A DNA vaccine encoding a peptide mimic of Streptococcus pneumoniae serotype 4 capsular polysaccharide induces specific anti-carbohydrate antibodies in Balb/c mice

被引:58
作者
Lesinski, GB
Smithson, SL
Srivastava, N
Chen, DX
Widera, G
Westerink, MAJ
机构
[1] Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA
[2] Med Coll Ohio, Dept Med, Toledo, OH 43614 USA
[3] Powderject Vaccines Inc, Madison, WI 53711 USA
关键词
DNA vaccines; peptide mimicry; Streptococcus pneumoniae;
D O I
10.1016/S0264-410X(00)00397-2
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Streptococcus pneumoniae is a leading cause of morbidity and mortality in both the developing and developed world. The T-independent nature of the current polysaccharide vaccine renders it ineffective in elderly adults and children < 2 years of age. Although the recently licensed conjugate vaccines are capable of producing T-cell-dependent immunity, they also have their limitations, namely a lack of response in certain populations. Our laboratory has focused on a different approach. DNA vaccination. We have defined a peptide sequence (pep4) that mimics the S. pnc pneumoniae serotype 4 capsular polysaccharide (PPS4) using a monoclonal antibody to PPS4 (mAb4) and phage display library. Pep4 was synthesized, complexed to proteosomes and used to immunize mice. We have shown by ELISA that this peptide mimic is capable of eliciting an anti-PPS4 immune response significantly higher than in negative control mice (P < 0.05). A PPS4-DNA vaccine was made by cloning an oligodeoxynucleotide encoding pep4 into thr HBcAg vector. Following epidermal immunization with the PPS4-DNA vaccine, mice produced an anti-PPS4 antibody response significantly higher than in mice immunized with an impertinent DNA vector (P < 0.05). Our results demonstrate the feasibility of peptide mimicry in DNA vaccine development. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1717 / 1726
页数:10
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