TY - JOUR
T1 - Immune responses and protection induced by DNA vaccines encoding bovine parainfluenza virus type 3 glycoproteins
AU - Van Drunen Littel-van Den Hurk, S.
AU - Braun, R. P.
AU - Karvonen, B. C.
AU - King, T.
AU - Yoo, D.
AU - Babiuk, L. A.
N1 - Funding Information:
The authors are grateful to Laura Latimer for technical assistance and to the animal support staff at VIDO for care and handling of the animals. We thank Dr. M. Baca-Estrada for helpful discussion and antibodies specific for cotton rat IgA. Financial support was provided by the Natural Science and Engineering Research Council of Canada, Medical Research Council, Beef Industry Development Fund, Alberta Agricultural Research Institute, Alberta Cattle Commission, and Agricultural Development Fund.
PY - 1999/7/20
Y1 - 1999/7/20
N2 - This study was designed to assess the parameters influencing the magnitude and type of immune responses generated to plasmids encoding the hemagglutinin/neuraminidase (HN) and fusion (F) proteins of bovine parainfluenzavirus type 3 (BPIV3). Mice immunized with plasmids expressing HN or F under control of the Rous sarcoma virus long terminal repeat promoter were primed, but they did not develop measurable immune responses. In contrast, strong humoral and cellular immune responses were induced with constructs containing the human cytomegalovirus immediate-early promoter and intron A. After immunization with both HN- and F-encoding plasmids, enhanced responses were observed. Analysis of in vitro protein synthesis confirmed that the presence of the intron is crucial for the expression of the BPIV3 HN gene. Plasmid encoding HN induced significantly higher serum antibody titers by intradermal injection than by intramuscular delivery, whereas antigen- specific T cell proliferation was stronger in intramuscularly injected mice. Both the isotype ratios and the cytokine profiles indicated a Th1-type response after intramuscular immunization and a mixed to Th2-type response in intradermally immunized mice. A plasmid encoding a truncated, secreted form of HN induced a Th2-type immune response, regardless of the route of delivery. In cotton rats, HN- and F-encoding plasmids conferred protection from BPIV3 challenge.
AB - This study was designed to assess the parameters influencing the magnitude and type of immune responses generated to plasmids encoding the hemagglutinin/neuraminidase (HN) and fusion (F) proteins of bovine parainfluenzavirus type 3 (BPIV3). Mice immunized with plasmids expressing HN or F under control of the Rous sarcoma virus long terminal repeat promoter were primed, but they did not develop measurable immune responses. In contrast, strong humoral and cellular immune responses were induced with constructs containing the human cytomegalovirus immediate-early promoter and intron A. After immunization with both HN- and F-encoding plasmids, enhanced responses were observed. Analysis of in vitro protein synthesis confirmed that the presence of the intron is crucial for the expression of the BPIV3 HN gene. Plasmid encoding HN induced significantly higher serum antibody titers by intradermal injection than by intramuscular delivery, whereas antigen- specific T cell proliferation was stronger in intramuscularly injected mice. Both the isotype ratios and the cytokine profiles indicated a Th1-type response after intramuscular immunization and a mixed to Th2-type response in intradermally immunized mice. A plasmid encoding a truncated, secreted form of HN induced a Th2-type immune response, regardless of the route of delivery. In cotton rats, HN- and F-encoding plasmids conferred protection from BPIV3 challenge.
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U2 - 10.1006/viro.1999.9793
DO - 10.1006/viro.1999.9793
M3 - Article
C2 - 10405354
AN - SCOPUS:0343036542
SN - 0042-6822
VL - 260
SP - 35
EP - 46
JO - Virology
JF - Virology
IS - 1
ER -