Ulrike Wille-Reece

Identification of RTS,S/AS01 vaccine–induced humoral biomarkers predictive of protection against controlled human malaria infection

Rachel L. Spreng, Kelly E. Seaton, Lin Lin, Gillian Q. Horn et autres

BACKGROUNDThe mechanism(s) responsible for the efficacy of WHO-recommended malaria vaccine RTS,S/AS01 are not completely understood. We previously identified RTS,S vaccine-induced Plasmodium falciparum circumsporozoite protein-specific (PfCSP-specific) antibody measures associated with protection from controlled human malaria infection (CHMI). Here, we tested the protection-predicting capability …

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A candidate antibody drug for prevention of malaria

Katherine L. Williams, Steve Guerrero, Yevel Flores-García, Dongkyoon Kim et autres

Over 75% of malaria-attributable deaths occur in children under the age of 5 years. However, the first malaria vaccine recommended by the World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. Complementary strategies, including monoclonal antibodies, will be important …

us, be (code pays fourni par la source)

A candidate antibody drug for prevention of malaria.

Katherine L. Williams, Anthony Guerrero, Yevel Flores-García, Dongkyoon Kim et autres

Plasmablast human antibody repertoire sequences from volunteers in a malaria vaccine (RTS,S) clinical trial with sequence and donor annotations

A candidate antibody drug for prevention of malaria.

Katherine L. Williams, Anthony Guerrero, Yevel Flores-García, Dongkyoon Kim et autres

Plasmablast human antibody repertoire sequences from volunteers in a malaria vaccine (RTS,S) clinical trial with sequence and donor annotations

An antibody drug engineered for prevention of malaria in global populations

Katherine L. Williams, Steve Guerrero, Yevel Flores-García, Kayla Andrews et autres

Abstract Over 80% of malaria-attributable deaths are in children under five. However, the only malaria vaccine recommended by the World Health Organization (WHO) for paediatric use, Mosquirix™, has limited efficacy. Complementary strategies, like monoclonal antibodies (mAbs), will be required to eradicate malaria. …

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A tool for evaluating heterogeneity in avidity of polyclonal antibodies

Kan Li, Michael Dodds, Rachel L. Spreng, Milite Abraha et autres

Diversity in specificity of polyclonal antibody (pAb) responses is extensively investigated in vaccine efficacy or immunological evaluations, but the heterogeneity in antibody avidity is rarely probed as convenient tools are lacking. Here we have developed a polyclonal antibodies avidity resolution tool (PAART) …

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Delayed fractional dosing with RTS,S/AS01 improves humoral immunity to malaria via a balance of polyfunctional NANP6- and Pf16-specific antibodies

Jishnu Das, Jonathan K. Fallon, Timothy C. Yu, Ashlin R. Michell et autres

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Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection

Kelly E. Seaton, Rachel L. Spreng, Milite Abraha, Matthew Reichartz et autres

RTS,S/AS01 is an advanced pre-erythrocytic malaria vaccine candidate with demonstrated vaccine efficacy up to 86.7% in controlled human malaria infection (CHMI) studies; however, reproducible immune correlates of protection (CoP) are elusive. To identify candidates of humoral correlates of vaccine mediated protection, we …

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Comprehensive Data Integration Approach to Assess Immune Responses and Correlates of RTS,S/AS01-Mediated Protection From Malaria Infection in Controlled Human Malaria Infection Trials

William C. Young, Lindsay N. Carpp, Sidhartha Chaudhury, Jason A. Regules et autres

RTS,S/AS01 (GSK) is the world's first malaria vaccine. However, despite initial efficacy of almost 70% over the first 6 months of follow-up, efficacy waned over time. A deeper understanding of the immune features that contribute to RTS,S/AS01-mediated protection could be beneficial for …

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Magnitude, Specificity, and Avidity of Sporozoite-Specific Antibodies Associate With Protection Status and Distinguish Among RTS,S/AS01 Dose Regimens

S. Moses Dennison, Matthew Reichartz, Milite Abraha, Rachel L. Spreng et autres

Abstract Background The malaria vaccine, RTS,S/AS01, demonstrated an enhanced efficacy (86.7%) in a delayed third fractional dose (0.1.7Fx) regimen in controlled human malaria infection trials compared with a standard full-dose (0.1.2) regimen (62.5%). To understand the humoral component of the RTS,S/AS01 vaccine-induced …

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Mapping functional humoral correlates of protection against malaria challenge following RTS,S/AS01 vaccination

Todd J. Suscovich, Jonathan K. Fallon, Jishnu Das, Allison Demas et autres

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 …

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The Ratiometric Transcript Signature MX2/GPR183 Is Consistently Associated With RTS,S-Mediated Protection Against Controlled Human Malaria Infection

Ying Du, Ethan Thompson, Julius Müller, Joseph Valvo et autres

infection but determinants of protection and/or disease are unclear. Previously, anti-circumsporozoite protein (CSP) antibody titers and blood RNA signatures were associated with RTS,S/AS01 efficacy against controlled human malaria infection (CHMI). By analyzing host blood transcriptomes from five RTS,S vaccination CHMI studies, we …

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