Protective vaccination against murine visceral leishmaniasis using aldehyde-containingQuillaja saponariasapogenins

• Published in: Vaccine Vol. 22; no. 19; p. 2470
• Main Authors: Palatnik de Sousa, CB, Santos, WR, Casas, CP, Paraguai de Souza, E, Tinoco, LW, da Silva, BP, Palatnik, M, Parente, JP
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Limited 23-06-2004
• Subjects: Aqueous solutions; Chemical treatment; Clinical trials; Dogs; Drug dosages; Immune response; Immune system; Immunotherapy; Ligands; Rodents; Tropical diseases; Vaccines; Vector-borne diseases
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2004.01.072

The presence of aldehyde groups at C-23 and C-24 of the triterpen aglycon moiety was disclosed in 1HNMR spectra of both the Riedel de Haen saponin (R) (δ9.336) andQuillaja saponariaQuilA saponin (δ9.348). The sign of the C-28 acylated linked moiety (δ176) was present in both saponins, while theδ171 at C-28 (carboxy group) corresponding to the deacylated saponin, was only detected in the QuilA preparation, indicating 50% of hydrolysis of the ester moiety, probably due to the storage in aqueous solution. The normoterpen moiety was present in both saponins (signals atδ14-18).The chemical removal of saponin glicidic moieties gave rise to their sapogenin fractions. Their 1HNMR spectra showed the presence of two signals (δ9.226 and 9.236) for sapogenin R and two signals (δ9.338 and 9.352) for the QuilA sapogenin. The intensity of the signals suggested two conformational isomers of sapogenin R in the ratio 53% of equatorial aldehyde group to 47% of axial aldehyde group, and two conformational isomers of QuilA sapogenin in the ratio 76% of equatorial aldehyde group to 24% of axial aldehyde group. The chemical treatment abolished the saponin slight in vivo toxicity, reduced their hemolytic potential, did not affect their aldehyde contents, but gave rise to an enriched axial aldehyde-containing sapogenin R with enhanced potential on antibody humoral response (anti-IgM, IgG, IgG1, IgG2a, IgG2b and IgG3) and to an enriched equatorial aldehyde-containing QuilA-sapogenin that induced a mainly cellular specific immune response (increased intradermal response to leishmanial antigen and IFNγ sera levels) and effective protection against murine infection byL. donovani(77% reduction in liver parasitic load). Our results suggest that the Riedel de Haen saponin is probably aQuillaja saponariasaponin.