دورية أكاديمية
Immunoinformatics analysis and evaluation of recombinant chimeric triple antigen toxoid (r-HAB) against Staphylococcus aureus toxaemia in mouse model.
العنوان: | Immunoinformatics analysis and evaluation of recombinant chimeric triple antigen toxoid (r-HAB) against Staphylococcus aureus toxaemia in mouse model. |
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المؤلفون: | Kota RK; Department of Biotechnology, Vignan's Foundation for Science, Technology and Research (Deemed To Be University), Guntur district, Vadlamudi, 522 213, Andhra, Pradesh, India., Kolla HB; Department of Biotechnology, Vignan's Foundation for Science, Technology and Research (Deemed To Be University), Guntur district, Vadlamudi, 522 213, Andhra, Pradesh, India., Reddy PN; Department of Biotechnology, Vignan's Foundation for Science, Technology and Research (Deemed To Be University), Guntur district, Vadlamudi, 522 213, Andhra, Pradesh, India. prakashreddy.369@gmail.com., Kalagatur NK; BU-DRDO Centre for Life Sciences, 641 046, Coimbatore, Tamil Nadu, India., Samudrala SK; Department of Biotechnology, Vignan's Foundation for Science, Technology and Research (Deemed To Be University), Guntur district, Vadlamudi, 522 213, Andhra, Pradesh, India. |
المصدر: | Applied microbiology and biotechnology [Appl Microbiol Biotechnol] 2021 Nov; Vol. 105 (21-22), pp. 8297-8311. Date of Electronic Publication: 2021 Oct 05. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Springer International Country of Publication: Germany NLM ID: 8406612 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0614 (Electronic) Linking ISSN: 01757598 NLM ISO Abbreviation: Appl Microbiol Biotechnol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Berlin ; New York : Springer International, c1984- |
مواضيع طبية MeSH: | Bacterial Toxins*/genetics , Toxemia*, Animals ; Antibodies, Bacterial ; Enterotoxins ; Escherichia coli/genetics ; Mice ; Mice, Inbred BALB C ; Staphylococcus aureus ; Toxoids |
مستخلص: | Staphylococcus aureus is a serious pathogen unleashing its virulence through several classes of exotoxins such as hemolysins and enterotoxins. In this study, we designed a novel multi-antigen subunit vaccine which can induce innate, humoral and cellular immune responses. Alpha hemolysin, enterotoxins A and B were selected as protective antigens for combining into a triple antigen chimeric protein (HAB). Immunoinformatics analysis predicted HAB protein as a suitable vaccine candidate for inducing both humoral and cellular immune responses. Tertiary structure of the HAB protein was predicted and validated through computational approaches. Docking studies were performed between the HAB protein and mice TLR2 receptor. Furthermore, we constructed and generated recombinant HAB (r-HAB) protein in E. coli and studied its toxicity, immunogenicity and protective efficacy in a mouse model. Triple antigen chimeric protein (r-HAB) was found to be highly immunogenic in mouse as the anti-r-HAB hyperimmune serum was strongly reactive to all three native exotoxins on Western blot. In vitro toxin neutralization assay using anti-r-HAB antibodies demonstrated > 75% neutralization of toxins on RAW 264.7 cell line. Active immunization with r-HAB toxoid gave ~ 83% protection against 2 × lethal dosage of secreted exotoxins. The protection was mediated by induction of strong antibody responses that neutralized the toxins. Passive immunization with anti-r-HAB antibodies gave ~ 50% protection from lethal challenge. In conclusion, in vitro and in vivo testing of r-HAB found the molecule to be nontoxic, highly immunogenic and induced excellent protection towards native toxins in actively immunized and partial protection to passively immunized mice groups. KEY POINTS: • HAB protein was computationally designed to induce humoral and cellular responses. • r-HAB protein was found to be nontoxic, immunogenic and protective in mouse model. • r-HAB conferred protection against lethal challenge in active and passive immunization. (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) |
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معلومات مُعتمدة: | DST/INSPIRE/04/2017/000565 Department of Science and Technology, Ministry of Science and Technology |
فهرسة مساهمة: | Keywords: Alpha hemolysin; Enterotoxin A; Enterotoxin B; Immunoinformatics; Lethal challenge; Staphylococcus aureus; Subunit vaccine |
المشرفين على المادة: | 0 (Antibodies, Bacterial) 0 (Bacterial Toxins) 0 (Enterotoxins) 0 (Toxoids) |
تواريخ الأحداث: | Date Created: 20211005 Date Completed: 20211102 Latest Revision: 20211102 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC8490849 |
DOI: | 10.1007/s00253-021-11609-z |
PMID: | 34609523 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1432-0614 |
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DOI: | 10.1007/s00253-021-11609-z |