Rapid, high-level production of hepatitis B core antigen in plant leaf and its immunogenicity in mice.
Hepatitis B core antigen (HBc or HBcAg) self-assembles into capsid particles and is extremely immunogenic. HBc has been extensively studied for its production in various expression systems and for the use of HBc particles for high-density, immunogenic presentation of foreign epitopes. Here we reported the high-level transient expression of HBc in plant leaf and its immunogenicity in mice. By using a novel plant viral expression system, HBc was produced in Nicotiana benthamiana leaves at levels up to 7.14% of total soluble protein (TSP) or 2.38 milligrams HBc per gram of fresh weight at 7 days post-infection (dpi). Plant-derived HBc (p-HBc) assembled into virus-like particles (VLPs) as revealed by sucrose gradients and electron microscopy. Partially purified p-HBc stimulated strong serum antibody responses in mice as Escherichia coli-derived HBc upon intraperitoneal (i.p.) injection. Furthermore, mice immunized mucosally (orally and intranasally) with p-HBc in the absence of adjuvants also developed HBc-specific serum IgG as well as intestinal IgA. Taken together, our results indicate the potential usefulness of p-HBc-VLP as a carrier for immunogenic presentation and mucosal delivery of foreign epitopes.
Huang
Zhong
Z
Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ 85287-5401, USA. Zhong.Huang@asu.edu
Santi
Luca
L
LePore
Kate
K
Kilbourne
Jacquelyn
J
Arntzen
Charles J
CJ
Mason
Hugh S
HS
D000818:Animals; D000917:Antibody Formation; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006512:Hepatitis B Core Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006515:Hepatitis B virus / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D018515:Plant Leaves / Q000235:genetics / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000276:immunology
D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D014614:Vaccines, Synthetic