Long-term Protection in Hamsters against Human Parainfluenza Virus Type 3 Following Mucosal or Combinations of Mucosal and Systemic Immunizations with Chimeric Alphavirus-based Replicon Particles

No licensed vaccines are available to protect against parainfluenza virus type 3 (PIV3), a significant health risk for infants. In search of a safe vaccine, we used an alphavirus-based chimeric vector, consisting of Sindbis virus (SIN) structural proteins and Venezuelan equine encephalitis virus (VEE) replicon RNA, expressing the PIV3 hemagglutinin-neuraminidase (HN) glycoprotein (VEE/SIN-HN). We compared different routes of intramuscular (IM), intranasal (IN), or combined IN and IM immunizations with VEE/SIN-HN in hamsters. Six months after the final immunization, all hamsters were protected against live PIV3 IN challenge in nasal turbinates and lungs. This protection appeared to correlate with antibodies in serum, nasal turbinates and lungs. This is the first report demonstrating mucosal protection against PIV3 for an extended time following immunizations with an RNA replicon delivery system.