Protective immunity and gene expression related to pneumococcal glycoconjugate.
The immunogenicity of most polysaccharides (PSs) contained in the pneumococcal vaccine is low in children less than 2 years of age. Enhancement of immune response in early life can be induced by immunization of pneumococcal glycoconjugate as well as plasma DNA coding for cell-surface protein antigen. Pneumococcal type 19F PS conjugated with inactivated pneumolysin (Ply) induced in mice remarkable antibody responses to both type 19F PS and the protein carrier. In addition, the conjugate was administered to pregnant mice during gestation and/or lactation, and to their offspring during early infancy. When the young mice were challenged with type 19F pneumococci, the bacteria were cleared more rapidly from the blood of immunized mice than from that of the control group. The mortality rate of young mice from immunized mothers was also significantly lower than the control group. These results indicate that the effective protective immunity against pneumococcal infection can be induced in young mice by the maternal immunization with the glycoconjugate during gestation and at early infancy. Studies have been conducted to express type 19A pneumolysin gene (ply) in mammalian cells. Ply DNA was inserted into the cloning site of a vector containing CMV promoter. The recombinant plasmid DNA containing ply was transfected in human rhabdomyosarcoma cells and the gene expression was confirmed by immunoblot. Injection of mice three times 50-100 ug per dose ply DNA produced high serum levels of Ply IgG and IgM antibodies and showed rapid bacterial clearance from the blood.
Lee
C J
CJ
Center for Biologics Evaluation and Research, FDA, Bethesda, MD 20817, USA.
Li
Z M
ZM
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins; D001483:Base Sequence; D002240:Carbohydrate Sequence; D004269:DNA, Bacterial / Q000235:genetics; D015870:Gene Expression; D005798:Genes, Bacterial; D006001:Glycoconjugates / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011008:Pneumococcal Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology*; D013301:Streptolysins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D018074:Vaccines, Conjugate / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D006001:Glycoconjugates; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D013301:Streptolysins; D018074:Vaccines, Conjugate; D019444:Vaccines, DNA; C032290:plY protein, Streptococcus pneumoniae