A Synthetic Disaccharide Analogue from Neisseria meningitidis A Capsular Polysaccharide Stimulates Immune Cell Responses and Induces Immunoglobulin G (IgG) Production in Mice When Protein-Conjugated.
Some new phosphonoester-linked oligomers, stabilized analogues of the corresponding phosphate-bridged oligomers of Neisseria meningitidis A (MenA) capsular polysaccharide (CPS), were conjugated to human serum albumin (HSA), as a protein carrier model, and studied for immunological activities. We determined (i) in vitro, their biocompatibility (CAM test) and activity in inducing both T cell proliferation (CFSE method) and IL-2 release (ELISA), and (ii) in vivo, their ability to stimulate specific IgG antibody production (ELISA). All HSA-conjugated compounds induce T cell proliferation (40% of proliferation at 10(2) μM), whereas only the phosphonodisaccharide was effective (28% of proliferation at 10(2) μM) among the unconjugated forms. IL-2 release confirmed these results. In addition, the HSA-conjugated showed in vivo the capacity of eliciting the production of specific IgG antibodies. In conclusion, we obtained novel biocompatible, water-stable, and immunoactive MenA CPS analogues. A short disaccharide fragment showed the unusual behavior of triggering T cell proliferation in vitro.
Department of Pharmaceutical Sciences, University of "Piemonte Orientale, A. Avogadro" , Largo Donegani 2, 28100 Novara, Italy.
Silvia
S
Fallarini
Department of Chemistry and CRC "Materiali Polimerici" (LaMPo), University of Milan , Via Golgi 19, 20133 Milan, Italy.
Benedetta
B
Buzzi
Department of Pharmaceutical Sciences, University of "Piemonte Orientale, A. Avogadro" , Largo Donegani 2, 28100 Novara, Italy.
Sara
S
Giovarruscio
Institute of Molecular Science and Technologies, ISTM-CNR , Via G. Fantoli 16/15, 20138 Milan, Italy.
Laura
L
Polito
Novartis Vaccines and Diagnostics, Via Fiorentina 10, 53100 Siena, Italy.
Giulia
G
Brogioni
Novartis Vaccines and Diagnostics, Via Fiorentina 10, 53100 Siena, Italy.
Marta
M
Tontini
Novartis Vaccines and Diagnostics, Via Fiorentina 10, 53100 Siena, Italy.
Francesco
F
Berti
Novartis Vaccines and Diagnostics, Via Fiorentina 10, 53100 Siena, Italy.
Roberto
R
Adamo
Department of Chemistry and CRC "Materiali Polimerici" (LaMPo), University of Milan , Via Golgi 19, 20133 Milan, Italy.
Luigi
L
Lay
Department of Pharmaceutical Sciences, University of "Piemonte Orientale, A. Avogadro" , Largo Donegani 2, 28100 Novara, Italy.
Grazia
G
Lombardi
Neisseria meningitidis; glycoconjugates; immune response; vaccines; zwitterionic polysaccharides