The effect of dosage on the protective efficacy of whole-sporozoite formulations for immunization against malaria

Detalhes bibliográficos
Autor(a) principal: Moita, Diana
Data de Publicação: 2023
Outros Autores: Rôla, Catarina, Nunes-Cabaço, Helena, Nogueira, Gonçalo, Maia, Teresa G., Othman, Ahmad Syibli, Franke-Fayard, Blandine, Janse, Chris J., Mendes, António M., Prudêncio, Miguel
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/61038
Resumo: © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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spelling The effect of dosage on the protective efficacy of whole-sporozoite formulations for immunization against malaria© The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Immunization with Plasmodium sporozoites, either attenuated or administered under the cover of an antimalarial drug, can induce strong protection against malaria in pre-clinical murine models, as well as in human trials. Previous studies have suggested that whole-sporozoite (WSpz) formulations based on parasites with longer liver stage development induce higher protection, but a comparative analysis of four different WSpz formulations has not been reported. We employed a rodent model of malaria to analyze the effect of immunization dosage on the protective efficacy of WSpz formulations consisting of (i) early liver arresting genetically attenuated parasites (EA-GAP) or (ii) radiation-attenuated sporozoites (RAS), (iii) late arresting GAP (LA-GAP), and (iv) sporozoites administered under chemoprophylaxis, that are eliminated upon release into the bloodstream (CPS). Our results show that, unlike all other WSpz formulations, EA-GAP fails to confer complete protection against an infectious challenge at any immunization dosage employed, suggesting that a minimum threshold of liver development is required to elicit fully effective immune responses. Moreover, while immunization with RAS, LA-GAP and CPS WSpz yields comparable, dosage-dependent protection, protection by EA-GAP WSpz peaks at an intermediate dosage and markedly decreases thereafter. In-depth immunological analyses suggest that effector CD8+ T cells elicited by EA-GAP WSpz immunization have limited developmental plasticity, with a potential negative impact on the functional versatility of memory cells and, thus, on protective immunity. Our findings point towards dismissing EA-GAP from prioritization for WSpz malaria vaccination and enhance our understanding of the complexity of the protection elicited by these WSpz vaccine candidates, guiding their future optimization.MP acknowledges the “la Caixa” Foundation for Grant HR21-848, the GSK OpenLab Foundation for grant TC269, and FCT for grant PTDC-SAU-INF-29550-2017. DM acknowledges FCT for grant SFRH/BD/144817/2019. A.S. Othman was supported by a Skim Latihan Akademik IPTA - SLAI (Ministry of Higher Education, Malaysia).Springer NatureRepositório da Universidade de LisboaMoita, DianaRôla, CatarinaNunes-Cabaço, HelenaNogueira, GonçaloMaia, Teresa G.Othman, Ahmad SyibliFranke-Fayard, BlandineJanse, Chris J.Mendes, António M.Prudêncio, Miguel2023-11-30T14:29:21Z20232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/61038engNPJ Vaccines. 2023 Nov 24;8(1):18210.1038/s41541-023-00778-92059-0105info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-04T01:20:16Zoai:repositorio.ul.pt:10451/61038Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:40:54.582411Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The effect of dosage on the protective efficacy of whole-sporozoite formulations for immunization against malaria
title The effect of dosage on the protective efficacy of whole-sporozoite formulations for immunization against malaria
spellingShingle The effect of dosage on the protective efficacy of whole-sporozoite formulations for immunization against malaria
Moita, Diana
title_short The effect of dosage on the protective efficacy of whole-sporozoite formulations for immunization against malaria
title_full The effect of dosage on the protective efficacy of whole-sporozoite formulations for immunization against malaria
title_fullStr The effect of dosage on the protective efficacy of whole-sporozoite formulations for immunization against malaria
title_full_unstemmed The effect of dosage on the protective efficacy of whole-sporozoite formulations for immunization against malaria
title_sort The effect of dosage on the protective efficacy of whole-sporozoite formulations for immunization against malaria
author Moita, Diana
author_facet Moita, Diana
Rôla, Catarina
Nunes-Cabaço, Helena
Nogueira, Gonçalo
Maia, Teresa G.
Othman, Ahmad Syibli
Franke-Fayard, Blandine
Janse, Chris J.
Mendes, António M.
Prudêncio, Miguel
author_role author
author2 Rôla, Catarina
Nunes-Cabaço, Helena
Nogueira, Gonçalo
Maia, Teresa G.
Othman, Ahmad Syibli
Franke-Fayard, Blandine
Janse, Chris J.
Mendes, António M.
Prudêncio, Miguel
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Moita, Diana
Rôla, Catarina
Nunes-Cabaço, Helena
Nogueira, Gonçalo
Maia, Teresa G.
Othman, Ahmad Syibli
Franke-Fayard, Blandine
Janse, Chris J.
Mendes, António M.
Prudêncio, Miguel
description © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
publishDate 2023
dc.date.none.fl_str_mv 2023-11-30T14:29:21Z
2023
2023-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/61038
url http://hdl.handle.net/10451/61038
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv NPJ Vaccines. 2023 Nov 24;8(1):182
10.1038/s41541-023-00778-9
2059-0105
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