Zika virus-like particles (VLPs): Stable cell lines and continuous perfusion processes as a new potential vaccine manufacturing platform
Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Alvim, Renata G.F. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2019transfer abstract |
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| Schlagwörter: |
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| Umfang: |
8 |
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| Übergeordnetes Werk: |
Enthalten in: Quantifying contributions of leaf area and longevity to leaf area duration under increased planting density and nitrogen input regimens during maize yield improvement - Li, Yaoyao ELSEVIER, 2022, Amsterdam |
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| Übergeordnetes Werk: |
volume:37 ; year:2019 ; number:47 ; day:8 ; month:11 ; pages:6970-6977 ; extent:8 |
| Links: |
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| DOI / URN: |
10.1016/j.vaccine.2019.05.064 |
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| Katalog-ID: |
ELV048339709 |
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| 520 | |a Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. | ||
| 520 | |a Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. | ||
| 650 | 7 | |a HEK293 cells |2 Elsevier | |
| 650 | 7 | |a Perfusion |2 Elsevier | |
| 650 | 7 | |a Upstream process |2 Elsevier | |
| 650 | 7 | |a Stable expression |2 Elsevier | |
| 650 | 7 | |a Zika virus |2 Elsevier | |
| 650 | 7 | |a Virus-like particles (VLPs) |2 Elsevier | |
| 700 | 1 | |a Itabaiana, Ivaldo |4 oth | |
| 700 | 1 | |a Castilho, Leda R. |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier |a Li, Yaoyao ELSEVIER |t Quantifying contributions of leaf area and longevity to leaf area duration under increased planting density and nitrogen input regimens during maize yield improvement |d 2022 |g Amsterdam |w (DE-627)ELV007884451 |
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10.1016/j.vaccine.2019.05.064 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000870.pica (DE-627)ELV048339709 (ELSEVIER)S0264-410X(19)30701-7 DE-627 ger DE-627 rakwb eng 630 640 VZ 48.00 bkl Alvim, Renata G.F. verfasserin aut Zika virus-like particles (VLPs): Stable cell lines and continuous perfusion processes as a new potential vaccine manufacturing platform 2019transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. HEK293 cells Elsevier Perfusion Elsevier Upstream process Elsevier Stable expression Elsevier Zika virus Elsevier Virus-like particles (VLPs) Elsevier Itabaiana, Ivaldo oth Castilho, Leda R. oth Enthalten in Elsevier Li, Yaoyao ELSEVIER Quantifying contributions of leaf area and longevity to leaf area duration under increased planting density and nitrogen input regimens during maize yield improvement 2022 Amsterdam (DE-627)ELV007884451 volume:37 year:2019 number:47 day:8 month:11 pages:6970-6977 extent:8 https://doi.org/10.1016/j.vaccine.2019.05.064 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 37 2019 47 8 1108 6970-6977 8 |
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10.1016/j.vaccine.2019.05.064 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000870.pica (DE-627)ELV048339709 (ELSEVIER)S0264-410X(19)30701-7 DE-627 ger DE-627 rakwb eng 630 640 VZ 48.00 bkl Alvim, Renata G.F. verfasserin aut Zika virus-like particles (VLPs): Stable cell lines and continuous perfusion processes as a new potential vaccine manufacturing platform 2019transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. HEK293 cells Elsevier Perfusion Elsevier Upstream process Elsevier Stable expression Elsevier Zika virus Elsevier Virus-like particles (VLPs) Elsevier Itabaiana, Ivaldo oth Castilho, Leda R. oth Enthalten in Elsevier Li, Yaoyao ELSEVIER Quantifying contributions of leaf area and longevity to leaf area duration under increased planting density and nitrogen input regimens during maize yield improvement 2022 Amsterdam (DE-627)ELV007884451 volume:37 year:2019 number:47 day:8 month:11 pages:6970-6977 extent:8 https://doi.org/10.1016/j.vaccine.2019.05.064 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 37 2019 47 8 1108 6970-6977 8 |
| allfields_unstemmed |
