title: The Effect of a BSA Conjugate of a Synthetic Hexasaccharide Related to the Fragment of Capsular Polysaccharide of Streptococcus pneumoniae Type 14 on the Activation of Innate and Adaptive Immune Responses.
abstract: We report the effect of a bovine serum albumin (BSA) conjugate of a synthetic hexasaccharide (HS) related to the fragment of the capsular polysaccharide (PS) of Streptococcus pneumoniae type 14 on the stimulation of innate immune system and the subsequent development of a PS-specific antibody response. Glycoconjugate (GC) in the presence (GC + AL) or absence of aluminum hydroxide was administered to mice twice. GC increased the number of TLR2-expressing cells and induced the maturation of dendritic cells (CD11c(+), CD80(+) and, MHCII(+)), which secreted IL-1β, IL-6, and TNFα into the culture medium. The level of IL-1β, IL-10, IFNγ, and TNFα in the blood increased within 24 h after the single GC administration to mice. On day 7, the numbers of splenic CD4(+) and CD8(+) T lymphocytes and B lymphocytes increased. After the second immunization, the levels of CD4(+) and CD8(+) T lymphocytes were lower than in the control, whereas the B cell, NK cell, and MHC class II-expressing cell numbers remained enhanced. However, of the presence of anti-PS, IgG antibodies were not detected. The addition of aluminum hydroxide to GC stimulated the production of GM-CSF, IL-1β, IL-5, IL-6, IL-10, IL-17, IFNγ, and TNFα. Anti-PS IgG1 antibody titers 7 days after the second immunization were high. During that period, normal levels of splenic CD4(+) T lymphocytes were maintained, whereas reduced CD8(+) T lymphocyte numbers and increased levels of B lymphocytes, NK cells, and MHC class II-expressing cell numbers were observed. Anti-PS IgG levels diminished until day 92. A booster immunization with GC + AL stimulated the production of anti-PS IgG memory antibodies, which were determined within 97 days. The elucidation of specific features of the effect of the synthetic HS conjugate on the stimulation of innate, cell-mediated immunity, and antibody response can favor the optimization of GC vaccine design.
authors.affiliation: Department of Immunology, Mechnikov Research Institute for Vaccines and Sera, Russian Academy of Medical Sciences , Moscow , Russia.
authors.forename: Nelli K
authors.initials: NK
authors.lastname: Akhmatova
authors.affiliation: Department of Immunology, Mechnikov Research Institute for Vaccines and Sera, Russian Academy of Medical Sciences , Moscow , Russia.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Kurbatova
authors.affiliation: Department of Immunology, Mechnikov Research Institute for Vaccines and Sera, Russian Academy of Medical Sciences , Moscow , Russia.
authors.forename: Elvin A
authors.initials: EA
authors.lastname: Akhmatov
authors.affiliation: Department of Immunology, Mechnikov Research Institute for Vaccines and Sera, Russian Academy of Medical Sciences , Moscow , Russia.
authors.forename: Nadezhda B
authors.initials: NB
authors.lastname: Egorova
authors.affiliation: Department of Microbiology, Gamaleya Research Institute for Epidemiology and Microbiology, Russian Ministry of Health , Moscow , Russia.
authors.forename: Denis Yu
authors.initials: DY
authors.lastname: Logunov
authors.affiliation: Department of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences , Moscow , Russia.
authors.forename: Marina L
authors.initials: ML
authors.lastname: Gening
authors.affiliation: Department of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences , Moscow , Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Sukhova
authors.affiliation: Department of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences , Moscow , Russia.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Yashunsky
authors.affiliation: Department of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences , Moscow , Russia.
authors.forename: Yury E
authors.initials: YE
authors.lastname: Tsvetkov
authors.affiliation: Department of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences , Moscow , Russia.
authors.forename: Nikolay E
authors.initials: NE
authors.lastname: Nifantiev
keywords: antibody; cell-surface molecule; cytokine; dendritic cell; synthetic hexasaccharide conjugate