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1.
Vaccine ; 33(25): 2881-6, 2015 Jun 09.
Article in English | MEDLINE | ID: mdl-25944300

ABSTRACT

BACKGROUND: The hepatitis B surface antigen (HBsAg) has been administered over the last 20 years as a parenteral vaccine against the hepatitis B virus (HBV). Despite high seroconversion rates, chronic infection rates are still high worldwide. Orally delivered vaccines provide a practical alternative to injected vaccines, potentially helping poorly responding populations and providing a viable alternative for populations in remote locations. Anamnestic responses are vital to establishing the efficacy of a given vaccine and have been assessed in this study using a plant-based oral delivery platform expressing HBsAg. METHODS: Long-term immunological memory was assessed in mice injected with a primary dose of Recombivax and boosted with orally-delivered HBsAg wafers, control wafers, or parenterally-delivered commercial vaccine (Recombivax). RESULTS: Mice boosted with HBsAg orally-administered wafers displayed sharp increases in mucosal IgA titers in fecal material and steep increases in serum IgA, whereas mice boosted with Recombivax showed no detectable levels of IgA in either fecal or serum samples following four boosting treatments. Long-term memory in the orally-treated mice was evidenced by sustained fecal IgA, and serum IgA, IgG, and mIU/mL over one year, while Recombivax-treated mice displayed sustained serum IgG and mIU/mL. Furthermore, sharp increases in these same antibodies were induced after re-boosting at 47 and 50 weeks post-primary injection. CONCLUSIONS: Orally-delivered vaccines can provide long-term immune responses mucosally and systemically. For sexually-transmitted diseases that can be acquired at mucosal surfaces, such as HBV, an oral delivery platform may provide added protection over a conventional parenterally administered vaccine.


Subject(s)
Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/immunology , Hepatitis B, Chronic/prevention & control , Immunity, Mucosal , Immunologic Memory , Administration, Oral , Animals , Enzyme-Linked Immunosorbent Assay , Hepatitis B Antibodies/analysis , Hepatitis B Antibodies/blood , Hepatitis B Vaccines/administration & dosage , Hepatitis B, Chronic/immunology , Immunization, Secondary , Immunoglobulin A/blood , Immunoglobulin A, Secretory/analysis , Immunoglobulin G/blood , Mice, Inbred BALB C , Vaccination/methods , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , Zea mays/genetics
2.
Vaccine ; 32(11): 1240-6, 2014 Mar 05.
Article in English | MEDLINE | ID: mdl-24486361

ABSTRACT

The hepatitis B virus continues to be a major pathogen worldwide despite the availability of an effective parenteral vaccine for over 20 years. Orally-delivered subunit vaccines produced in maize may help to alleviate the disease burden by providing a low-cost, heat-stable alternative to the parenteral vaccine. Oral subunit vaccination has been an elusive goal due to the large amounts of antigen required to induce an immunologic response when administered through the digestive tract. Here we show that high levels of HBsAg were obtained in maize grain, the grain was formed into edible wafers, and wafers were fed to mice at a concentration of approximately 300 µg/g. When these wafers were made with supercritical fluid extraction (SFE)-treated maize material, robust IgG and IgA responses in sera were observed that were comparable to the injected commercial vaccine (Recombivax(®)). In addition, all mice administered SFE wafers showed high secretory IgA titers in fecal material whereas Recombivax(®) treated mice showed no detectable titer. Increased salivary IgA titers were also detected in SFE-fed mice but not in Recombivax(®) treated mice. Wafers made from hexane-treated or full fat maize material induced immunologic responses, but fecal titers were attenuated relative to those produced by SFE-treated wafers. These responses demonstrate the feasibility of using a two-dose oral vaccine booster in the absence of an adjuvant to induce immunologic responses in both sera and at mucosal surfaces, and highlight the potential limitations of using an exclusively parenteral dosing regime.


