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

Streptococcus pneumoniae is a leading cause of morbidity and mortality in b oth the developing and developed world. The T-independent nature of the cur rent polysaccharide vaccine renders it ineffective in elderly adults and ch ildren < 2 years of age. Although the recently licensed conjugate vaccines are capable of producing T-cell-dependent immunity, they also have their li mitations, namely a lack of response in certain populations. Our laboratory has focused on a different approach. DNA vaccination. We have defined a pe ptide 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 t o immunize mice. We have shown by ELISA that this peptide mimic is capable of eliciting an anti-PPS4 immune response significantly higher than in nega tive control mice (P < 0.05). A PPS4-DNA vaccine was made by cloning an oli godeoxynucleotide 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 D NA vector (P < 0.05). Our results demonstrate the feasibility of peptide mi micry in DNA vaccine development. (C) 2001 Elsevier Science Ltd. All rights reserved.