Recombinant Vaccine Production in Yeast - Methylotrophic yeast provide balanced production of the membrane and protein components of a recombinant viral particle. - BioPharm International

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Recombinant Vaccine Production in Yeast
Methylotrophic yeast provide balanced production of the membrane and protein components of a recombinant viral particle.


BioPharm International


The vaccine particles are harvested and cells are disrupted by a sequence of ion exchange, ultra filtration, and gel filtration steps.7 The purified HBsAg particles are formulated by adsorption to an aluminum hydroxide adjuvant and addition of a preservative. A single adult dose containing 10 or 20 g of rHBsAg may be administered in three single injections at 0, 1, and 6 months.

Outlook

In more recent developments, yeast-based HepB vaccines are modified by inclusion of alternative adjuvants, among others RC-529, a non-toxic lipid A mimetic35 or synthetic oligodeoxynucleotides containing immunostimulatory CpG motifs36 to reduce the administration schedule or to improve seroprotection. Other developments include other antigens such as large surface antigen or core protein sequences which aim to reduce the number of nonresponders or to develop a therapeutic vaccine.37 Several combination vaccines are already on the market or under development that include yeast-derived HepB particles (Table 1).

The characteristics of yeasts as safe and efficient production platforms have resulted in the development of other recombinant vaccines. An S. cerevisiae-based papillomavirus vaccine was launched in 2006 (Table 1).4 Ongoing development include, among others, vaccines against hepatitis C in H. polymorpha (Granovski, pers. commun.) or against malaria38 or Clostridium botulinum neurotoxin39 in P. pastoris.

GEORG MELMER, PHD, is the co-founder and CEO, GERD GELLISSEN, PHD, is the chief scientific officer, both at PharmedArtis GmbH, Germany, +49.241.6085.13270,
GOTTHARD KUNZE, PHD, leads a group active in yeast biotechnology at the IPK-Gatersleben, Germany.

References

1. Melmer G. Biopharmaceuticals and the industrial environment. Gellissen G, editor. In: Production of recombinant proteins. Weinheim, Germany: Wiley VCH;2005, pp. 319–359.

2. Goeddel D, et al. Direct expression in Escherichia coli of a DNA sequence coding for human growth hormone. Nature. 1979a;281:544–8.

3. Goeddel D, Kleid DG, Bolivar F. Expression in E. coli of chemically synthesized genes for human insulin. Proc Natl Acad Sci USA. 1979b; 76:106–110.

4. Cutts FT, et al. Human papillovirus and HPV vaccines: a review. Bull World Health Org. 2007; 719–726.

5. Harford N, Cabezon T, Coiau B, Delisse A-M, Rutgers T, De Wilde M. Construction and characterization of a Saccharomyces cerevisiae strain (RIT4376) expressing hepatitis B surface antigen. Postgrad Med J. 1987;63:65–70.

6. Schaefer S, Piontek M, Ahn S-J, Papendieck A, Janowicz ZA, Timmermans I, Gellissen G. Recombinant hepatitis B vaccines—disease characterization and vaccine production. Gellissen G, editor. In: Hansenula polymorpha—biology and applications. Weinheim, Germany: Wiley VCH;2002, pp. 185–210.

7. Brocke P, et al. Recombinant hepatitis B vaccines: disease characterization and vaccine production. Gellissen G, editors. In: Production of recombinant proteins. Weinheim, Germany: Wiley VCH;2000, pp. 319–359.

8. Gleeson M, Ortori S, Sudbery P. Transformation of the methylotrophic yeast Hansenula polymorpha. J Gen Microbiol. 1986; 132:3459–3465.

9. Roggenkamp R, Hansen H, Eckart M, Janowicz Z, Hollenberg C. Transformation of the methylotrophic yeast Hansenula polymorpha by autonomous replication and integration vectors. Mol Gen Genet. 1986;202:302–308.

10. Gellissen G, et al. Die methylotrophe Hefe als Expressionssystem für heterologe Proteine BioEngin. 1990;5:20–26.


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