MVA-based vaccines are protective against lethal eastern equine encephalitis virus aerosol challenge in cynomolgus macaques

Abstract

MVA-based monovalent eastern equine encephalitis virus (MVA-BN-EEEV) and multivalent western, eastern, and Venezuelan equine encephalitis virus (MVA-BN-WEV) vaccines were evaluated in the cynomolgus macaque aerosol model of EEEV infection. Macaques vaccinated with two doses of 5 × 108 infectious units of the MVA-BN-EEEV or MVA-BN-WEV vaccine by the intramuscular route rapidly developed robust levels of neutralizing antibodies to EEEV that persisted at high levels until challenge at day 84 via small particle aerosol delivery with a target inhaled dose of 107 PFU of EEEV FL93-939. Robust protection was observed, with 7/8 animals receiving MVA-BN-EEEV and 100% (8/8) animals receiving MVA-BN-WEV surviving while only 2/8 mock vaccinated controls survived lethal challenge. Complete protection from viremia was afforded by both vaccines, with near complete protection from vRNA loads in tissues and any pathologic evidence of central nervous system damage. Overall, the results indicate both vaccines are effective in eliciting an immune response that is consistent with protection from aerosolized EEEV-induced disease.

Syrian Hamsters Model Does Not Reflect Human-like Disease after Aerosol Exposure to Encephalitic Alphaviruses

“…Similar to the VEEV-infected hamsters, the EEEV-infected hamsters ( Table 1 and Table 2 ; Figure 6 ) had extensive necrosis and hemorrhaging in the intestines. The necrosis of the intestines along with the short survival time of the hamsters ( Figure 1 ) make them an undesirable model for therapeutic studies, especially since mice [ 39 , 41 , 46 , 61 ] and NHPs [ 45 , 46 , 47 , 62 , 63 ] have a longer therapeutic window for treatment. The rapid onset of WEEV disease in the hamsters, similar to EEEV, results in a very short therapeutic window for medical countermeasure development that is not observed in the NHP model [ 13 , 46 , 47 ].…”