YEAST EXPRESSING HEPATITIS-B VIRUS SURFACE-ANTIGEN DETERMINANTS ON ITS SURFACE - IMPLICATIONS FOR A POSSIBLE ORAL VACCINE

The two major hydrophilic regions of the hepatitis B virus surface ant igen (HBsAg) have been expressed in the outer mannoprotein layer of th e cell wall of ''Bakers Yeast'', Saccharomyces cerevisiae, by fusing t hem between the yeast invertase signal sequence and the yeast alpha-ag glutinin carboxyterminal cell wall anchoring sequence. The fusion prot ein contained most of the preS sequences, including the hepatocyte rec eptor, and part of the S sequence including the ''a'' determinant, and was expressed fr om multiple genomic copies (MIRY) using the constitu tive PCK promoter. Immunofluorescence studies showed that the fusion p rotein 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 agains t yeast itself. If is proposed that increasing the amount of the antig en 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. Copyrig ht (C) 1996 Elsevier Science Ltd.