دورية أكاديمية
Vaccine Candidate Double Mutant Variants of Enterotoxigenic Escherichia coli Heat-Stable Toxin
| العنوان: | Vaccine Candidate Double Mutant Variants of Enterotoxigenic Escherichia coli Heat-Stable Toxin |
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| المؤلفون: | Ephrem Debebe Zegeye, Yuleima Diaz, Pål Puntervoll |
| المصدر: | Vaccines, Vol 10, Iss 2, p 241 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine |
| مصطلحات موضوعية: | enterotoxigenic Escherichia coli (ETEC), heat-stable enterotoxin (ST), diarrhea, toxoid, vaccine, cross-reaction, Medicine |
| الوصف: | Heat-stable enterotoxin (ST) producing enterotoxigenic Escherichia coli (ETEC) strains are among the top four enteropathogens associated with moderate-to-severe diarrhea in children under five years in low-to-middle income countries, thus making ST a target for an ETEC vaccine. However, ST must be mutated to abolish its enterotoxicity and to prevent a potential immunological cross-reaction due to its structural resemblance to the human peptides uroguanylin and guanylin. To reduce the risk of eliciting cross-reacting antibodies with our lead STh-A14T toxoid, L9 was chosen as an additional mutational target. A double mutant vaccine candidate immunogen, STh-L9A/A14T, was constructed by conjugation to the synthetic virus-like mi3 nanoparticle using the SpyTag/SpyCatcher technology. This immunogen elicited STh neutralizing antibodies in mice, but with less consistency than STh-A14T peptide control immunogens. Moreover, individual sera from mice immunized with both single and double mutant variants displayed varying levels of unwanted cross-reacting antibodies. The lowest levels of cross-reacting antibodies were observed with STh-L9K/A14T control immunogens, suggesting that it is indeed possible to reduce the risk of eliciting cross-reacting antibodies by mutation. However, mutant-specific antibodies were observed for most double mutant immunogens, demonstrating the delicate balancing act between disrupting cross-reacting epitopes, keeping protective ones, and avoiding the formation of neoepitopes. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 10020241 2076-393X |
| العلاقة: | https://www.mdpi.com/2076-393X/10/2/241Test; https://doaj.org/toc/2076-393XTest |
| DOI: | 10.3390/vaccines10020241 |
| الوصول الحر: | https://doaj.org/article/e763f9970df240b0ae2e3d10e46646a2Test |
| رقم الانضمام: | edsdoj.763f9970df240b0ae2e3d10e46646a2 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 10020241 2076393X |
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| DOI: | 10.3390/vaccines10020241 |