Yeast lysates carrying the nucleoprotein from measles virus vaccine as a novel subunit vaccine platform to deliver Plasmodium circumsporozoite antigen
Abstract Background Yeast cells represent an established bioreactor to produce recombinant proteins for subunit vaccine development. In addition, delivery of vaccine antigens directly within heat-inactivated yeast cells is attractive due to the adjuvancy provided by the yeast cell. In this study, Pi...
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ftdoajarticles:oai:doaj.org/article:9371923227ce4a7c95cf5436f6017c64 2023-05-15T15:18:39+02:00 Yeast lysates carrying the nucleoprotein from measles virus vaccine as a novel subunit vaccine platform to deliver Plasmodium circumsporozoite antigen Daria Jacob Claude Ruffie Chantal Combredet Pauline Formaglio Rogerio Amino Robert Ménard Frédéric Tangy Monica Sala 2017-06-01T00:00:00Z https://doi.org/10.1186/s12936-017-1908-7 https://doaj.org/article/9371923227ce4a7c95cf5436f6017c64 EN eng BMC http://link.springer.com/article/10.1186/s12936-017-1908-7 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-017-1908-7 1475-2875 https://doaj.org/article/9371923227ce4a7c95cf5436f6017c64 Malaria Journal, Vol 16, Iss 1, Pp 1-14 (2017) Plasmodium berghei Malaria vaccine CS antigen Pichia pastoris Yeast lysate Measles virus Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2017 ftdoajarticles https://doi.org/10.1186/s12936-017-1908-7 2022-12-31T10:50:46Z Abstract Background Yeast cells represent an established bioreactor to produce recombinant proteins for subunit vaccine development. In addition, delivery of vaccine antigens directly within heat-inactivated yeast cells is attractive due to the adjuvancy provided by the yeast cell. In this study, Pichia pastoris yeast lysates carrying the nucleoprotein (N) from the measles vaccine virus were evaluated as a novel subunit vaccine platform to deliver the circumsporozoite surface antigen (CS) of Plasmodium. When expressed in Pichia pastoris yeast, the N protein auto-assembles into highly multimeric ribonucleoparticles (RNPs). The CS antigen from Plasmodium berghei (PbCS) was expressed in Pichia pastoris yeast in fusion with N, generating recombinant PbCS-carrying RNPs in the cytoplasm of yeast cells. Results When evaluated in mice after 3–5 weekly subcutaneous injections, yeast lysates containing N-PbCS RNPs elicited strong anti-PbCS humoral responses, which were PbCS-dose dependent and reached a plateau by the pre-challenge time point. Protective efficacy of yeast lysates was dose-dependent, although anti-PbCS antibody titers were not predictive of protection. Multimerization of PbCS on RNPs was essential for providing benefit against infection, as immunization with monomeric PbCS delivered in yeast lysates was not protective. Three weekly injections with N-PbCS yeast lysates in combination with alum adjuvant produced sterile protection in two out of six mice, and significantly reduced parasitaemia in the other individuals from the same group. This parasitaemia decrease was of the same extent as in mice immunized with non-adjuvanted N-PbCS yeast lysates, providing evidence that the yeast lysate formulation did not require accessory adjuvants for eliciting efficient parasitaemia reduction. Conclusions This study demonstrates that yeast lysates are an attractive auto-adjuvant and efficient platform for delivering multimeric PbCS on measles N-based RNPs. By combining yeast lysates that carry RNPs with a large panel of ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 16 1 |
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English |
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Plasmodium berghei Malaria vaccine CS antigen Pichia pastoris Yeast lysate Measles virus Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Plasmodium berghei Malaria vaccine CS antigen Pichia pastoris Yeast lysate Measles virus Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Daria Jacob Claude Ruffie Chantal Combredet Pauline Formaglio Rogerio Amino Robert Ménard Frédéric Tangy Monica Sala Yeast lysates carrying the nucleoprotein from measles virus vaccine as a novel subunit vaccine platform to deliver Plasmodium circumsporozoite antigen |
topic_facet |
