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Abstract
Parainfluenza virus 5 (PIV5) has been used as a viral vector for vaccine development for a multitude of viral vaccines including influenza A virus (IAV), rabies virus (RABV), and respiratory syncytial virus (RSV). Apart from being an excellent vector for viral vaccines, PIV5 has also been proven to work as a platform for bacterial vaccines, yielding efficacious vaccines against Burkholderia mallei and Burkholderia pseudomallei, two highly pathogenic bacteria that cause glanders and melioidosis respectively. To further improve the PIV5-based B. mallei and B. pseudomallei, we investigated the role of the novel antigen peptidoglycan- associated lipoprotein (Pal) from B. mallei both in vitro and in vivo as well as generated a PIV5-based vaccine expressing this protein (PIV5-PalBm). Our results demonstrate that the Pal protein is involved in pathogenesis of B. mallei. We also show that a single dose of the PIV5-PalBm vaccine is protective in a mouse model of aerosol infection. In addition, we discovered that the efficacy of the vaccine can be enhanced when given in combination with other PIV5-based vaccine candidates expressing B. mallei antigens as a bivalent or trivalent vaccine, or with live-attenuated or inactivated bacteria.As an alternative for live viral vectored vaccines, our lab has also developed an amplifying virus-like particle (AVLP) vaccine platform based on PIV5, which allows amplifying of a gene of interest in cells without producing PIV5 progeny. We evaluated the potential of the PIV5-based AVLP system as a vaccine platform using respiratory syncytial virus (RSV) as our model, the most common cause of lower respiratory tract infections in children under one year of age. Our results demonstrate that an AVLP-based vaccine expressing either RSV F (AVLP-F) or RSV M2-1 (AVLP-M2-1) protein is protective against RSV challenge in mice. More importantly we discovered that the AVLP vaccine platform can induce more robust cellular immune responses compared to live PIV5 vaccines. The results of these studies highlight the potential of PIV5 and the PIV5-based AVLP system as platforms for vaccine development.