Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins

Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins Full article

Journal

Microbiology spectrum
ISSN: 2165-0497

Output data

Year: 2022, Volume: 10, Number: 5, Article number : e01674-22, Pages count : DOI: 10.1128/spectrum.01674-22

Authors

Rudenko Natalia ¹ , Karatovskaya Anna ¹ , Zamyatina Anna ¹ , Shepelyakovskaya Anna ¹ , Semushina Svetlana ¹ , Brovko Fedor ¹ , Shpirt Anna ² , Torgov Vladimir ² , Kolotyrkina Natalia ² , Zinin Alexandr ² , Kasimova Anastasiya ² , Perepelov Andrei ² , Shneider Mikhail ³ , Knirel Yuriy ²

Affiliations

1	Laboratory of Immunochemistry, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, Russia
2	Laboratory of Carbohydrates and Biocides, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
3	Laboratory of Molecular Bioengineering, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia

The clonal bacterial species Acinetobacter baumannii is an emerging multidrug-resistant pathogen which causes high-lethality infections. Cells of A. baumannii are surrounded by the type-specific capsular polysaccharide (CPS), which provides resistance to the protective mechanisms of the host and is considered a target for immunization. The conjugates of three inert carrier proteins and A. baumannii type K9 CPS fragments, which contained various numbers of oligosaccharide repeats (K-units), were synthesized by periodate oxidation and squaric acid chemistry. The conjugates were applied to immunize mice, and chemical synthesis by squaric acid was shown to significantly improve the immunogenic properties of glycoconjugate. In BALB/c mice, IgG antibodies were predominant among type K9 CPS reactive antibodies, and their total content was several times higher than that of IgM. Immune sera were characterized by their opsonization ability during practically the entire lives of the experimental mice. The sera were cross-reactive, but the highest specificity was observed against the antigen (type K9 CPS) used for immunization. The immunization of BALB/c and ICR-1 mice with a glycoconjugate without adjuvants led to varying degrees of stimulation of IL-10, IL-17A, and TNF-α production, but not IL-4 production in the ICR-1 mice. This is in contrast to the BALB/c mice, in which γ-IFN production was also activated. The protective effectiveness of the glycoconjugates obtained by squaric acid chemistry was demonstrated by experiments that involved challenging immunized and nonimmunized animals with a lethal dose of A. baumannii K9.

Rudenko N. , Karatovskaya A. , Zamyatina A. , Shepelyakovskaya A. , Semushina S. , Brovko F. , Shpirt A. , Torgov V. , Kolotyrkina N. , Zinin A. , Kasimova A. , Perepelov A. , Shneider M. , Knirel Y.
Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins
Microbiology spectrum. 2022. V.10. N5. e01674-22 . DOI: 10.1128/spectrum.01674-22 WOS Scopus OpenAlex

Web of science:	WOS:000842388300003
Scopus:	2-s2.0-85140856031
OpenAlex:	W4292210464

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OpenAlex	8
Scopus	6
Web of science	6