Surface antigens vaccines

Yeast expression vectors have been among those most commonly used since the beginning of gene technology. Vectors based on baker s yeast, Saccharomyces cerevisiae, have been especially popular for robust expression of many types of recombinant proteins [90]. For instance, the first commercially available recombinant vaccine, the hepatitis B surface antigen vaccine, was produced from an S. cerevisiae vector [91]. Many other recombinant proteins have also been efficiently expressed in yeast including al-Antitrypsin [92], insulin [93], Epstein-Barr virus envelope protein [94], superoxide dismutase [95] and interferon-a [90]. 

Davis, H.L., Michel, M.L., Mancini, M., Schleef, M. and Whalen, R.G. (1994) Direct gene transfer in skeletal muscle plasmid DNA-based immunization against the hepatitis B virus surface antigen. Vaccine, 12, 1503-1509. 

Biopharmaceuticals that are industrially produced by microbial (bacterial or yeast) fermentation include insulin, human growth hormone, hepatitis B surface antigen vaccine, alpha interferon, beta interferon, gamma interferon, granulocyte colony stimulating factor, and interleukin-2. Table 30.8 lists some of the major biopharma products, some of which are produced by mammalian cell culture. 

Watanabe K, Kobayashi H, Kajiyama K, Morita M, Yasuda A, Gotoh H, Saeki S, Sugimoto M, Saito H, Kojima A. Improved recombinant LC16m0 or LC16m8 vaccinia virus successfully expressing hepatitis B surface antigen. Vaccine 1989 7(l) 53-9. 

Yeast is the third expression system used to produce biopharmaceuticals. As mammalian systems, they possess the ability to cany out post-translational modifications of proteins, although the glycosylation pattern usually varies somewhat from the patterns observed on the native protein or on the protein expressed in mammalian cells. Two recombinant proteins expressed in Saccharomyces cerevisiae are now approved for general medical use hepatitis B surface antigen vaccine and the anticoagulant Hirudin . Alternative promising production systems, in particular transgenic animal and plant systems, are still in development but these systems have to prove that they are technically and economically attractive. 

Verweij WR. de Haan L, Holtrop M et aL Mucosal immunoadjuvant activity of recombinant Escherichia coli heat-labile enterotoxin and its B subunit induction of systemic IgG and secretory IgA responses in mice by intranasal immunization with influenza virus surface antigen. Vaccine 1998 16(20) 2069-2076. 

Vaccines Human hepatitis B surface antigen vaccine... 

Vaccines can be roughly categorized into killed vaccines and Hve vaccines. A killed vaccine can be (/) an inactivated, whole microorganism such as pertussis, (2) an inactivated toxin, called toxoid, such as diphtheria toxoid, or (J) one or more components of the microorganism commonly referred to as subunit vaccines. The examples are capsular polysaccharide of Streptococcus pneumoniae and the surface antigen protein for Hepatitis B vims vaccine. 

Hepatitis B surface antigen Monomer has 226 amino acids Yeast Mammalian cells Vaccination Approved for sale Monomer self-assembles into structure resembling virus particles... 

Hepatitis B vaccine is manufactured using recombinant DNA technology to express hepatitis B surface antigen (HBsAg) in yeast. This is further purified with biochemical separation techniques to produce the vaccine. The vaccines are formulated to contain 10 to 40 meg of HBsAg protein/mL. Hepatitis B vaccine is available as a single component or in combination vaccines. 

Hepatitis B surface antigen (HBsAg) Tobacco leaf Mice vaccinated parenterally produced all IgG subclasses and IgM. - 3,56... 

Table 13.8 Some vaccine preparations that consist not of intact attenuated/ inactivated pathogen, but of surface antigens derived from such pathogens...

Production of subunit vaccine in an unlimited supply. Previously, production of some vaccines was limited by supply of raw material (e.g. hepatitis B surface antigen see below). 

A number of such recombinant (subunit) vaccines have now been approved for general medical use (Table 13.9). The first such product was that of hepatitis B surface antigen (rHBsAg), which gained marketing approval from the FDA in 1986. Two billion people are infected with hepatitis B worldwide, 350 million individuals suffer from life-long chronic infection, and more... 

Triacelluvax (combination vaccine containing r(modified) pertussis toxin Hepacare (r S, pre-S and pre-S2 hepatitis B surface antigens, produced in a mammalian (murine) cell line)... 

Engerix B (tradename) is a subunit vaccine containing purified recombinant hepatitis B surface antigen (HBsAg) that gained approval in the USA in 1998. It is indicated for active immunization against infection caused by all known serotypes of hepatitis B virus. 

Vaccine vector now expressing pathogen surface antigen... 

Twinrix is a vaccine combining hepatitis A virus units and hepatitis B surface antigen, thereby protecting against hepatitis A and B. 

The first system used to produce vaccines was potato plants and transgenic tubers have being employed in some clinical trials. Expression of vaccines is also reported in other hosts such as tomato, banana, carrot, lettuce, maize, alfalfa, white clover and Arabidospis. Hepatitis B surface antigen was successfully expressed in cherry tomatillo and potato. Expression of human cholera toxin p subunit was achieved in tomato and tobacco plants. ... 

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