Production of a chimeric porcine reproductive and respiratory syndrome virus (PRRSV)-2 vaccine using a lab-scale packed-bed bioreactor CelCradle

Abstract Background We developed a MARC-145 cell culture and porcine reproductive and respiratory syndrome (PRRS) vaccine production using a novel CelCradle bioreactor. CelCradle is a packed-bed bioreactor capable of both batch and perfusion culture, and the operating parameters are easy to optimize...

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Main Authors: Hwi-Yeon Choi, Jong-Chul Choi, Yeong-Lim Kang, So-Hyeun Ahn, Sang-Won Lee, Seung-Yong Park, Chang-Seon Song, In-Soo Choi, Joong-Bok Lee
Format: Article
Language:English
Published: BMC 2023-08-01
Series:BMC Veterinary Research
Subjects:
Online Access:https://doi.org/10.1186/s12917-023-03659-4
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author Hwi-Yeon Choi
Jong-Chul Choi
Yeong-Lim Kang
So-Hyeun Ahn
Sang-Won Lee
Seung-Yong Park
Chang-Seon Song
In-Soo Choi
Joong-Bok Lee
author_facet Hwi-Yeon Choi
Jong-Chul Choi
Yeong-Lim Kang
So-Hyeun Ahn
Sang-Won Lee
Seung-Yong Park
Chang-Seon Song
In-Soo Choi
Joong-Bok Lee
author_sort Hwi-Yeon Choi
collection DOAJ
description Abstract Background We developed a MARC-145 cell culture and porcine reproductive and respiratory syndrome (PRRS) vaccine production using a novel CelCradle bioreactor. CelCradle is a packed-bed bioreactor capable of both batch and perfusion culture, and the operating parameters are easy to optimize. Results In this study, CelCradle reached a maximum cell density of 8.94 × 105 cells/mL at 5 days post-seeding when seeded at 8.60 × 104 cells/mL (doubling time = 35.52 h). Inoculation of PRRS vaccine candidate, K418DM1.1, was performed at a multiplicity of infection (MOI) of 0.01 at 5 days post-seeding, which resulted in a high viral titer of 2.04 × 108 TCID50/mL and total viral load of 1.02 × 1011 TCID50/500 mL at 2 days post-infection (dpi). The multilayer cultivation system, BioFactory culture, yielded a higher doubling time (37.14 h) and lower viral titer (i.e., 8.15 × 107 TCID50/mL) compared to the CelCradle culture. Thus, the culture medium productivity of the CelCradle culture was 2-fold higher than that of the BioFactory culture. In the animal experiment, the CelCradle-produced vaccine induced high levels of neutralizing antibodies and effectively protected pigs against homologous challenge, as shown by the significantly lower levels of viremia at 1- and 7-days post-challenge (dpc) compared to the non-vaccinated pigs. Conclusions Overall, this study demonstrates that the CelCradle system is an economical platform for PRRS vaccine production.
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spelling doaj.art-b9720a16908646f2a4ff21730b4792692023-11-26T13:37:59ZengBMCBMC Veterinary Research1746-61482023-08-0119111210.1186/s12917-023-03659-4Production of a chimeric porcine reproductive and respiratory syndrome virus (PRRSV)-2 vaccine using a lab-scale packed-bed bioreactor CelCradleHwi-Yeon Choi0Jong-Chul Choi1Yeong-Lim Kang2So-Hyeun Ahn3Sang-Won Lee4Seung-Yong Park5Chang-Seon Song6In-Soo Choi7Joong-Bok Lee8Laboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk UniversityLaboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk UniversityLaboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk UniversityLaboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk UniversityLaboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk UniversityLaboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk UniversityLaboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk UniversityLaboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk UniversityLaboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk UniversityAbstract Background We developed a MARC-145 cell culture and porcine reproductive and respiratory syndrome (PRRS) vaccine production using a novel CelCradle bioreactor. CelCradle is a packed-bed bioreactor capable of both batch and perfusion culture, and the operating parameters are easy to optimize. Results In this study, CelCradle reached a maximum cell density of 8.94 × 105 cells/mL at 5 days post-seeding when seeded at 8.60 × 104 cells/mL (doubling time = 35.52 h). Inoculation of PRRS vaccine candidate, K418DM1.1, was performed at a multiplicity of infection (MOI) of 0.01 at 5 days post-seeding, which resulted in a high viral titer of 2.04 × 108 TCID50/mL and total viral load of 1.02 × 1011 TCID50/500 mL at 2 days post-infection (dpi). The multilayer cultivation system, BioFactory culture, yielded a higher doubling time (37.14 h) and lower viral titer (i.e., 8.15 × 107 TCID50/mL) compared to the CelCradle culture. Thus, the culture medium productivity of the CelCradle culture was 2-fold higher than that of the BioFactory culture. In the animal experiment, the CelCradle-produced vaccine induced high levels of neutralizing antibodies and effectively protected pigs against homologous challenge, as shown by the significantly lower levels of viremia at 1- and 7-days post-challenge (dpc) compared to the non-vaccinated pigs. Conclusions Overall, this study demonstrates that the CelCradle system is an economical platform for PRRS vaccine production.https://doi.org/10.1186/s12917-023-03659-4Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)Vaccine productionCelCradlePacked BedBioreactorVaccine efficacy
spellingShingle Hwi-Yeon Choi
Jong-Chul Choi
Yeong-Lim Kang
So-Hyeun Ahn
Sang-Won Lee
Seung-Yong Park
Chang-Seon Song
In-Soo Choi
Joong-Bok Lee
Production of a chimeric porcine reproductive and respiratory syndrome virus (PRRSV)-2 vaccine using a lab-scale packed-bed bioreactor CelCradle
BMC Veterinary Research
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)
Vaccine production
CelCradle
Packed Bed
Bioreactor
Vaccine efficacy
title Production of a chimeric porcine reproductive and respiratory syndrome virus (PRRSV)-2 vaccine using a lab-scale packed-bed bioreactor CelCradle
title_full Production of a chimeric porcine reproductive and respiratory syndrome virus (PRRSV)-2 vaccine using a lab-scale packed-bed bioreactor CelCradle
title_fullStr Production of a chimeric porcine reproductive and respiratory syndrome virus (PRRSV)-2 vaccine using a lab-scale packed-bed bioreactor CelCradle
title_full_unstemmed Production of a chimeric porcine reproductive and respiratory syndrome virus (PRRSV)-2 vaccine using a lab-scale packed-bed bioreactor CelCradle
title_short Production of a chimeric porcine reproductive and respiratory syndrome virus (PRRSV)-2 vaccine using a lab-scale packed-bed bioreactor CelCradle
title_sort production of a chimeric porcine reproductive and respiratory syndrome virus prrsv 2 vaccine using a lab scale packed bed bioreactor celcradle
topic Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)
Vaccine production
CelCradle
Packed Bed
Bioreactor
Vaccine efficacy
url https://doi.org/10.1186/s12917-023-03659-4
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