Synthetic BSA-conjugated disaccharide related to the Streptococcus pneumoniae serotype 3 capsular polysaccharide increases IL-17A Levels, γδ T cells, and B1 cells in mice.

Autor:	Akhmatova NK; Laboratory of Therapeutic Vaccines, Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia., Kurbatova EA; Laboratory of Therapeutic Vaccines, Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia., Zaytsev AE; Laboratory of Therapeutic Vaccines, Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia., Akhmatova EA; Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Science, Moscow, Russia., Yastrebova NE; Laboratory of Therapeutic Vaccines, Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia., Sukhova EV; Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Science, Moscow, Russia., Yashunsky DV; Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Science, Moscow, Russia., Tsvetkov YE; Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Science, Moscow, Russia., Nifantiev NE; Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Science, Moscow, Russia.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 May 22; Vol. 15, pp. 1388721. Date of Electronic Publication: 2024 May 22 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1388721
Abstrakt:	The disaccharide (β-D-glucopyranosyluronic acid)-(1→4)-β-D-glucopyranoside represents a repeating unit of the capsular polysaccharide of Streptococcus pneumoniae serotype 3. A conjugate of the disaccharide with BSA (di-BSA conjugate) adjuvanted with aluminum hydroxide induced - in contrast to the non-adjuvanted conjugate - IgG1 antibody production and protected mice against S. pneumoniae serotype 3 infection after intraperitoneal prime-boost immunization. Adjuvanted and non-adjuvanted conjugates induced production of Th1 (IFNγ, TNFα); Th2 (IL-5, IL-13); Th17 (IL-17A), Th1/Th17 (IL-22), and Th2/Th17 cytokines (IL-21) after immunization. The concentration of cytokines in mice sera was higher in response to the adjuvanted conjugate, with the highest level of IL-17A production after the prime and boost immunizations. In contrast, the non-adjuvanted conjugate elicited only weak production of IL-17A, which gradually decreased after the second immunization. After boost immunization of mice with the adjuvanted di-BSA conjugate, there was a significant increase in the number of CD45+/CD19+ B cells, TCR+ γδ T cell, CD5+ В1 cells, and activated cells with MHC II+ expression in the spleens of the mice. IL-17A, TCR+ γδ T cells, and CD5+ В1 cells play a crucial role in preventing pneumococcal infection, but can also contribute to autoimmune diseases. Immunization with the adjuvanted and non-adjuvanted di-BSA conjugate did not elicit autoantibodies against double-stranded DNA targeting cell nuclei in mice. Thus, the molecular and cellular markers associated with antibody production and protective activity in response to immunization with the di-BSA conjugate adjuvanted with aluminum hydroxide are IL-17A, TCR+ γδ T cells, and CD5+ В1 cells against the background of increasing MHC II+ expression. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Akhmatova, Kurbatova, Zaytsev, Akhmatova, Yastrebova, Sukhova, Yashunsky, Tsvetkov and Nifantiev.)
Databáze:	MEDLINE
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