10.1016/j.vaccine.2019.05.064 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000870.pica (DE-627)ELV048339709 (ELSEVIER)S0264-410X(19)30701-7 DE-627 ger DE-627 rakwb eng 630 640 VZ 48.00 bkl Alvim, Renata G.F. verfasserin aut Zika virus-like particles (VLPs): Stable cell lines and continuous perfusion processes as a new potential vaccine manufacturing platform 2019transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. HEK293 cells Elsevier Perfusion Elsevier Upstream process Elsevier Stable expression Elsevier Zika virus Elsevier Virus-like particles (VLPs) Elsevier Itabaiana, Ivaldo oth Castilho, Leda R. oth Enthalten in Elsevier Li, Yaoyao ELSEVIER Quantifying contributions of leaf area and longevity to leaf area duration under increased planting density and nitrogen input regimens during maize yield improvement 2022 Amsterdam (DE-627)ELV007884451 volume:37 year:2019 number:47 day:8 month:11 pages:6970-6977 extent:8 https://doi.org/10.1016/j.vaccine.2019.05.064 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 37 2019 47 8 1108 6970-6977 8 |
| allfieldsGer |
10.1016/j.vaccine.2019.05.064 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000870.pica (DE-627)ELV048339709 (ELSEVIER)S0264-410X(19)30701-7 DE-627 ger DE-627 rakwb eng 630 640 VZ 48.00 bkl Alvim, Renata G.F. verfasserin aut Zika virus-like particles (VLPs): Stable cell lines and continuous perfusion processes as a new potential vaccine manufacturing platform 2019transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. HEK293 cells Elsevier Perfusion Elsevier Upstream process Elsevier Stable expression Elsevier Zika virus Elsevier Virus-like particles (VLPs) Elsevier Itabaiana, Ivaldo oth Castilho, Leda R. oth Enthalten in Elsevier Li, Yaoyao ELSEVIER Quantifying contributions of leaf area and longevity to leaf area duration under increased planting density and nitrogen input regimens during maize yield improvement 2022 Amsterdam (DE-627)ELV007884451 volume:37 year:2019 number:47 day:8 month:11 pages:6970-6977 extent:8 https://doi.org/10.1016/j.vaccine.2019.05.064 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 37 2019 47 8 1108 6970-6977 8 |
| allfieldsSound |
10.1016/j.vaccine.2019.05.064 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000870.pica (DE-627)ELV048339709 (ELSEVIER)S0264-410X(19)30701-7 DE-627 ger DE-627 rakwb eng 630 640 VZ 48.00 bkl Alvim, Renata G.F. verfasserin aut Zika virus-like particles (VLPs): Stable cell lines and continuous perfusion processes as a new potential vaccine manufacturing platform 2019transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. HEK293 cells Elsevier Perfusion Elsevier Upstream process Elsevier Stable expression Elsevier Zika virus Elsevier Virus-like particles (VLPs) Elsevier Itabaiana, Ivaldo oth Castilho, Leda R. oth Enthalten in Elsevier Li, Yaoyao ELSEVIER Quantifying contributions of leaf area and longevity to leaf area duration under increased planting density and nitrogen input regimens during maize yield improvement 2022 Amsterdam (DE-627)ELV007884451 volume:37 year:2019 number:47 day:8 month:11 pages:6970-6977 extent:8 https://doi.org/10.1016/j.vaccine.2019.05.064 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 37 2019 47 8 1108 6970-6977 8 |
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Zika virus-like particles (VLPs): Stable cell lines and continuous perfusion processes as a new potential vaccine manufacturing platform |
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Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. |
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Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. |
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Zika virus (ZIKV) was first detected in Brazil in 2015 and then rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection was correlated with severe congenital malformations in newborns from infected mothers, as well as with Guillain-Barré syndrome in adults. Although the number of infected people has declined in the affected countries lately, the development of a vaccine for ZIKV is of great importance to avoid the future resurgence of the virus in endemic areas or the future spread to currently non-endemic regions. Among many different platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since tridimensional particles mimicking the virus – but lacking its genome – can be produced and present the antigen in a repetitive way, potentially eliciting robust immune responses. In this work, we demonstrated the generation of stably transfected HEK293 cells constitutively expressing Zika VLPs. Small-scale shake flask studies using a stable cell pool enriched by Fluorescence-Activated Cell Sorting (FACS) showed that daily medium exchange (intermittent perfusion) significantly enhances viable cell density and VLP production (∼4-fold) over batch cultures. Continuous perfusion in a controlled bioreactor coupled to an ATF-2 cell retention device resulted in maximum VLP titers similar to those obtained under small-scale intermittent perfusion. Our results show that the use of cell lines constitutively expressing Zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. |
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