TY - JOUR
T1 - 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
AU - Fallarini, Silvia
AU - Buzzi, Benedetta
AU - Giovarruscio, Sara
AU - Polito, Laura
AU - Brogioni, Giulia
AU - Tontini, Marta
AU - Berti, Francesco
AU - Adamo, Roberto
AU - Lay, Luigi
AU - Lombardi, Grazia
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2016/1/8
Y1 - 2016/1/8
N2 - 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 102 μM), whereas only the phosphonodisaccharide was effective (28% of proliferation at 102 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.
AB - 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 102 μM), whereas only the phosphonodisaccharide was effective (28% of proliferation at 102 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.
KW - Neisseria meningitidis
KW - glycoconjugates
KW - immune response
KW - vaccines
KW - zwitterionic polysaccharides
UR - http://www.scopus.com/inward/record.url?scp=84969211533&partnerID=8YFLogxK
U2 - 10.1021/acsinfecdis.5b00071
DO - 10.1021/acsinfecdis.5b00071
M3 - Article
SN - 2373-8227
VL - 1
SP - 487
EP - 496
JO - ACS Infectious Diseases
JF - ACS Infectious Diseases
IS - 10
ER -