Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIX
Abstract Background Mass vaccination of dogs as important rabies reservoir is proposed to most effectively reduce and eliminate rabies also in humans. However, a minimum coverage of 70% needs to be achieved for control of the disease in zoonotic regions. In numerous developing countries, dog vaccina...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | BMC Biotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12896-022-00747-5 |
| _version_ | 1811341641745694720 |
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| author | Khaled Trabelsi Meriem Ben Zakour Ingo Jordan Volker Sandig Samia Rourou Hela Kallel |
| author_facet | Khaled Trabelsi Meriem Ben Zakour Ingo Jordan Volker Sandig Samia Rourou Hela Kallel |
| author_sort | Khaled Trabelsi |
| collection | DOAJ |
| description | Abstract Background Mass vaccination of dogs as important rabies reservoir is proposed to most effectively reduce and eliminate rabies also in humans. However, a minimum coverage of 70% needs to be achieved for control of the disease in zoonotic regions. In numerous developing countries, dog vaccination rate is still dangerously low because of economic constraints and due to a high turnover in dog populations. Improved vaccine production processes may help to alleviate cost and supply limitations. In this work, we studied and optimized the replication and vaccine potency of PV rabies virus strain in the muscovy-duck derived AGE1.CR and AGE1.CR.pIX suspension cell lines. Results The BHK-21-adapted PV rabies virus strain replicated efficiently in the avian cell lines without requirement for prior passaging. CR.pIX was previously shown to augment heat shock responses and supported slightly higher infectious titers compared to the parental CR cell line. Both cell lines allowed replication of rabies virus also in absence of recombinant IGF, the only complex component of the chemically defined medium that was developed for the two cell lines. After scale-up from optimization experiments in shake flask to production in 7-l bioreactors peak virus titers of 2.4 × 108 FFU/ml were obtained. The potency of inactivated rabies virus harvest according to the NIH test was 3.5 IU/ml. Perfusion with the chemically defined medium during the virus replication phase improved the potency of the vaccine twofold, and increased the number of doses 9.6 fold. Conclusion This study demonstrates that a rabies vaccine for animal vaccination can be produced efficiently in the AGE1.CR.pIX suspension cell line in a scalable process in chemically defined medium. |
| first_indexed | 2024-04-13T18:58:14Z |
| format | Article |
| id | doaj.art-5b6b980bd1ed4cbda7438c6555aa128e |
| institution | Directory Open Access Journal |
| issn | 1472-6750 |
| language | English |
| last_indexed | 2024-04-13T18:58:14Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biotechnology |
| spelling | doaj.art-5b6b980bd1ed4cbda7438c6555aa128e2022-12-22T02:34:11ZengBMCBMC Biotechnology1472-67502022-06-0122111010.1186/s12896-022-00747-5Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIXKhaled Trabelsi0Meriem Ben Zakour1Ingo Jordan2Volker Sandig3Samia Rourou4Hela Kallel5Biotechnology Development group, Institut Pasteur de Tunis. Université Tunis El Manar.Biotechnology Development group, Institut Pasteur de Tunis. Université Tunis El Manar.ProBioGen AGProBioGen AGBiotechnology Development group, Institut Pasteur de Tunis. Université Tunis El Manar.Biotechnology Development group, Institut Pasteur de Tunis. Université Tunis El Manar.Abstract Background Mass vaccination of dogs as important rabies reservoir is proposed to most effectively reduce and eliminate rabies also in humans. However, a minimum coverage of 70% needs to be achieved for control of the disease in zoonotic regions. In numerous developing countries, dog vaccination rate is still dangerously low because of economic constraints and due to a high turnover in dog populations. Improved vaccine production processes may help to alleviate cost and supply limitations. In this work, we studied and optimized the replication and vaccine potency of PV rabies virus strain in the muscovy-duck derived AGE1.CR and AGE1.CR.pIX suspension cell lines. Results The BHK-21-adapted PV rabies virus strain replicated efficiently in the avian cell lines without requirement for prior passaging. CR.pIX was previously shown to augment heat shock responses and supported slightly higher infectious titers compared to the parental CR cell line. Both cell lines allowed replication of rabies virus also in absence of recombinant IGF, the only complex component of the chemically defined medium that was developed for the two cell lines. After scale-up from optimization experiments in shake flask to production in 7-l bioreactors peak virus titers of 2.4 × 108 FFU/ml were obtained. The potency of inactivated rabies virus harvest according to the NIH test was 3.5 IU/ml. Perfusion with the chemically defined medium during the virus replication phase improved the potency of the vaccine twofold, and increased the number of doses 9.6 fold. Conclusion This study demonstrates that a rabies vaccine for animal vaccination can be produced efficiently in the AGE1.CR.pIX suspension cell line in a scalable process in chemically defined medium.https://doi.org/10.1186/s12896-022-00747-5Avian cell linesRabies virusProcess optimizationVeterinary rabies vaccine |
| spellingShingle | Khaled Trabelsi Meriem Ben Zakour Ingo Jordan Volker Sandig Samia Rourou Hela Kallel Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIX BMC Biotechnology Avian cell lines Rabies virus Process optimization Veterinary rabies vaccine |
| title | Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIX |
| title_full | Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIX |
| title_fullStr | Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIX |
| title_full_unstemmed | Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIX |
| title_short | Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIX |
| title_sort | development of an efficient veterinary rabies vaccine production process in the avian suspension cell line age1 cr pix |
| topic | Avian cell lines Rabies virus Process optimization Veterinary rabies vaccine |
| url | https://doi.org/10.1186/s12896-022-00747-5 |
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