Subject(s)
Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/immunology , Immunity, Mucosal , Plants, Genetically Modified/metabolism , Administration, Oral , Animals , Chromatography, Supercritical Fluid , Hepatitis Antibodies/blood , Hepatitis B Surface Antigens/biosynthesis , Immunoglobulin A/blood , Immunoglobulin A, Secretory/immunology , Immunoglobulin G/blood , Mice , Mice, Inbred BALB C , Vaccines, Subunit/immunology , Vaccines, Synthetic/immunology , Zea mays/genetics , Zea mays/metabolism
3.
Vaccine ; 30(19): 2937-42, 2012 Apr 19.
Article in English | MEDLINE | ID: mdl-22406456

ABSTRACT

Hepatitis B remains a major global health problem despite the availability of a safe and effective vaccine. Segments of the population lack access to or respond poorly to the parenteral vaccine, perpetuating the infection-transmission cycle. A low cost, orally delivered vaccine has the potential to alleviate many of these problems. Here we describe the expression of a bioencapsulated hepatitis B surface antigen (HBsAg) in maize and its immunogenicity, demonstrating for the first time a commercially feasible oral subunit vaccine production system for a major disease. This work surmounts previous barriers to plant-produced vaccines by expressing HBsAg at much higher levels and retaining antigen immunogenicity post-processing: factors which facilitated a robust immune response in mice without the need for an adjuvant. This method provides a practical solution to the delivery of a low-cost, stable oral vaccine.


Subject(s)
Drug Delivery Systems , Hepatitis B Surface Antigens/administration & dosage , Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/administration & dosage , Hepatitis B Vaccines/immunology , Administration, Oral , Animals , Antibodies, Viral/blood , Mice , Mice, Inbred BALB C , Vaccines, Edible/administration & dosage , Vaccines, Edible/immunology , Zea mays/genetics , Zea mays/metabolism
4.
J Control Release ; 85(1-3): 169-80, 2002 Dec 13.
Article in English | MEDLINE | ID: mdl-12480322

ABSTRACT

The use of recombinant gene technologies by the vaccine industry has revolutionized the way antigens are generated, and has provided safer, more effective means of protecting animals and humans against bacterial and viral pathogens. Viral and bacterial antigens for recombinant subunit vaccines have been produced in a variety of organisms. Transgenic plants are now recognized as legitimate sources for these proteins, especially in the developing area of oral vaccines, because antigens have been shown to be correctly processed in plants into forms that elicit immune responses when fed to animals or humans. Antigens expressed in maize (Zea mays) are particularly attractive since they can be deposited in the natural storage vessel, the corn seed, and can be conveniently delivered to any organism that consumes grain. We have previously demonstrated high level expression of the B-subunit of Escherichia coli heat-labile enterotoxin and the spike protein of swine transmissible gastroenteritis in corn, and have demonstrated that these antigens delivered in the seed elicit protective immune responses. Here we provide additional data to support the potency, efficacy, and stability of recombinant subunit vaccines delivered in maize seed.


Subject(s)
Drug Delivery Systems/veterinary , Escherichia coli Proteins , Seeds , Vaccination/veterinary , Vaccines, Synthetic/administration & dosage , Zea mays , Administration, Oral , Animals , Bacterial Toxins/administration & dosage , Bacterial Toxins/immunology , Chemistry, Pharmaceutical , Enterotoxins/administration & dosage , Enterotoxins/immunology , Escherichia coli Infections/prevention & control , Escherichia coli Infections/veterinary , Gastroenteritis, Transmissible, of Swine/prevention & control , Mice , Mice, Inbred BALB C , Plant Extracts/administration & dosage , Plant Extracts/immunology , Plants, Genetically Modified/immunology , Seeds/immunology , Seeds/microbiology , Seeds/virology , Swine , Transmissible gastroenteritis virus/immunology , Vaccines, Synthetic/immunology , Viral Proteins/administration & dosage , Viral Proteins/immunology , Zea mays/immunology
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