Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination
<p><strong>Background:</strong> 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-sta...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Cell Press
2021
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| _version_ | 1826310833458642944 |
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| author | Minassian, AM Silk, SE Barrett, JR Nielsen, CM Miura, K Diouf, A Loos, C Fallon, JK Michell, AR White, MT Edwards, NJ Poulton, ID Mitton, CH Payne, RO Marks, M Maxwell-Scott, H Querol-Rubiera, A Bisnauthsing, K Batra, R Ogrina, T Brendish, NJ Themistocleous, Y Rawlinson, TA Ellis, KJ Quinkert, D Baker, M Lopez Ramon, R Ramos Lopez, F Barfod, L Folegatti, PM Silman, D Datoo, M Taylor, IJ Jin, J Pulido, D Douglas, AD de Jongh, WA Smith, R Berrie, E Noe, AR Diggs, CL Soisson, LA Ashfield, R Faust, SN Goodman, AL Lawrie, AM Nugent, FL Alter, G Long, CA Draper, SJ |
| author_facet | Minassian, AM Silk, SE Barrett, JR Nielsen, CM Miura, K Diouf, A Loos, C Fallon, JK Michell, AR White, MT Edwards, NJ Poulton, ID Mitton, CH Payne, RO Marks, M Maxwell-Scott, H Querol-Rubiera, A Bisnauthsing, K Batra, R Ogrina, T Brendish, NJ Themistocleous, Y Rawlinson, TA Ellis, KJ Quinkert, D Baker, M Lopez Ramon, R Ramos Lopez, F Barfod, L Folegatti, PM Silman, D Datoo, M Taylor, IJ Jin, J Pulido, D Douglas, AD de Jongh, WA Smith, R Berrie, E Noe, AR Diggs, CL Soisson, LA Ashfield, R Faust, SN Goodman, AL Lawrie, AM Nugent, FL Alter, G Long, CA Draper, SJ |
| author_sort | Minassian, AM |
| collection | OXFORD |
| description | <p><strong>Background:</strong> 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 <i>Plasmodium falciparum</i>.</p>
<p><strong>Methods:</strong> We undertook a phase I/IIa clinical trial in healthy adults in the United Kingdom of the RH5.1 recombinant protein vaccine, targeting the <i>P. falciparum</i> reticulocyte-binding protein homolog 5 (RH5), formulated in AS01<sub>B</sub> adjuvant. We assessed safety, immunogenicity, and efficacy against blood-stage CHMI. Trial registered at ClinicalTrials.gov, NCT02927145.</p>
<p><strong>Findings:</strong> The RH5.1/AS01<sub>B</sub> 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 <i>P. falciparum</i>, 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 <i>in vitro</i> using purified immunoglobulin G (IgG) antibody strongly correlates with <i>in vivo</i> 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.</p>
<p><strong>Conclusions:</strong> Our data provide a new framework to guide rational design and delivery of next-generation vaccines to protect against malaria disease.</p>
<p><strong>Funding:</strong> This study was supported by USAID, UK MRC, Wellcome Trust, NIAID, and the NIHR Oxford-BRC.</p> |
| first_indexed | 2024-03-07T07:59:21Z |
| format | Journal article |
| id | oxford-uuid:aa78d236-5f7e-43ad-8d74-87af98c15324 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:59:21Z |
| publishDate | 2021 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:aa78d236-5f7e-43ad-8d74-87af98c153242023-09-12T13:38:52ZReduced blood-stage malaria growth and immune correlates in humans following RH5 vaccinationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:aa78d236-5f7e-43ad-8d74-87af98c15324EnglishSymplectic ElementsCell Press2021Minassian, AMSilk, SEBarrett, JRNielsen, CMMiura, KDiouf, ALoos, CFallon, JKMichell, ARWhite, MTEdwards, NJPoulton, IDMitton, CHPayne, ROMarks, MMaxwell-Scott, HQuerol-Rubiera, ABisnauthsing, KBatra, ROgrina, TBrendish, NJThemistocleous, YRawlinson, TAEllis, KJQuinkert, DBaker, MLopez Ramon, RRamos Lopez, FBarfod, LFolegatti, PMSilman, DDatoo, MTaylor, IJJin, JPulido, DDouglas, ADde Jongh, WASmith, RBerrie, ENoe, ARDiggs, CLSoisson, LAAshfield, RFaust, SNGoodman, ALLawrie, AMNugent, FLAlter, GLong, CADraper, SJ<p><strong>Background:</strong> 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 <i>Plasmodium falciparum</i>.</p> <p><strong>Methods:</strong> We undertook a phase I/IIa clinical trial in healthy adults in the United Kingdom of the RH5.1 recombinant protein vaccine, targeting the <i>P. falciparum</i> reticulocyte-binding protein homolog 5 (RH5), formulated in AS01<sub>B</sub> adjuvant. We assessed safety, immunogenicity, and efficacy against blood-stage CHMI. Trial registered at ClinicalTrials.gov, NCT02927145.</p> <p><strong>Findings:</strong> The RH5.1/AS01<sub>B</sub> 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 <i>P. falciparum</i>, 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 <i>in vitro</i> using purified immunoglobulin G (IgG) antibody strongly correlates with <i>in vivo</i> 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.</p> <p><strong>Conclusions:</strong> Our data provide a new framework to guide rational design and delivery of next-generation vaccines to protect against malaria disease.</p> <p><strong>Funding:</strong> This study was supported by USAID, UK MRC, Wellcome Trust, NIAID, and the NIHR Oxford-BRC.</p> |
| spellingShingle | Minassian, AM Silk, SE Barrett, JR Nielsen, CM Miura, K Diouf, A Loos, C Fallon, JK Michell, AR White, MT Edwards, NJ Poulton, ID Mitton, CH Payne, RO Marks, M Maxwell-Scott, H Querol-Rubiera, A Bisnauthsing, K Batra, R Ogrina, T Brendish, NJ Themistocleous, Y Rawlinson, TA Ellis, KJ Quinkert, D Baker, M Lopez Ramon, R Ramos Lopez, F Barfod, L Folegatti, PM Silman, D Datoo, M Taylor, IJ Jin, J Pulido, D Douglas, AD de Jongh, WA Smith, R Berrie, E Noe, AR Diggs, CL Soisson, LA Ashfield, R Faust, SN Goodman, AL Lawrie, AM Nugent, FL Alter, G Long, CA Draper, SJ Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination |
| title | Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination |
| title_full | Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination |
| title_fullStr | Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination |
| title_full_unstemmed | Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination |
| title_short | Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination |
| title_sort | reduced blood stage malaria growth and immune correlates in humans following rh5 vaccination |
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