Low-dose oral immunization with lyophilized tissue of herbicide-resistant lettuce expressing hepatitis B surface antigen for prototype plant-derived vaccine tablet formulation.
Efficient immunization against hepatitis B virus (HBV) and other pathogens with plant-based oral vaccines requires appropriate plant expressors and the optimization of vaccine compositions and administration protocols. Previous immunization studies were mainly based on a combination of the injection of a small surface antigen of HBV (S-HBsAg) and the feeding with raw tissue containing the antigen, supplemented with an adjuvant, and coming from plants conferring resistance to kanamycin. The objective of this study was to develop a prototype oral vaccine formula suitable for human immunization. Herbicide-resistant lettuce was engineered, stably expressing through progeny generation micrograms of S-HBsAg per g of fresh weight and formed into virus-like particles (VLPs). Lyophilized tissue containing a relatively low, 100-ng VLP-assembled antigen dose, administered only orally to mice with a long, 60-day interval between prime and boost immunizations and without exogenous adjuvant, elicited mucosal and systemic humoral anti-HBs responses at the nominally protective level. Lyophilized tissue was converted into tablets, which preserved S-HBsAg content for at least one year of room temperature storage. The results of the study provide indications on immunization methodology using a durable, efficacious, and convenient plant-derived prototype oral vaccine against hepatitis B.
Institute of Plant Genetics, Polish Academy of Sciences, Strzeszyńska 34, 60-479, Poznań, Poland. tpni@igr.poznan.pl
Tomasz
T
Pniewski
Józef
J
Kapusta
Piotr
P
Bociąg
Jacek
J
Wojciechowicz
Anna
A
Kostrzak
Michał
M
Gdula
Olga
O
Fedorowicz-Strońska
Piotr
P
Wójcik
Halina
H
Otta
Sławomir
S
Samardakiewicz
Bogdan
B
Wolko
Andrzej
A
Płucienniczak
D000284:Administration, Oral; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D004721:Endoplasmic Reticulum / Q000648:ultrastructure / Q000821:virology; D005243:Feces / Q000737:chemistry; D005612:Freeze Drying; D006509:Hepatitis B / Q000517:prevention & control*; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage; D006515:Hepatitis B virus / Q000276:immunology* / Q000648:ultrastructure; D053209:Herbicide Resistance; D006540:Herbicides / Q000494:pharmacology; D006801:Humans; D056724:Immunity, Humoral; D007071:Immunoglobulin A, Secretory / Q000097:blood; D018545:Lactuca / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018515:Plant Leaves / Q000276:immunology / Q000648:ultrastructure / Q000821:virology; D030821:Plants, Genetically Modified / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology*; D014611:Vaccination; D022462:Vaccines, Edible / Q000008:administration & dosage
D000613:Aminobutyrates; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D006540:Herbicides; D007071:Immunoglobulin A, Secretory; D011994:Recombinant Proteins; D022462:Vaccines, Edible; C003121:phosphinothricin