Identification of synthetic vaccine candidates against SARS CoV infection.
Three peptides, D1 (amino acid residues 175-201), D2 (a.a. 434-467), and TM (a.a. 1128-1159), corresponding to the spike protein (S) of severe acute respiratory syndrome corona virus (SARS CoV) were synthesized and their immunological functions were investigated in three different animals models (mice, guinea pigs, and rabbits). The peptides mixture formulated either with Freund's adjuvant or synthetic adjuvant Montanide ISA-51/oligodeoxy nucleotide CpG (ISA/CpG) could elicit antisera in immunized animals which were capable of inhibiting SARS/HIV pseudovirus entry into HepG2 cells. The neutralizing epitopes were identified using peptides to block the neutralizing effect of guinea pig antisera. The major neutralizing epitope was located on the D2 peptide, and the amino acid residue was fine mapped to 434-453. In BALB/c mice T-cell proliferation assay revealed that only D2 peptide contained T-cell epitope, the sequence of which corresponded to amino acid residue 434-448. The ISA/CpG formulation generated anti-D2 IgG titer comparable to those obtained from Freund's adjuvant formulation, but generated fewer antibodies against D1 or TM peptides. The highly immunogenic D2 peptide contains both neutralizing and Th cell epitopes. These results suggest that synthetic peptide D2 would be useful as a component of SARS vaccine candidates.
Lien
Shu-Pei
SP
Vaccine Research and Development Center, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 350, Taiwan, ROC.
Shih
Yi-Ping
YP
Chen
Hsin-Wei
HW
Tsai
Jy-Ping
JP
Leng
Chih-Hsiang
CH
Lin
Min-Han
MH
Lin
Li-Hsiu
LH
Liu
Hsin-Yu
HY
Chou
Ai-Hsiang
AH
Chang
Yu-Wen
YW
Chen
Yi-Ming A
YM
Chong
Pele
P
Liu
Shih-Jen
SJ
D000818:Animals; D015195:Drug Design; D000939:Epitopes / Q000737:chemistry; D005620:Freund's Adjuvant; D006168:Guinea Pigs; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010455:Peptides / Q000737:chemistry; D011817:Rabbits; D045169:Severe Acute Respiratory Syndrome / Q000378:metabolism / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000378:metabolism; D018417:Th1 Cells; D014614:Vaccines, Synthetic / Q000737:chemistry*
D000939:Epitopes; D010455:Peptides; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D005620:Freund's Adjuvant