Abstract
We investigated whether immunization with recombinant anti-idiotypic antibody fragments mimicking the conformation of the capsular antigen can protect against infection by group B streptococcus, an important neonatal pathogen. Single-chain fragment-variable anti-idiotypes competed with the type III carbohydrate for binding to type-specific antibodies and elicited, in mice, the production of protective immunoglobulins reacting against the type III polysaccharide. Moreover, maternal immunization with soluble or phage-displayed fragments protected neonatal mice against streptococcal infection. These data indicate that recombinant anti-idiotypic antibodies may be useful in developing protein images of relevant carbohydrate epitopes and, ultimately, in preventing infections by encapsulated bacteria.
Similar content being viewed by others
Article PDF
References
Baker, C.J. & Edwards, M.S. In Infectious Diseases of the Fetus and Newborn Infant (eds. Remington, J. & Klein, J.O.) 980–1054 (W.B. Saunders,–Philadelphia, PA 1995).
Rubens, C.E., Wessels, M.R., Heggen, L.M. & Kasper, D.L. Transposon mutagenesis of group B streptococcal type III capsular polysaccharide: correlation of capsule expression with virulence. Proc. Natl. Acad. Sci. USA 84, 7208–7212 (1987).
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 68, 544–549 (1981).
Baker, C.J. & Kasper, D.L. Correlation of maternal antibody deficiency with susceptibility to neonatal group B streptococcal infection. N. Engl. J. Med. 294, 753–756 (1976).
Baker, C.J. et al. Immunization of pregnant women with a polysaccharide vaccine of group B Streptococcus. N. Engl. J. Med. 319, 1180–1185 (1988).
McLeod Griffiss, J., Apicella, M.A., Greenwood, B. & Makela, P.H. Vaccines against encapsulated bacteria: a global agenda. Rev. Infect. Dis. 9, 176–181 (1987).
Molecular and Clinical Aspects of Bacterial Vaccine Development (eds. Ala'Aldeen, D.A.A. & Hormaeche, C.E.) (John Wiley & Sons, Chichester, UK, 1995).
Lagergärd, 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. 58, 687–694 (1990).
Paoletti, L.C. et al. Neonatal mouse protection against infection with multiple group B streptococcal (GBS) serotypes by maternal immunization with a tetravalent GBS polysaccharide-tetanus toxoid conjugate vaccine. Infect. Immun. 62, 3236–3243 (1994).
Kasper, D.L. et al. Immune response to type III streptococcal polysaccharide-tetanus toxoid conjugate vaccine. J. Clin. Invest. 98, 2308–2314 (1996).
Paoletti, L.C., Kennedy, R.C., Chanh, T.C. & Kasper, D.L. Immunogenicity of group B Streptococcus type III polysaccharide-tetanus toxoid vaccine in baboons. Infect. Immun. 64, 677–679 (1996).
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. 60, 4989–4994 (1992).
Larsonn, C., Ståhammar-Carlemalm, M. & Lindahl, G. Experimental vaccination against group B streptococcus, an encapsulated bacterium, with higly purified preparations of cell surface proteins rib and a. Infect. Immun. 64, 3518–3523 (1996).
Westerink, M.A.J., Giardina, P.C., Apicella, M.A. & Kieber-Emmons, T. Peptide mimicry of the meningococcal group C capsular polysaccharide. Proc. Natl. Acad. Sci. USA 92, 4021–4025 (1995).
Agadjanyan, M. et al. Peptide mimicry of carbohydrate epitopes on human immunodeficiency virus. Nature Biotechnol. 15, 547–551 (1997).
Westerink, M.A., Muller, E. & Apicella, M.A. In Idiotypic network and disease (eds. Cerney, J. & Hiernaux, J.) 107–119 (American Society for Microbiology, Washington, DC 1990).
McNamara, M., Ward, R.E. & Kohler, I.J. Monoclonal idiotype vaccine against Streptococcus pneumoniae infection. Science 226, 1325–1326 (1984).
Stein, K.E. & Soderstrom, T. Neonatal administration of idiotype or anti-idiotype primes for protection against E. coli K13 infection in mice. J. Exp. Med. 160, 1001–1041 (1984).
