EFFECT OF ALUMINIUM HYDROXIDE ON INNATE IMMUNITY AND IMMUNOGENICITY OF BACTERIAL AND SYNTHETIC ANTIGENS OF STREPTOCOCCUS PNEUMONIAE


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Abstract

Aim. Study the effect of aluminium hydroxide on molecular-cell mechanisms of innate immunity activation and its adjuvant effect on immunogenicity of natural bacterial and synthetic pneumococci antigens. Materials and methods. Surface markers of dendritic cells (DC), mononuclear leukocytes (ML) and cytokine levels were determined by flow cytometry; IgG titers - by EIA. Protective activity was evaluated in experiments with active protection of mice from infection with virulent pneumococci strains. Results. Aluminium hydroxide increased the ML content of mice spleen expressing TLR2 and TLR4. Its addition into the culture of immature DC induced the appearance of a population of cells with mature DC markers - CD83, CD80, CD86, however, the level of undifferentiated cells (CD34) and cells with adhesion molecules (CD11c, CD38) did not change. DC produced IL-ф, IL-5, IL-10, IFNy into the cultivation medium. An increase of cytokine production took place 2 hours after the administration into mice and was retained for the observation period (24 hours). Th1 (IFNy, TNFa) and Th2 (IL-5, IL-10, GM-CSF) cytokine production gave evidence on immune response polarization by Th1/Th2 type. After 2 administrations of aluminium hydroxide into mice the number of ML with CD19+, CD5+, NK1.1+, CD25+, MHCII+ markers increased during decrease of CD3+, CD4+ and CD8+ T-lymphocytes. Adaptive immunity activation was characterized by high IgG titers to pneumococci capsule polysaccharide and protection of 90 - 100% of the mice against infection with lethal doses of S. pneumoniae strains, was detected during 2-fold immunization of mice with conjugates of synthetic pneumococci oligosaccharides with BSA, sorbed onto aluminium hydroxide, whereas natural bacterial antigens provided 90 - 100% survival of animals during immunization without the adjuvant. Conclusion. Data are provided on the effect of aluminium hydroxide on key effectors of innate immunity: DC, ML, TLRs and cytokine production. A reasonable administration of this adjuvant was shown to be in association with conjugates of pneumococci synthetic oligosaccharides with a carrier protein.

About the authors

E. A Kurbatova

Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia

E. A Akhmatov

Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia

N. K Akhmatova

Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia

D. S Vorobiev

Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia

N. B Egorova

Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia

A. P Baturo

Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia

E. E Romanenko

Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia

Yu. E Tsvetkov

Zelinsky Institute of Organic Chemistry, Moscow, Russia

E. V Sukhova

Zelinsky Institute of Organic Chemistry, Moscow, Russia

D. V Yashunsky

Orekhovich Research Institute of Biomedical Chemistry, Moscow, Russia

N. E Nifantiev

Zelinsky Institute of Organic Chemistry, Moscow, Russia

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Copyright (c) 2014 Kurbatova E.A., Akhmatov E.A., Akhmatova N.K., Vorobiev D.S., Egorova N.B., Baturo A.P., Romanenko E.E., Tsvetkov Y.E., Sukhova E.V., Yashunsky D.V., Nifantiev N.E.

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