Designing Stable <i>Bacillus anthracis</i> Antigens with a View to Recombinant Anthrax Vaccine Development
Anthrax is a disease caused by <i>Bacillus anthracis</i> that affects mammals, including humans. Recombinant <i>B. anthracis</i> protective antigen (rPA) is the most common basis for modern anthrax vaccine candidates. However, this protein is characterised by low stability du...
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MDPI AG
2022-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/4/806 |
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| author | Ekaterina M. Ryabchevskaya Dmitriy L. Granovskiy Ekaterina A. Evtushenko Peter A. Ivanov Olga A. Kondakova Nikolai A. Nikitin Olga V. Karpova |
| author_facet | Ekaterina M. Ryabchevskaya Dmitriy L. Granovskiy Ekaterina A. Evtushenko Peter A. Ivanov Olga A. Kondakova Nikolai A. Nikitin Olga V. Karpova |
| author_sort | Ekaterina M. Ryabchevskaya |
| collection | DOAJ |
| description | Anthrax is a disease caused by <i>Bacillus anthracis</i> that affects mammals, including humans. Recombinant <i>B. anthracis</i> protective antigen (rPA) is the most common basis for modern anthrax vaccine candidates. However, this protein is characterised by low stability due to proteolysis and deamidation. Here, for the first time, two modification variants leading to full-size rPA stabilisation have been implemented simultaneously, through deamidation-prone asparagine residues substitution and by inactivation of proteolysis sites. Obtained modified rPA (rPA83m) has been demonstrated to be stable in various temperature conditions. Additionally, rPA1+2 containing PA domains I and II and rPA3+4 containing domains III and IV, including the same modifications, have been shown to be stable as well. These antigens can serve as the basis for a vaccine, since the protective properties of PA can be attributed to individual PA domains. The stability of each of three modified anthrax antigens has been considerably improved in compositions with tobacco mosaic virus-based spherical particles (SPs). rPA1+2/rPA3+4/rPA83m in compositions with SPs have maintained their antigenic specificity even after 40 days of incubation at +37 °C. Considering previously proven adjuvant properties and safety of SPs, their compositions with rPA83m/rPA1+2/rPA3+4 in any combinations might be suitable as a basis for new-generation anthrax vaccines. |
| first_indexed | 2024-03-09T13:09:11Z |
| format | Article |
| id | doaj.art-f7fdbfeb8ab04f979e388f3ec9dc0171 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T13:09:11Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-f7fdbfeb8ab04f979e388f3ec9dc01712023-11-30T21:44:25ZengMDPI AGPharmaceutics1999-49232022-04-0114480610.3390/pharmaceutics14040806Designing Stable <i>Bacillus anthracis</i> Antigens with a View to Recombinant Anthrax Vaccine DevelopmentEkaterina M. Ryabchevskaya0Dmitriy L. Granovskiy1Ekaterina A. Evtushenko2Peter A. Ivanov3Olga A. Kondakova4Nikolai A. Nikitin5Olga V. Karpova6Department of Virology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaDepartment of Virology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaDepartment of Virology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaDepartment of Virology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaDepartment of Virology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaDepartment of Virology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaDepartment of Virology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaAnthrax is a disease caused by <i>Bacillus anthracis</i> that affects mammals, including humans. Recombinant <i>B. anthracis</i> protective antigen (rPA) is the most common basis for modern anthrax vaccine candidates. However, this protein is characterised by low stability due to proteolysis and deamidation. Here, for the first time, two modification variants leading to full-size rPA stabilisation have been implemented simultaneously, through deamidation-prone asparagine residues substitution and by inactivation of proteolysis sites. Obtained modified rPA (rPA83m) has been demonstrated to be stable in various temperature conditions. Additionally, rPA1+2 containing PA domains I and II and rPA3+4 containing domains III and IV, including the same modifications, have been shown to be stable as well. These antigens can serve as the basis for a vaccine, since the protective properties of PA can be attributed to individual PA domains. The stability of each of three modified anthrax antigens has been considerably improved in compositions with tobacco mosaic virus-based spherical particles (SPs). rPA1+2/rPA3+4/rPA83m in compositions with SPs have maintained their antigenic specificity even after 40 days of incubation at +37 °C. Considering previously proven adjuvant properties and safety of SPs, their compositions with rPA83m/rPA1+2/rPA3+4 in any combinations might be suitable as a basis for new-generation anthrax vaccines.https://www.mdpi.com/1999-4923/14/4/806<i>Bacillus anthracis</i>recombinant protective antigenvaccinesstabilisationstructurally modified plant virusestobacco mosaic virus |
| spellingShingle | Ekaterina M. Ryabchevskaya Dmitriy L. Granovskiy Ekaterina A. Evtushenko Peter A. Ivanov Olga A. Kondakova Nikolai A. Nikitin Olga V. Karpova Designing Stable <i>Bacillus anthracis</i> Antigens with a View to Recombinant Anthrax Vaccine Development Pharmaceutics <i>Bacillus anthracis</i> recombinant protective antigen vaccines stabilisation structurally modified plant viruses tobacco mosaic virus |
| title | Designing Stable <i>Bacillus anthracis</i> Antigens with a View to Recombinant Anthrax Vaccine Development |
| title_full | Designing Stable <i>Bacillus anthracis</i> Antigens with a View to Recombinant Anthrax Vaccine Development |
| title_fullStr | Designing Stable <i>Bacillus anthracis</i> Antigens with a View to Recombinant Anthrax Vaccine Development |
| title_full_unstemmed | Designing Stable <i>Bacillus anthracis</i> Antigens with a View to Recombinant Anthrax Vaccine Development |
| title_short | Designing Stable <i>Bacillus anthracis</i> Antigens with a View to Recombinant Anthrax Vaccine Development |
| title_sort | designing stable i bacillus anthracis i antigens with a view to recombinant anthrax vaccine development |
| topic | <i>Bacillus anthracis</i> recombinant protective antigen vaccines stabilisation structurally modified plant viruses tobacco mosaic virus |
| url | https://www.mdpi.com/1999-4923/14/4/806 |
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