The application of molecular biology to the development of novel vaccines.
In summary, we have shown that yeast is the preferred host for the expression of recombinant-derived hepatitis B vaccines, and that a yeast expression system which is productive, stable and scaleable can be developed for each of the three HBV envelope proteins. The versatility of regulated and integrated yeast expression systems in the production of foreign polypeptides with biomedical utility also has been highlighted. We also have shown that careful attention to the development of recombinant clones helps to optimize the entire production process leading to highly purified products which share many biochemical properties with the plasma-derived vaccine. Furthermore, immunization with PreS2 sequences is capable of protecting chimpanzees from HBV infection. The availability of PreS2 + S and PreS1 + PreS2 + S proteins expressed in yeast now provides the opportunity for establishing the relevance of such candidate vaccines in preventing human disease, thereby highlighting the utility of molecular biology in modern vaccine development.
Kniskern
P J
PJ
Department of Virus and Cell Biology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Hagopian
A
A
Burke
P
P
Dunn
N
N
Montgomery
D L
DL
Schultz
L D
LD
Schulman
C A
CA
Carty
C E
CE
Maigetter
R Z
RZ
Wampler
D E
DE
D000818:Animals; D000917:Antibody Formation; D004274:DNA, Recombinant; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D017325:Hepatitis B Vaccines; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014612:Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D004274:DNA, Recombinant; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D014612:Vaccines; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines; D014764:Viral Proteins