirus-Based Vaccines

Lundstrom, Kenneth

Due to their immunogenic properties, viral structural proteins have been popular targets for alphavirus-based vaccine development [13] (Table 1) . In this context, immunization with SFV particles expressing influenza nucleoprotein (NP) elicited a strong immune response in mice [15] . Moreover, VEE-based expression of influenza hemagglutinin (HA) provided protection against challenges with H5N1 virus in chicken [16] . Similarly, SFV particles expressing the HIV envelope [17] and gp41 [18] Attempts to further improve the immunogenicity of vaccine candidates, the herpes simplex virus type I (HSV-1) VP22 protein was fused to the H5N1 subtype influenza HA [60] . The responses of both interleukin-4 (IL-4) of CD4 + T-cells and interferon-gamma (IFNÉ£) of CD8 + T-cells were observed in vaccinated mice. VEE replicon particles expressing the severe acute respiratory syndrome coronavirus (SARS-CoV) glycoprotein managed to provide protection against challenges with lethal doses of SARS-CoV in vaccinated mice [55] . Furthermore, VEE particles were applied for the expression of glycoproteins from the zoonotic pathogenic Hendra virus (HeV) and Nipah virus (NiV), known to cause fatal infections in both animals and humans [33] . Immunization resulted in enhanced induction of cross-reactive neutralizing antibodies. In another study, mice were vaccinated with both DNA plasmids and alphavirus replicons expressing Rift Valley fever virus (RVFV) glycoprotein Gn fused to the C3d complement protein [54] . The immunization generated neutralizing antibodies and provided protection against challenges with RVFV, which suggested that plasmid DNA and alphavirus replicon approaches, as well as the combined DNA prime/replicon boost strategy show great promise for valid RVFV vaccine development. The combined approach included plasmid vaccinations at Weeks 0 and 3 followed by a replicon boost at Week 6.