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Yeast expressing hepatitis B virus surface antigen determinants on its surface: Implications for a possible oral vaccine

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Author: Schreuder, M.P. · Deen, C. · Boersma, W.J.A. · Pouwels, P.H. · Klis, F.M.
Type:article
Date:1996
Institution: Gaubius Instituut TNO TNO Voeding
Source:Vaccine, 5, 14, 383-388
Identifier: 233272
doi: doi:10.1016/0264-410X(95)00206-G
Keywords: Biology · Cell wall · HBsAg · Immobilized protein · Saccharomyces cerevisiae · Surface presentation · Hepatitis b surface antigen · Hybrid protein · Recombinant hepatitis b vaccine · Controlled study · Hepatitis b · Hepatitis b virus · Intraperitoneal drug administration · Molecular cloning · Mouse · Nonhuman · Priority journal · Vaccination · Yeast · Administration, Oral · Animals · Hepatitis B Surface Antigens · Hepatitis B Vaccines · Immunization · Mice · Peptide Fragments · Saccharomyces cerevisiae · Vaccines, Synthetic

Abstract

The two major hydrophilic regions of the hepatitis B virus surface antigen (HBsAg) have been expressed in the outer mannoprotein layer of the cell wall of 'Bakers Yeast', Saccharomyces cerevisiae, by fusing them between the yeast invertase signal sequence and the yeast α-agglutinin carboxyterminal cell wall anchoring sequence. The fusion protein contained most of the preS sequences, including the hepatocyte receptor, and part of the S sequence including the 'a' determinant, and was expressed from multiple genomic copies (MIRY) using the constitutive PCK promoter. Immunofluorescence studies showed that the fusion protein was detectable at the cell surface and was stably expressed at a relatively high level. Intraperitoneal immunization of mice revealed a very weak response against the S region, and a high response against yeast itself: It is proposed that increasing the amount of the antigen and reducing the number of native cell wall proteins, might lead to a yeast that is usable as a safe and cheap live oral vaccine.