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…

Nelli K. Akhmatova, Ekaterina A. Kurbatova, Elvin A. Akhmatov, Nadezhda B. Egorova, Denis Yu. Logunov, Marina L. Gening, Elena V. Sukhova, Dmitry V. Yashunsky, Yury E. Tsvetkov, Nikolay E. Nifantiev

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.