Protective immunity induced by phage displayed mitochondrial related peptides of Schistosoma japonicum.
New antigens and strategies are necessary for vaccine development against schistosomiasis japonica. Using a pool of 43 high titred anti-SWA sera from individuals residing in an Schistosoma japonicum endemic area of China, we have cloned a S. japonicum gene by cDNA library screening. The recombinant Sj338 protein has 44-46% identity to a mitochondrial precursor receptor protein of humans and rats. Immunization of mice with the recombinant Sj338 conferred 27-32% (p<0.01) reduction in worm burdens following cercarial challenge. In an effort to identify protective epitopes in Sj338 and increase the level of protection, we screened a random 12-mer peptide library constructed in M13 using a polyspecific anti-Sj338 rabbit serum. After five rounds of biopanning, we identified 30 reactive clones consisting of 11 distinct peptide sequences. These clones shared limited primary sequence homology with the recombinant Sj338 protein. Anti-sera raised against these phage clones recognized recombinant Sj338 and SWAP by Western blot. In murine vaccination experiments using whole recombinant phage without adjuvant, four of these clones demonstrated worm reductions of 11.6-25.1% (p=ns - 0.05) compared to M13 vaccinated animals. Animals vaccinated with all four of these phage demonstrated 34.2% (p<0.01) worm reduction compared to controls vaccinated with M13 clone. These data suggest that mimotope peptides are potential vaccine candidates for S. japonicum.
Wu
Hai-Wei
HW
Department of Pathogen Biology, Nanjing Medical University, 140 Hanzhong Rd, Nanjing, Jiangsu 210029, PR China. haiwei@njmu.edu.cn
Hu
Xue-Mei
XM
Wang
Yong
Y
Kurtis
J D
JD
Zeng
Fan-Jie
FJ
McGarvey
S T
ST
Wu
Guan-Ling
GL
Zhang
Zhao-Song
ZS
Hua
Zi-Chun
ZC
D000595:Amino Acid Sequence; D000818:Animals; D000947:Antigens, Helminth / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D007114:Immunization / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D024101:Mitochondrial Proteins / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D019151:Peptide Library; D018510:RNA, Helminth; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012549:Schistosoma japonicum / Q000235:genetics / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology* / Q000517:prevention & control*; D017422:Sequence Analysis, DNA
D000947:Antigens, Helminth; D000939:Epitopes; D024101:Mitochondrial Proteins; D019151:Peptide Library; D018510:RNA, Helminth