Plasmodium berghei Malaria vaccine CS antigen Pichia pastoris Yeast lysate Measles virus Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Yeast cells represent an established bioreactor to produce recombinant proteins for subunit vaccine development. In addition, delivery of vaccine antigens directly within heat-inactivated yeast cells is attractive due to the adjuvancy provided by the yeast cell. In this study, Pichia pastoris yeast lysates carrying the nucleoprotein (N) from the measles vaccine virus were evaluated as a novel subunit vaccine platform to deliver the circumsporozoite surface antigen (CS) of Plasmodium. When expressed in Pichia pastoris yeast, the N protein auto-assembles into highly multimeric ribonucleoparticles (RNPs). The CS antigen from Plasmodium berghei (PbCS) was expressed in Pichia pastoris yeast in fusion with N, generating recombinant PbCS-carrying RNPs in the cytoplasm of yeast cells. Results When evaluated in mice after 3–5 weekly subcutaneous injections, yeast lysates containing N-PbCS RNPs elicited strong anti-PbCS humoral responses, which were PbCS-dose dependent and reached a plateau by the pre-challenge time point. Protective efficacy of yeast lysates was dose-dependent, although anti-PbCS antibody titers were not predictive of protection. Multimerization of PbCS on RNPs was essential for providing benefit against infection, as immunization with monomeric PbCS delivered in yeast lysates was not protective. Three weekly injections with N-PbCS yeast lysates in combination with alum adjuvant produced sterile protection in two out of six mice, and significantly reduced parasitaemia in the other individuals from the same group. This parasitaemia decrease was of the same extent as in mice immunized with non-adjuvanted N-PbCS yeast lysates, providing evidence that the yeast lysate formulation did not require accessory adjuvants for eliciting efficient parasitaemia reduction. Conclusions This study demonstrates that yeast lysates are an attractive auto-adjuvant and efficient platform for delivering multimeric PbCS on measles N-based RNPs. By combining yeast lysates that carry RNPs with a large panel of ... |
format |
Article in Journal/Newspaper |
author |
Daria Jacob Claude Ruffie Chantal Combredet Pauline Formaglio Rogerio Amino Robert Ménard Frédéric Tangy Monica Sala |
author_facet |
Daria Jacob Claude Ruffie Chantal Combredet Pauline Formaglio Rogerio Amino Robert Ménard Frédéric Tangy Monica Sala |
author_sort |
Daria Jacob |
title |
Yeast lysates carrying the nucleoprotein from measles virus vaccine as a novel subunit vaccine platform to deliver Plasmodium circumsporozoite antigen |
title_short |
Yeast lysates carrying the nucleoprotein from measles virus vaccine as a novel subunit vaccine platform to deliver Plasmodium circumsporozoite antigen |
title_full |
Yeast lysates carrying the nucleoprotein from measles virus vaccine as a novel subunit vaccine platform to deliver Plasmodium circumsporozoite antigen |
title_fullStr |
Yeast lysates carrying the nucleoprotein from measles virus vaccine as a novel subunit vaccine platform to deliver Plasmodium circumsporozoite antigen |
title_full_unstemmed |
Yeast lysates carrying the nucleoprotein from measles virus vaccine as a novel subunit vaccine platform to deliver Plasmodium circumsporozoite antigen |
title_sort |
yeast lysates carrying the nucleoprotein from measles virus vaccine as a novel subunit vaccine platform to deliver plasmodium circumsporozoite antigen |
publisher |
BMC |
publishDate |
2017 |
url |
https://doi.org/10.1186/s12936-017-1908-7 https://doaj.org/article/9371923227ce4a7c95cf5436f6017c64 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 16, Iss 1, Pp 1-14 (2017) |
op_relation |
http://link.springer.com/article/10.1186/s12936-017-1908-7 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-017-1908-7 1475-2875 https://doaj.org/article/9371923227ce4a7c95cf5436f6017c64 |
op_doi |
https://doi.org/10.1186/s12936-017-1908-7 |
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Malaria Journal |
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16 |
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1 |
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1766348842196795392 |