Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides.

Full Abstract

Group B Streptococcus (GBS) causes serious infection in neonates and is an important target of vaccine development. Zwitterionic polysaccharides (ZPS), obtained through chemical introduction of positive charges into anionic polysaccharides (PS) from GBS, have the ability to activate human and mouse antigen presenting cells (APCs) through toll-like receptor 2 (TLR2). To generate a polysaccharide vaccine with antigen (Ag) and adjuvant properties in one molecule, we have conjugated ZPS with a carrier protein. ZPS-glycoconjugates induce higher T-cell and Ab responses to carrier and PS, respectively, compared to control PS-glycoconjugates made with the native polysaccharide form. The increased immunogenicity of ZPS-conjugates correlates with their ability to activate dendritic cells (DCs). Moreover, protection of mothers or neonate offspring from lethal GBS challenge is better when mothers are immunized with ZPS-conjugates compared to immunization with PS-conjugates. In TLR2 knockout mice, ZPS-conjugates lose both their increased immunogenicity and protective effect after vaccination. When ZPS are coadministered as adjuvants with unconjugated tetanus toxoid (TT), they have the ability to increase the TT-specific antibody titer. In conclusion, glycoconjugates containing ZPS are potent vaccines. They target Ag to TLR2-expressing APCs and activate these APCs, leading to better T-cell priming and ultimately to higher protective Ab titers. Thus, rational chemical design can generate potent PS-adjuvants with wide application, including glycoconjugates and coadministration with unrelated protein Ags.

Author information

Author/s: Gallorini, Simona (S); Berti, Francesco (F); Mancuso, Giuseppe (G); Cozzi, Roberta (R); Tortoli, Marco (M); Volpini, Gianfranco (G); Telford, John L (JL); Beninati, Concetta (C); Maione, Domenico (D); Wack, Andreas (A);

Affiliation: Novartis Vaccines Research Center, Via Fiorentina 1, 53100 Siena, Italy.

Journal and publication information

Publication Type: Journal Article

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2009-Oct; vol 106 (issue 41) : pp 17481-6

Dates: Created 2009/10/15; Completed 2009/11/03; Revised 2009/11/06;

PMID: 19805031, status: MEDLINE (last retrieval date: 11/9/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Mice
Polysaccharides - chemistry; immunology
Streptococcal Infections - immunology
Toll-Like Receptor 2 - immunology
Vaccines, Conjugate - chemistry

Associated Chemicals: Bacterial Vaccines (0) ; Polysaccharides (0) ; TLR2 protein, human (0) ; Tlr2 protein, mouse (0) ; Toll-Like Receptor 2 (0) ; Vaccines, Conjugate (0)

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