Abstract
Most cases of neonatal sepsis and meningitis caused by group B streptococci (GBS) are attributable to one of four major capsular serotypes: Ia, Ib, II, or III. Because resistance to infection with GBS has been correlated with the presence of serum antibodies to the type-specific capsular polysaccharides in both experimental animals and human neonates, efforts have been made to elicit protective immunity with GBS capsular polysaccharide vaccines. However, the GBS capsular polysaccharides alone are not highly immunogenic in either animals or human volunteers. Therefore, we and other investigators have attempted to enhance immunogenicity by coupling individual capsular polysaccharides to a carrier protein. Here we report the synthesis and immunogenicity in rabbits of a GBS type Ib polysaccharide-tetanus toxoid vaccine prepared by the direct, covalent attachment of tetanus toxoid to a selected number of sialic acid residues on the type-specific polysaccharide. In addition, the Ib polysaccharide-tetanus toxoid conjugate vaccine was combined with similar tetanus toxoid conjugates of GBS type Ia, II, and III polysaccharides to form a tetravalent GBS conjugate vaccine. Protective efficacy of the GBS tetravalent conjugate vaccine was demonstrated in a mouse maternal immunization-neonatal challenge model of GBS infection. The results support testing in human subjects of a multivalent GBS conjugate vaccine of this design, with the eventual goal of protecting newborns against GBS infection.
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- Anthony B. F. Immunity to the group B streptococci: interaction of serum and macrophages with types Ia, Ib, and Ic. J Exp Med. 1976 May 1;143(5):1186–1198. doi: 10.1084/jem.143.5.1186. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baker C. J., Edwards M. S., Kasper D. L. Role of antibody to native type III polysaccharide of group B Streptococcus in infant infection. Pediatrics. 1981 Oct;68(4):544–549. [PubMed] [Google Scholar]
- Baker C. J., Kasper D. L. Correlation of maternal antibody deficiency with susceptibility to neonatal group B streptococcal infection. N Engl J Med. 1976 Apr 1;294(14):753–756. doi: 10.1056/NEJM197604012941404. [DOI] [PubMed] [Google Scholar]
- Baker C. J., Kasper D. L. Group B streptococcal vaccines. Rev Infect Dis. 1985 Jul-Aug;7(4):458–467. doi: 10.1093/clinids/7.4.458. [DOI] [PubMed] [Google Scholar]
- Baker C. J., Rench M. A., Edwards M. S., Carpenter R. J., Hays B. M., Kasper D. L. Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus. N Engl J Med. 1988 Nov 3;319(18):1180–1185. doi: 10.1056/NEJM198811033191802. [DOI] [PubMed] [Google Scholar]
- Baltimore R. S., Baker C. J., Kasper D. L. Antibody to group B Streptococcus type III in human sera measured by a mouse protection test. Infect Immun. 1981 Apr;32(1):56–61. doi: 10.1128/iai.32.1.56-61.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baltimore R. S., Kasper D. L., Baker C. J., Goroff D. K. Antigenic specificity of opsonophagocytic antibodies in rabbit anti-sera to group B streptococci. J Immunol. 1977 Feb;118(2):673–678. [PubMed] [Google Scholar]
- Boyer K. M., Kendall L. S., Papierniak C. K., Klegerman M. E., Gotoff S. P. Protective levels of human immunoglobulin G antibody to group B streptococcus type Ib. Infect Immun. 1984 Sep;45(3):618–624. doi: 10.1128/iai.45.3.618-624.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edwards M. S., Baker C. J., Kasper D. L. Opsonic specificity of human antibody to the type III polysaccharide of group B Streptococcus. J Infect Dis. 1979 Dec;140(6):1004–1008. doi: 10.1093/infdis/140.6.1004. [DOI] [PubMed] [Google Scholar]
- Farley M. M., Harvey R. C., Stull T., Smith J. D., Schuchat A., Wenger J. D., Stephens D. S. A population-based assessment of invasive disease due to group B Streptococcus in nonpregnant adults. N Engl J Med. 1993 Jun 24;328(25):1807–1811. doi: 10.1056/NEJM199306243282503. [DOI] [PubMed] [Google Scholar]
- Givner L. B., Edwards M. S., Baker C. J. A polyclonal human IgG preparation hyperimmune for type III, group B Streptococcus: in vitro opsonophagocytic activity and efficacy in experimental models. J Infect Dis. 1988 Oct;158(4):724–730. doi: 10.1093/infdis/158.4.724. [DOI] [PubMed] [Google Scholar]
- Gray B. M. ELISA methodology for polysaccharide antigens: protein coupling of polysaccharides for adsorption to plastic tubes. J Immunol Methods. 1979;28(1-2):187–192. doi: 10.1016/0022-1759(79)90340-5. [DOI] [PubMed] [Google Scholar]
- Greenberg D. N., Ascher D. P., Yoder B. A., Heiman H. S., Keith J. F., 3rd Group B streptococcus serotype V. J Pediatr. 1993 Sep;123(3):494–495. doi: 10.1016/s0022-3476(05)81778-0. [DOI] [PubMed] [Google Scholar]
