Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins
ABSTRACT 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 hos...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-10-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01674-22 |
| _version_ | 1797989976222203904 |
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| author | Natalia Rudenko Anna Karatovskaya Anna Zamyatina Anna Shepelyakovskaya Svetlana Semushina Fedor Brovko Anna Shpirt Vladimir Torgov Natalia Kolotyrkina Alexandr Zinin Anastasiya Kasimova Andrei Perepelov Mikhail Shneider Yuriy Knirel |
| author_facet | Natalia Rudenko Anna Karatovskaya Anna Zamyatina Anna Shepelyakovskaya Svetlana Semushina Fedor Brovko Anna Shpirt Vladimir Torgov Natalia Kolotyrkina Alexandr Zinin Anastasiya Kasimova Andrei Perepelov Mikhail Shneider Yuriy Knirel |
| author_sort | Natalia Rudenko |
| collection | DOAJ |
| description | ABSTRACT 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. IMPORTANCE Immunization by glycoconjugates with A. baumannii type K9 CPS fragments induced a high level of antibodies (predominantly IgG) in sera, which reacted specifically with the CPS of A. baumannii type K9, as well as a long immunological memory. The sera of immunized animals efficiently opsonized A. baumannii type K9. Immunization resulted in the balanced production of pro/anti-inflammatory lymphokines and protective antibodies to ensure the survival of the mice infected with A. baumannii. The level of specific antibodies was sufficient to provide protective immunity against the challenge by A. baumannii, making this approach applicable in the development of vaccine preparations. |
| first_indexed | 2024-04-11T08:29:14Z |
| format | Article |
| id | doaj.art-a0e4a0eac6424a1b8d20edfb3688a1e8 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-11T08:29:14Z |
| publishDate | 2022-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-a0e4a0eac6424a1b8d20edfb3688a1e82022-12-22T04:34:37ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-10-0110510.1128/spectrum.01674-22Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier ProteinsNatalia Rudenko0Anna Karatovskaya1Anna Zamyatina2Anna Shepelyakovskaya3Svetlana Semushina4Fedor Brovko5Anna Shpirt6Vladimir Torgov7Natalia Kolotyrkina8Alexandr Zinin9Anastasiya Kasimova10Andrei Perepelov11Mikhail Shneider12Yuriy Knirel13Laboratory of Immunochemistry, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, RussiaLaboratory of Immunochemistry, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, RussiaLaboratory of Immunochemistry, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, RussiaLaboratory of Immunochemistry, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, RussiaLaboratory of Immunochemistry, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, RussiaLaboratory of Immunochemistry, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, RussiaLaboratory of Carbohydrates and Biocides, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaLaboratory of Carbohydrates and Biocides, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaLaboratory of Carbohydrates and Biocides, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaLaboratory of Carbohydrates and Biocides, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaLaboratory of Carbohydrates and Biocides, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaLaboratory of Carbohydrates and Biocides, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaLaboratory of Molecular Bioengineering, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaLaboratory of Carbohydrates and Biocides, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaABSTRACT 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. IMPORTANCE Immunization by glycoconjugates with A. baumannii type K9 CPS fragments induced a high level of antibodies (predominantly IgG) in sera, which reacted specifically with the CPS of A. baumannii type K9, as well as a long immunological memory. The sera of immunized animals efficiently opsonized A. baumannii type K9. Immunization resulted in the balanced production of pro/anti-inflammatory lymphokines and protective antibodies to ensure the survival of the mice infected with A. baumannii. The level of specific antibodies was sufficient to provide protective immunity against the challenge by A. baumannii, making this approach applicable in the development of vaccine preparations.https://journals.asm.org/doi/10.1128/spectrum.01674-22Acinetobacter baumanniicapsular polysaccharideinterleukinsglycoconjugateopsonisation assay |
| spellingShingle | Natalia Rudenko Anna Karatovskaya Anna Zamyatina Anna Shepelyakovskaya Svetlana Semushina Fedor Brovko Anna Shpirt Vladimir Torgov Natalia Kolotyrkina Alexandr Zinin Anastasiya Kasimova Andrei Perepelov Mikhail Shneider Yuriy Knirel Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins Microbiology Spectrum Acinetobacter baumannii capsular polysaccharide interleukins glycoconjugate opsonisation assay |
| title | Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins |
| title_full | Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins |
| title_fullStr | Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins |
| title_full_unstemmed | Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins |
| title_short | Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins |
| title_sort | immune response to conjugates of fragments of the type k9 capsular polysaccharide of acinetobacter baumannii with carrier proteins |
| topic | Acinetobacter baumannii capsular polysaccharide interleukins glycoconjugate opsonisation assay |
| url | https://journals.asm.org/doi/10.1128/spectrum.01674-22 |
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