title: Baculovirus vector as an avian influenza vaccine: hemagglutinin expression and presentation augment the vaccine immunogenicity.
abstract: Baculovirus simultaneously displaying and expressing the avian influenza virus (AIV) hemagglutinin (HA) protein can induce potent anti-HA humoral and cellular immune responses. Based on the hypothesis that improving the antigen expression and presentation can further boost the AIV vaccine efficacies, we first constructed a baculoviral vector (Bac-HAW) with HA gene fused with the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) near its 3' end and expressed under the control of the hybrid CAG promoter. The WPRE fusion improved the HA expression and augmented the humoral and Th1 cellular immune responses after intramuscular administration into BALB/c mice. With Bac-HAW as the backbone, we next constructed Bac-HAMW which harbored the HA gene flanked with the signal sequence (MHCIss) and trafficking domain (MITD) of MHC class I molecule. In comparison with Bac-HAW, Bac-HAMW ameliorated the HA peptide presentation, significantly elevated the HA-specific humoral response (total IgG, IgG2a and hemagglutination inhibition titers) and favorably boosted the Th1 and IFN-γ(+)/CD8(+) T cell responses without extraneous adjuvants. These data collectively confirmed that enhancement of antigen expression and presentation by combining the WPRE and MHCIss/MITD fusion can potentiate the immunogenicity of the baculovirus-based vaccine, and implicates the potential of Bac-HAMW as an appealing AIV vaccine.
authors: Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors: Chi-Yuan
authors: CY
authors: Chen
authors: Shih-Yeh
authors: SY
authors: Lin
authors: Ming-Chu
authors: MC
authors: Cheng
authors: Ching-Ping
authors: CP
authors: Tsai
authors: Chang-Lin
authors: CL
authors: Hung
authors: Kai-Wei
authors: KW
authors: Lo
authors: Yung
authors: Y
authors: Hwang
authors: Yu-Chen
authors: YC
authors: Hu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016367:Baculoviridae / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma