title: A DNA vaccine encoding a peptide mimic of Streptococcus pneumoniae serotype 4 capsular polysaccharide induces specific anti-carbohydrate antibodies in Balb/c mice.
abstract: 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. 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 the 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.
authors.affiliation: Department of Pathology, Medical College of Ohio, 3055 Arlington Avenue, 43614, Toledo, OH, USA
authors.forename: G B
authors.initials: GB
authors.lastname: Lesinski
authors.forename: S L
authors.initials: SL
authors.lastname: Smithson
authors.forename: N
authors.initials: N
authors.lastname: Srivastava
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Widera
authors.forename: M A
authors.initials: MA
authors.lastname: Westerink
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000915:Antibody Affinity; D000918:Antibody Specificity / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D018716:Molecular Mimicry / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D022242:Pneumococcal Vaccines / Q000235:genetics / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D019151:Peptide Library; D010455:Peptides; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D019444:Vaccines, DNA