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Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination.
Minassian, Angela M; Silk, Sarah E; Barrett, Jordan R; Nielsen, Carolyn M; Miura, Kazutoyo; Diouf, Ababacar; Loos, Carolin; Fallon, Jonathan K; Michell, Ashlin R; White, Michael T; Edwards, Nick J; Poulton, Ian D; Mitton, Celia H; Payne, Ruth O; Marks, Michael; Maxwell-Scott, Hector; Querol-Rubiera, Antonio; Bisnauthsing, Karen; Batra, Rahul; Ogrina, Tatiana; Brendish, Nathan J; Themistocleous, Yrene; Rawlinson, Thomas A; Ellis, Katherine J; Quinkert, Doris; Baker, Megan; Lopez Ramon, Raquel; Ramos Lopez, Fernando; Barfod, Lea; Folegatti, Pedro M; Silman, Daniel; Datoo, Mehreen; Taylor, Iona J; Jin, Jing; Pulido, David; Douglas, Alexander D; de Jongh, Willem A; Smith, Robert; Berrie, Eleanor; Noe, Amy R; Diggs, Carter L; Soisson, Lorraine A; Ashfield, Rebecca; Faust, Saul N; Goodman, Anna L; Lawrie, Alison M; Nugent, Fay L; Alter, Galit; Long, Carole A; Draper, Simon J.
Affiliation
  • Minassian AM; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Silk SE; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Barrett JR; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Nielsen CM; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Miura K; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.
  • Diouf A; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.
  • Loos C; The Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Fallon JK; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Michell AR; The Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • White MT; The Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Edwards NJ; Department of Parasites and Insect Vectors, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France.
  • Poulton ID; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Mitton CH; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Payne RO; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Marks M; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Maxwell-Scott H; Centre for Clinical Infection and Diagnostics Research, King's College London and Guy's & St Thomas' NHS Foundation Trust, Westminster Bridge Road, London SE1 7EH, UK.
  • Querol-Rubiera A; Centre for Clinical Infection and Diagnostics Research, King's College London and Guy's & St Thomas' NHS Foundation Trust, Westminster Bridge Road, London SE1 7EH, UK.
  • Bisnauthsing K; Centre for Clinical Infection and Diagnostics Research, King's College London and Guy's & St Thomas' NHS Foundation Trust, Westminster Bridge Road, London SE1 7EH, UK.
  • Batra R; Centre for Clinical Infection and Diagnostics Research, King's College London and Guy's & St Thomas' NHS Foundation Trust, Westminster Bridge Road, London SE1 7EH, UK.
  • Ogrina T; Centre for Clinical Infection and Diagnostics Research, King's College London and Guy's & St Thomas' NHS Foundation Trust, Westminster Bridge Road, London SE1 7EH, UK.
  • Brendish NJ; NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
  • Themistocleous Y; NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
  • Rawlinson TA; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Ellis KJ; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Quinkert D; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Baker M; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Lopez Ramon R; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Ramos Lopez F; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Barfod L; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Folegatti PM; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Silman D; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Datoo M; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Taylor IJ; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Jin J; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Pulido D; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Douglas AD; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • de Jongh WA; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Smith R; ExpreSion Biotechnologies, SCION-DTU Science Park, Agern Allé 1, Hørsholm 2970, Denmark.
  • Berrie E; Clinical BioManufacturing Facility, University of Oxford, Oxford OX3 7JT, UK.
  • Noe AR; Clinical BioManufacturing Facility, University of Oxford, Oxford OX3 7JT, UK.
  • Diggs CL; Leidos Life Sciences, Fredrick, MD, USA.
  • Soisson LA; USAID, 1300 Pennsylvania Ave. NW, Washington, DC 20004, USA.
  • Ashfield R; USAID, 1300 Pennsylvania Ave. NW, Washington, DC 20004, USA.
  • Faust SN; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Goodman AL; NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
  • Lawrie AM; Centre for Clinical Infection and Diagnostics Research, King's College London and Guy's & St Thomas' NHS Foundation Trust, Westminster Bridge Road, London SE1 7EH, UK.
  • Nugent FL; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Alter G; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
  • Long CA; The Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Draper SJ; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.
Med ; 2(6): 701-719.e19, 2021 06 11.
Article in En | MEDLINE | ID: mdl-34223402
ABSTRACT

BACKGROUND:

Development of an effective vaccine against the pathogenic blood-stage infection of human malaria has proved challenging, and no candidate vaccine has affected blood-stage parasitemia following controlled human malaria infection (CHMI) with blood-stage Plasmodium falciparum.

METHODS:

We undertook a phase I/IIa clinical trial in healthy adults in the United Kingdom of the RH5.1 recombinant protein vaccine, targeting the P. falciparum reticulocyte-binding protein homolog 5 (RH5), formulated in AS01B adjuvant. We assessed safety, immunogenicity, and efficacy against blood-stage CHMI. Trial registered at ClinicalTrials.gov, NCT02927145.

FINDINGS:

The RH5.1/AS01B formulation was administered using a range of RH5.1 protein vaccine doses (2, 10, and 50 µg) and was found to be safe and well tolerated. A regimen using a delayed and fractional third dose, in contrast to three doses given at monthly intervals, led to significantly improved antibody response longevity over ∼2 years of follow-up. Following primary and secondary CHMI of vaccinees with blood-stage P. falciparum, a significant reduction in parasite growth rate was observed, defining a milestone for the blood-stage malaria vaccine field. We show that growth inhibition activity measured in vitro using purified immunoglobulin G (IgG) antibody strongly correlates with in vivo reduction of the parasite growth rate and also identify other antibody feature sets by systems serology, including the plasma anti-RH5 IgA1 response, that are associated with challenge outcome.

CONCLUSIONS:

Our data provide a new framework to guide rational design and delivery of next-generation vaccines to protect against malaria disease.

FUNDING:

This study was supported by USAID, UK MRC, Wellcome Trust, NIAID, and the NIHR Oxford-BRC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Malaria, Falciparum / Malaria Vaccines / Malaria Type of study: Clinical_trials / Prognostic_studies Limits: Adult / Humans Language: En Journal: Med Year: 2021 Document type: Article Affiliation country: United kingdom
Fulltext
Add to My VHL
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Malaria, Falciparum / Malaria Vaccines / Malaria Type of study: Clinical_trials / Prognostic_studies Limits: Adult / Humans Language: En Journal: Med Year: 2021 Document type: Article Affiliation country: United kingdom