Westerink, M.A., Campagnari, A.A., Wirth, M.A. & Apicella, M.A. Development and characterization of an anti-idiotype antibody to the capsular polysaccharide of Neisseria meningitidis serogroup C. Infect. Immun. 56, 1120–1127 (1988).
Magliani, W. et al. Therapeutic potential of anti-idiotypic single chain antibodies with yeast killer toxin activity. Nature Biotechnol. 15, 155–158 (1997).
Teti, G. et al. Specificity and protective activity of murine monoclonal antibodies directed against the capsular polysaccharide of type III group B streptococci. Hybridoma 11, 13–22 (1992).
Wessels, M.R., Haft, R.F., Heggen, L.M. & Rubens, C.E. Identification of a genetic locus essential for capsule sialation in type III group B streptococci. Infect. Immun. 60, 392–400 (1992).
Finne, J., Leinoen, M. & Makela, P.H. Antigenic similarities between brain components and bacteria causing meningitis. Implications for vaccine development and pathogenesis. Lancet, 11, 355–357 (1983).
Frasch, C.E. Vaccines for prevention of meningococcal disease. Clin. Microbiol. Rev. 2, S134–S138 (1989).
Kortt, A.A. et al. Recombinant antineuraminidase single chain Fv antibody: characterization, formation of dimer and higher molecular mass multimers and the solution of the crystal structure of the scFv-neuraminidase complex. Eur.J. Immunol. 23, 206–211 (1994).
Gherardi, E. & Milstein, C. Original and artificial antibodies. Nature 357, 201–202 (1992).
Teti, G., Tomasello, F. & Mancuso, G. Synthesis and immunological properties of an O-stearoyl polysaccharide from group B streptococci. J. Immunol. Res. 4, 67–72 (1992).
Mancuso, G., Tomasello, F. von Hünolstein, C., Orefici, G. & Teti, G. Induction of tumor necrosis factor alpha by the group- and type-specific polysaccharides from type III group B streptococci. Infect. Immun. 62, 2748–2753 (1994).
Aminoff, D. Methods for the quantitative estimation of N-acetylneuramic acid and their applications to hydrolisates of sialomucoids. Biochem. J. 81, 384–390 (1961).
Dische, Z. & Shettles, R.B. A specific color reaction of methylpentoses and a spectrophotometric micromethod for their determination. J. Biol. Chem. 17, 595–599 (1948).
Teti, G., Mancuso, G. & Tomasello, F. Cytokine appearance and effects of anti-tumor necrosis factor antibodies in a neonatal rat model of group-B streptococcal infection. Infect. Immun. 61, 227–235 (1993).
Mancuso, G. et al. Beneficial effects of interleukin 6 in neonatal mouse models of group B streptococcal disease. Infect. Immun. 62, 4997–5002 (1994).
Cusumano, V. et al. Role of gamma interferon in a neonatal mouse model of group B streptococcal disease. Infect. Immun. 64, 2941–2944 (1996).
Mancuso, G. et al. Role of interleukin 12 in experimental neonatal sepsis caused by group B streptococci. Infect. Immun. 65, 3731–3735 (1997).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Magliani, W., Polonelli, L., Conti, S. et al. Neonatal mouse immunity against group B streptococcal infection by maternal vaccination with recombinant anti-idiotypes. Nat Med 4, 705–709 (1998). https://doi.org/10.1038/nm0698-705
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/nm0698-705
This article is cited by
-
Protective role of IL-18 in host defenses against group B Streptococcus
European Journal of Clinical Microbiology & Infectious Diseases (2021)
-
Lambda phage nanoparticles displaying HER2-derived E75 peptide induce effective E75-CD8+ T response
Immunologic Research (2018)
-
Anti-idiotypic antibodies: a new approach in prion research
BMC Immunology (2009)
-
Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells
Nature Immunology (2009)
-
Isolation and characterisation of a human anti-idiotypic scFv used as a surrogate tumour antigen to elicit an anti-HER-2/neu humoral response in mice
British Journal of Cancer (2004)