Immune responses and protection induced by DNA vaccines encoding bovine parainfluenza virus type 3 glycoproteins

This study was designed to assess the parameters influencing the magnitude and type of immune responses generated to plasmids encoding the hemagglutin in/neuraminidase (HN) and fusion (F) proteins of bovine parainfluenzavirus type 3 (BPIV3). Mice immunized with plasmids expressing HN or F under contr ol of the Rous sarcoma virus long terminal repeat promoter were primed, but they did not develop measurable immune responses. In contrast, strong humo ral and cellular immune responses were induced with constructs containing t he human cytomegalovirus immediate-early promoter and intron A. After immun ization with both HN- and F-encoding plasmids, enhanced responses were obse rved. Analysis of in vitro protein synthesis confirmed that the presence of the intron is crucial for the expression of the BPIV3 HN gene. Plasmid enc oding HN induced significantly higher serum antibody liters by intradermal injection than by intramuscular delivery, whereas antigen-specific T cell p roliferation was stronger in intramusculary injected mice. Both the isotype ratios and the cytokine profiles indicated a Th1-type response after intra muscular immunization and a mixed to Th2-type response in intradermally imm unized mice. A plasmid encoding a truncated, secreted form of HN induced a Th2-type immune response, regardless of the route of delivery. In cotton ra ts, HN- and F-encoding plasmids conferred protection from BPIV3 challenge. (C) 1999 Academic Press.