A novel technology for the production of a heterologous lipoprotein immunogen in high yield has implications for the field of vaccine design.
We have developed a novel platform technology that can express high levels of recombinant lipoproteins with intrinsic adjuvant properties. In this study, Ag473 (a lipoprotein from Neisseria meningitidis) can be produced in high yields using Escherichia coli strain C43 (DE3). After testing a non-lipoimmunogen (E3, from dengue virus) fused with different lipid signal peptides from other lipoproteins as well as Ag473 fragments of different lengths, we identified that the fusion sequence has to contain at least the N-terminal 40 residues, D1, of Ag473 to achieve high expression levels of the recombinant lipo-immunogen (rlipo-D1E3). The rlipo-D1E3 was found to elicit stronger anti-E3 and virus neutralizing antibody responses in animal studies than those from rE3 alone or rE3 formulated with alum adjuvant. These results have successfully demonstrated the merit of lipo-immunogens for novel vaccine development.
Chen
Hsin-Wei
HW
Vaccine Research and Development Center, National Health Research Institutes, Zhunan Town, Miaoli 350, Taiwan, ROC.
Liu
Shih-Jen
SJ
Liu
Hsueh-Hung
HH
Kwok
Yan
Y
Lin
Chang-Ling
CL
Lin
Li-Hsiu
LH
Chen
Mei-Yu
MY
Tsai
Jy-Ping
JP
Chang
Li-Sheng
LS
Chiu
Fang-Feng
FF
Lai
Li-wei
LW
Lian
Wei-Cheng
WC
Yang
Chiou-Ying
CY
Hsieh
Shih-Yang
SY
Chong
Pele
P
Leng
Chih-Hsiang
CH
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D015195:Drug Design; D004926:Escherichia coli / Q000235:genetics; D008074:Lipoproteins / Q000096:biosynthesis / Q000276:immunology*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000096:biosynthesis / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D014612:Vaccines / Q000096:biosynthesis*; D014614:Vaccines, Synthetic / Q000096:biosynthesis / Q000276:immunology*
D001426:Bacterial Proteins; D017931:DNA Primers; D008074:Lipoproteins; C530756:NMB1468 protein, Neisseria meningitidis; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014612:Vaccines; D014614:Vaccines, Synthetic