Characterization and evaluation of a recombinant hepatitis B vaccine expressed in yeast defective for N-linked hyperglycosylation.
The hepatitis B (HB) virus preS2 + 2 polypeptide (the M or middle envelope polypeptide) is N-glycosylated at the N4 residue of the preS2 domain when expressed in recombinant yeast. Hyperglycosylation at this amino acid residue (the addition of a large number of mannose residues to the core oligosaccharide), which occurs in common yeast strains, results in an HB vaccine with diminished immunogenicity. Hyperglycosylation can be prevented by expressing the preS2 + S polypeptide in mutant yeast strains (e.g. mnn9) which limit N-linked glycosylation to the addition of only core saccharide residues. An HB vaccine prepared from recombinant yeast expressing the non-hyperglycosylated preS2 + 2 polypeptide was of similar immunogenicity in mice to a licensed HB vaccine and was much more immunogenic in humans than the hyperglycosylated preS2 + 2 vaccine.
Department of Virus and Cell Biology, Merck Research Laboratories, West Point, PA.
P J
PJ
Kniskern
A
A
Hagopian
P
P
Burke
L D
LD
Schultz
D L
DL
Montgomery
W M
WM
Hurni
C Y
CY
Ip
C A
CA
Schulman
R Z
RZ
Maigetter
D E
DE
Wampler
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D006031:Glycosylation; D006510:Hepatitis B Antibodies / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D014614:Vaccines, Synthetic / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D014614:Vaccines, Synthetic