- Heiman H. S., Weisman L. E. Transplacental or enteral transfer of maternal immunization-induced antibody protects suckling rats from type III group B streptococcal infection. Pediatr Res. 1989 Dec;26(6):629–632. doi: 10.1203/00006450-198912000-00023. [DOI] [PubMed] [Google Scholar]
- Hervás J. A., González L., Gil J., Paoletti L. C., Madoff L. C., Benedí V. J. Neonatal group B streptococcal infection in Mallorca, Spain. Clin Infect Dis. 1993 May;16(5):714–718. doi: 10.1093/clind/16.5.714. [DOI] [PubMed] [Google Scholar]
- Jennings H. J., Katzenellenbogen E., Lugowski C., Kasper D. L. Structure of native polysaccharide antigens of type Ia and type Ib group B Streptococcus. Biochemistry. 1983 Mar 1;22(5):1258–1264. doi: 10.1021/bi00274a042. [DOI] [PubMed] [Google Scholar]
- Jennings H. J., Rosell K. G., Katzenellenbogen E., Kasper D. L. Structural determination of the capsular polysaccharide antigen of type II group B Streptococcus. J Biol Chem. 1983 Feb 10;258(3):1793–1798. [PubMed] [Google Scholar]
- Lagergard T., Shiloach J., Robbins J. B., Schneerson R. Synthesis and immunological properties of conjugates composed of group B streptococcus type III capsular polysaccharide covalently bound to tetanus toxoid. Infect Immun. 1990 Mar;58(3):687–694. doi: 10.1128/iai.58.3.687-694.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Larson E., Howlett B., Jagendorf A. Artificial reductant enhancement of the Lowry method for protein determination. Anal Biochem. 1986 Jun;155(2):243–248. doi: 10.1016/0003-2697(86)90432-x. [DOI] [PubMed] [Google Scholar]
- Madoff L. C., Michel J. L., Gong E. W., Rodewald A. K., Kasper D. L. Protection of neonatal mice from group B streptococcal infection by maternal immunization with beta C protein. Infect Immun. 1992 Dec;60(12):4989–4994. doi: 10.1128/iai.60.12.4989-4994.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paoletti L. C., Kasper D. L., Michon F., DiFabio J., Holme K., Jennings H. J., Wessels M. R. An oligosaccharide-tetanus toxoid conjugate vaccine against type III group B Streptococcus. J Biol Chem. 1990 Oct 25;265(30):18278–18283. [PubMed] [Google Scholar]
- Paoletti L. C., Kasper D. L., Michon F., DiFabio J., Jennings H. J., Tosteson T. D., Wessels M. R. Effects of chain length on the immunogenicity in rabbits of group B Streptococcus type III oligosaccharide-tetanus toxoid conjugates. J Clin Invest. 1992 Jan;89(1):203–209. doi: 10.1172/JCI115564. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paoletti L. C., Wessels M. R., Michon F., DiFabio J., Jennings H. J., Kasper D. L. Group B Streptococcus type II polysaccharide-tetanus toxoid conjugate vaccine. Infect Immun. 1992 Oct;60(10):4009–4014. doi: 10.1128/iai.60.10.4009-4014.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rench M. A., Baker C. J. Neonatal sepsis caused by a new group B streptococcal serotype. J Pediatr. 1993 Apr;122(4):638–640. doi: 10.1016/s0022-3476(05)83554-1. [DOI] [PubMed] [Google Scholar]
- Rodewald A. K., Onderdonk A. B., Warren H. B., Kasper D. L. Neonatal mouse model of group B streptococcal infection. J Infect Dis. 1992 Sep;166(3):635–639. doi: 10.1093/infdis/166.3.635. [DOI] [PubMed] [Google Scholar]
- WARREN L. The thiobarbituric acid assay of sialic acids. J Biol Chem. 1959 Aug;234(8):1971–1975. [PubMed] [Google Scholar]
- Weisman L. E., Anthony B. F., Hemming V. G., Fischer G. W. Comparison of group B streptococcal hyperimmune globulin and standard intravenously administered immune globulin in neonates. J Pediatr. 1993 Jun;122(6):929–937. doi: 10.1016/s0022-3476(09)90023-3. [DOI] [PubMed] [Google Scholar]
- Wessels M. R., Paoletti L. C., Kasper D. L., DiFabio J. L., Michon F., Holme K., Jennings H. J. Immunogenicity in animals of a polysaccharide-protein conjugate vaccine against type III group B Streptococcus. J Clin Invest. 1990 Nov;86(5):1428–1433. doi: 10.1172/JCI114858. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wessels M. R., Paoletti L. C., Rodewald A. K., Michon F., DiFabio J., Jennings H. J., Kasper D. L. Stimulation of protective antibodies against type Ia and Ib group B streptococci by a type Ia polysaccharide-tetanus toxoid conjugate vaccine. Infect Immun. 1993 Nov;61(11):4760–4766. doi: 10.1128/iai.61.11.4760-4766.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wessels M. R., Pozsgay V., Kasper D. L., Jennings H. J. Structure and immunochemistry of an oligosaccharide repeating unit of the capsular polysaccharide of type III group B Streptococcus. A revised structure for the type III group B streptococcal polysaccharide antigen. J Biol Chem. 1987 Jun 15;262(17):8262–8267. [PubMed] [Google Scholar]