Genetically detoxified pertussis toxin displays near identical structure to its wild-type and exhibits robust immunogenicity
| العنوان: | Genetically detoxified pertussis toxin displays near identical structure to its wild-type and exhibits robust immunogenicity |
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| المؤلفون: | Derek J. Wilson, Stephen Li, Salvador F. Ausar, Thomas Bertrand, Jessica Duprez, Roger H. Brookes, Alexey Rak, D. Andrew James, Artur Pedyczak, Shaolong Zhu, Valerie Steier, Anthony Sheung, Michael X Cohen |
| المصدر: | Communications Biology 'Communications Biology ', vol: 3, pages: 427-1-427-12 (2020) Communications Biology, Vol 3, Iss 1, Pp 1-12 (2020) |
| بيانات النشر: | Nature Publishing Group UK, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Protein vaccines, Protein Conformation, Whooping Cough, Protein subunit, Mutant, Medicine (miscellaneous), chemical and pharmacologic phenomena, CHO Cells, Pertussis toxin, Crystallography, X-Ray, complex mixtures, General Biochemistry, Genetics and Molecular Biology, Article, Bordetella pertussis, 03 medical and health sciences, 0302 clinical medicine, Protein structure, Cricetulus, Cricetinae, Animals, Humans, Mass cytometry, lcsh:QH301-705.5, X-ray crystallography, Pertussis Vaccine, Mass spectrometry, Chemistry, Immunogenicity, Wild type, Deuterium Exchange Measurement, Toxoids, Molecular biology, 030104 developmental biology, lcsh:Biology (General), Pertussis Toxin, NAD+ kinase, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery |
| الوصف: | The mutant gdPT R9K/E129G is a genetically detoxified variant of the pertussis toxin (PTx) and represents an attractive candidate for the development of improved pertussis vaccines. The impact of the mutations on the overall protein structure and its immunogenicity has remained elusive. Here we present the crystal structure of gdPT and show that it is nearly identical to that of PTx. Hydrogen-deuterium exchange mass spectrometry revealed dynamic changes in the catalytic domain that directly impacted NAD+ binding which was confirmed by biolayer interferometry. Distal changes in dynamics were also detected in S2-S5 subunit interactions resulting in tighter packing of B-oligomer corresponding to increased thermal stability. Finally, antigen stimulation of human whole blood, analyzed by a previously unreported mass cytometry assay, indicated broader immunogenicity of gdPT compared to pertussis toxoid. These findings establish a direct link between the conserved structure of gdPT and its ability to generate a robust immune response. Ausar et al. show that the crystal structure of gdPT, a mutant pertussis toxin (PTx), is nearly identical to that of PTx. They also find that gdPT exhibits broader immunogenicity than the pertussis toxoid antigen. This study suggests a promising potential of gdPT as an improved acellular pertussis vaccine candidate due to its reduced toxicity and greater immunogenicity. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2399-3642 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f5c21e5acfc882add69441d72d08636bTest http://europepmc.org/articles/PMC7406505Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f5c21e5acfc882add69441d72d08636b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23993642 |
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