Ultra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice

Abstract An effective vaccine would be a valuable tool for malaria control and elimination; however, the leading malaria vaccine in development, RTS,S/AS01, provided only partial protection in a Phase 3 trial. R21 is a next-generation RTS,S-like vaccine. We have previously shown in mice that R21 adm...

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Autores principales:	Katharine A. Collins, Florian Brod, Rebecca Snaith, Marta Ulaszewska, Rhea J. Longley, Ahmed M. Salman, Sarah C. Gilbert, Alexandra J. Spencer, David Franco, W. Ripley Ballou, Adrian V. S. Hill
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2049d091dd6f4297bcb5fc1522ae3a45
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spelling	oai:doaj.org-article:2049d091dd6f4297bcb5fc1522ae3a452021-12-02T15:49:53ZUltra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice10.1038/s41598-021-90290-82045-2322https://doaj.org/article/2049d091dd6f4297bcb5fc1522ae3a452021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90290-8https://doaj.org/toc/2045-2322Abstract An effective vaccine would be a valuable tool for malaria control and elimination; however, the leading malaria vaccine in development, RTS,S/AS01, provided only partial protection in a Phase 3 trial. R21 is a next-generation RTS,S-like vaccine. We have previously shown in mice that R21 administered in Matrix-M is highly immunogenic, able to elicit complete protection against sporozoite challenge, and can be successfully administered with TRAP based viral-vectors resulting in enhanced protection. In this study, we developed a novel, GMP-compatible purification process for R21, and evaluated the immunogenicity and protective efficacy of ultra-low doses of both R21 and RTS,S when formulated in AS01. We demonstrated that both vaccines are highly immunogenic and also elicit comparable high levels of protection against transgenic parasites in BALB/c mice. By lowering the vaccine dose there was a trend for increased immunogenicity and sterile protection, with the highest dose vaccine groups achieving the lowest efficacy (50% sterile protection). We also evaluated the ability to combine RTS,S/AS01 with TRAP based viral-vectors and observed concurrent induction of immune responses to both antigens with minimal interference when mixing the vaccines prior to administration. These studies suggest that R21 or RTS,S could be combined with viral-vectors for a multi-component vaccination approach and indicate that low dose vaccination should be fully explored in humans to maximize potential efficacy.Katharine A. CollinsFlorian BrodRebecca SnaithMarta UlaszewskaRhea J. LongleyAhmed M. SalmanSarah C. GilbertAlexandra J. SpencerDavid FrancoW. Ripley BallouAdrian V. S. HillNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katharine A. Collins Florian Brod Rebecca Snaith Marta Ulaszewska Rhea J. Longley Ahmed M. Salman Sarah C. Gilbert Alexandra J. Spencer David Franco W. Ripley Ballou Adrian V. S. Hill Ultra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice
description	Abstract An effective vaccine would be a valuable tool for malaria control and elimination; however, the leading malaria vaccine in development, RTS,S/AS01, provided only partial protection in a Phase 3 trial. R21 is a next-generation RTS,S-like vaccine. We have previously shown in mice that R21 administered in Matrix-M is highly immunogenic, able to elicit complete protection against sporozoite challenge, and can be successfully administered with TRAP based viral-vectors resulting in enhanced protection. In this study, we developed a novel, GMP-compatible purification process for R21, and evaluated the immunogenicity and protective efficacy of ultra-low doses of both R21 and RTS,S when formulated in AS01. We demonstrated that both vaccines are highly immunogenic and also elicit comparable high levels of protection against transgenic parasites in BALB/c mice. By lowering the vaccine dose there was a trend for increased immunogenicity and sterile protection, with the highest dose vaccine groups achieving the lowest efficacy (50% sterile protection). We also evaluated the ability to combine RTS,S/AS01 with TRAP based viral-vectors and observed concurrent induction of immune responses to both antigens with minimal interference when mixing the vaccines prior to administration. These studies suggest that R21 or RTS,S could be combined with viral-vectors for a multi-component vaccination approach and indicate that low dose vaccination should be fully explored in humans to maximize potential efficacy.
format	article
author	Katharine A. Collins Florian Brod Rebecca Snaith Marta Ulaszewska Rhea J. Longley Ahmed M. Salman Sarah C. Gilbert Alexandra J. Spencer David Franco W. Ripley Ballou Adrian V. S. Hill
author_facet	Katharine A. Collins Florian Brod Rebecca Snaith Marta Ulaszewska Rhea J. Longley Ahmed M. Salman Sarah C. Gilbert Alexandra J. Spencer David Franco W. Ripley Ballou Adrian V. S. Hill
author_sort	Katharine A. Collins
title	Ultra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice
title_short	Ultra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice
title_full	Ultra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice
title_fullStr	Ultra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice
title_full_unstemmed	Ultra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice
title_sort	ultra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2049d091dd6f4297bcb5fc1522ae3a45
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Ultra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice

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