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Clinical and Vaccine Immunology, May 2008, p. 852-858, Vol. 15, No. 5
1071-412X/08/$08.00+0     doi:10.1128/CVI.00382-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Comparison of Serum Humoral Responses Induced by Oral Immunization with the Hepatitis B Virus Core Antigen and the Cholera Toxin B Subunit{triangledown}

Katleen Broos,1 Michiel E. Janssens,1 Ine De Goeyse,1 Peter Vanlandschoot,3,{dagger} Geert Leroux-Roels,3 Dirk Geysen,2 and Yves Guisez1*

Laboratory of Plant Physiology, Department of Biology, University of Antwerp, Antwerp, Belgium,1 Department of Animal Health, Institute of Tropical Medicine Antwerp, Antwerp, Belgium,2 Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University, Ghent, Belgium3

Received 24 September 2007/ Returned for modification 5 December 2007/ Accepted 12 March 2008

The hepatitis B virus core (HBc) virus-like particle (VLP) is known as one of the most immunogenic antigens and carrier vehicles in different immunization strategies. Recent findings are suggesting the potential of the HBc VLPs as an oral immunogen. Here, we focus on the induction of serum humoral responses by oral administration of HBc VLPs in preparations substantially free of lipopolysaccharide and immunomodulating encapsidated RNA. The full-length HBc antigen was used, because the C-terminal arginine-rich tail may contribute to the immunogenicity of the antigen as the region is involved in cell surface heparan sulfate binding and internalization of the protein. Serum antibody levels and isotypes were determined following oral administration of the HBc VLPs with the perspective of using the HBc VLP as an immunostimulatory and carrier molecule for epitopes of blood-borne diseases in oral immunization vaccination strategies. Following oral administration of the HBc VLP preparations to mice, a strong serum humoral response was induced with mainly immunoglobulin G2a (IgG2a) antibodies, pointing toward a Th1 response which is essential in the control of intracellular pathogens. Intraperitoneal immunization with the HBc VLP induced a stronger, mixed Th1/Th2 response. Finally, a comparison was made with the induced serum humoral response following oral administration of the recombinant cholera toxin B pentamer, a commonly used oral immunogen. These immunizations, in contrast, induced predominantly antibodies of the IgG1 isotype, indicative of a Th2 response. These data suggest that the HBc VLP can be an interesting carrier molecule in oral vaccine development.

* Corresponding author. Mailing address: Laboratory of Plant Physiology, Department of Biology, 171 Groenenborgerlaan, Building U, 6th floor, CGB University of Antwerp, 2020 Antwerpen, Belgium. Phone: 32 3 265 3415. Fax: 32 3 265 3417. E-mail: yves.guisez{at}ua.ac.be

{triangledown} Published ahead of print on 26 March 2008.

{dagger} Present address: Ablynx NV, Technologiepark 4, B-9052 Zwijnaarde, Belgium.

Clinical and Vaccine Immunology, May 2008, p. 852-858, Vol. 15, No. 5
1071-412X/08/$08.00+0     doi:10.1128/CVI.00382-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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