Mapping functional humoral correlates of protection against malaria challenge following RTS,S/AS01 vaccination
Rattachement africain : us, be, nl. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Vaccine development has the potential to be accelerated by coupling tools such as systems immunology analyses and controlled human infection models to define the protective efficacy of prospective immunogens without expensive and slow phase 2b/3 vaccine studies. Among human challenge models, controlled human malaria infection trials have long been used to evaluate candidate vaccines, and RTS,S/AS01 is the most advanced malaria vaccine candidate, reproducibly demonstrating 40 to 80% protection in human challenge studies in malaria-naïve individuals. Although antibodies are critical for protection after RTS,S/AS01 vaccination, antibody concentrations are inconsistently associated with protection across studies, and the precise mechanism(s) by which vaccine-induced antibodies provide protection remains enigmatic. Using a comprehensive systems serological profiling platform, the humoral correlates of protection against malaria were identified and validated across multiple challenge studies. Rather than antibody concentration, qualitative functional humoral features robustly predicted protection from infection across vaccine regimens. Despite the functional diversity of vaccine-induced immune responses across additional RTS,S/AS01 vaccine studies, the same antibody features, antibody-mediated phagocytosis and engagement of Fc gamma receptor 3A (FCGR3A), were able to predict protection across two additional human challenge studies. Functional validation using monoclonal antibodies confirmed the protective role of Fc-mediated antibody functions in restricting parasite infection both in vitro and in vivo, suggesting that these correlates may mechanistically contribute to parasite restriction and can be used to guide the rational design of an improved vaccine against malaria.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Mapping functional humoral correlates of protection against malaria challenge following RTS,S/AS01 vaccination
- Date Crossref
- 22/07/2020
- Éditeur
- American Association for the Advancement of Science (AAAS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Ragon Institute of MGH pays non établi dans la noticeÉtablissement de santé
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Massachusetts Institute of Technology Department of Biological Engineering pays non établi dans la noticeUniversité ou école supérieure
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Dartmouth College pays non établi dans la noticeUniversité ou école supérieure
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U.S. President's Malaria Initiative pays non établi dans la noticeInstitution
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GlaxoSmithKline (Belgium) pays non établi dans la noticeEntreprise
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Johns Hopkins University pays non établi dans la noticeUniversité ou école supérieure
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Walter Reed Army Institute of Research Malaria Vaccine Branch pays non établi dans la noticeOrganisme public
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Janssen (Netherlands) pays non établi dans la noticeEntreprise
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Broad Institute pays non établi dans la noticeOrganisation à but non lucratif
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Brigham and Women's Hospital Department of Medicine pays non établi dans la noticeÉtablissement de santé
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Howard Hughes Medical Institute pays non établi dans la noticeStructure de recherche
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Allen Institute pays non établi dans la noticeOrganisation à but non lucratif
Ragon Institute of MGH, Department of Biological Engineering — Massachusetts Institute of Technology et Dartmouth College, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.