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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1388721
This article is part of the Research Topic Systems immunology to advance vaccine development View all 14 articles

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

Provisionally accepted
Ekaterina A. Kurbatova Ekaterina A. Kurbatova 1*Nelli Akhmatova Nelli Akhmatova 2Anton E. Zaytsev Anton E. Zaytsev 2Elina Akhmatova Elina Akhmatova 2Natalya E. Yastrebova Natalya E. Yastrebova 2Elena V. Sukhova Elena V. Sukhova 3Dmitriy V. Yashunsky Dmitriy V. Yashunsky 3Yury Tsvetkov Yury Tsvetkov 3Nikolay E. Nifantiev Nikolay E. Nifantiev 3*
  • 1 Other
  • 2 I.I. Mechnikov Research Institute of Vaccines and Sera (RAS), Moscow, Moscow Oblast, Russia
  • 3 N.D. Zelinsky Institute of Organic Chemistry (RAS), Moscow, Moscow Oblast, Russia

The final, formatted version of the article will be published soon.

    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.

    Keywords: Streptococcus pneumoniae serotype 3, synthetic disaccharide, cytokine, γδ T cells, B1 Cells, Interleukin 17A, antibody, mice immunoprotection

    Received: 20 Feb 2024; Accepted: 06 May 2024.

    Copyright: © 2024 Kurbatova, Akhmatova, Zaytsev, Akhmatova, Yastrebova, Sukhova, Yashunsky, Tsvetkov and Nifantiev. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Nikolay E. Nifantiev, N.D. Zelinsky Institute of Organic Chemistry (RAS), Moscow, Moscow Oblast, Russia

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