Evidence map›Paper›PMID 40998768›Full record

ArticleNature communications2025

Development of clinical immunity to Plasmodium vivax following repeat controlled human malaria infection.

Mimi M Hou, Adam C Harding, Natalie M Barber, Prasun Kundu, Florian A Bach, Jo Salkeld, Yrene Themistocleous, Nicola M Greenwood, Jee-Sun Cho, Jordan R Barrett and 29 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03797989 (VAC069), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03797989 early_phase1completednot on this map

VAC069: A Clinical Study to Assess the Safety and Feasibility of Controlled Blood-stage Plasmodium Vivax Human Malaria Infection Through Experimental Inoculation of Cryopreserved Infected Erythrocytes in Healthy Malaria-naïve UK Adults

TypeinterventionalSponsorUniversity of OxfordRan2019 to 2022Enrolled19ConditionsMalaria, VivaxArmsP. vivax infected inoculum (parasitised red blood cells)
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Trial
  2. Review
  3. Frequent and genetically diverseResearch square · 2026
    Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

39 authors.

Mimi M HouThe Jenner Institute, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-8517-9147
Adam C Harding *Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-1479-959X
Natalie M Barber *Department of Biochemistry, University of Oxford, Oxford, UK.
Prasun KunduCambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Florian A BachInstitute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-0126-5516
Jo SalkeldThe Jenner Institute, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-7868-7071
Yrene ThemistocleousThe Jenner Institute, University of Oxford, Oxford, UK.
Nicola M GreenwoodThe Jenner Institute, University of Oxford, Oxford, UK.
Jee-Sun ChoThe Jenner Institute, University of Oxford, Oxford, UK.
Jordan R BarrettThe Jenner Institute, University of Oxford, Oxford, UK.
Fay L NugentThe Jenner Institute, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-6312-7293
Thomas A RawlinsonThe Jenner Institute, University of Oxford, Oxford, UK.
Susanne H HodgsonThe Jenner Institute, University of Oxford, Oxford, UK.
Baktash KhozoeeThe Jenner Institute, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-2470-3283
Dylan J Mac LochlainnThe Jenner Institute, University of Oxford, Oxford, UK.
Rachel E CowanThe Jenner Institute, University of Oxford, Oxford, UK.
Ian D PoultonThe Jenner Institute, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-6603-8461
Megan BakerThe Jenner Institute, University of Oxford, Oxford, UK.
Lucy KinghamThe Jenner Institute, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-7891-6359
Celia H MittonThe Jenner Institute, University of Oxford, Oxford, UK.
Abigail PlattThe Jenner Institute, University of Oxford, Oxford, UK.
Raquel Lopez RamonThe Jenner Institute, University of Oxford, Oxford, UK.
Fernando Ramos LopezThe Jenner Institute, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-9997-7879
Merin ThomasThe Jenner Institute, University of Oxford, Oxford, UK.
Katherine SkinnerThe Jenner Institute, University of Oxford, Oxford, UK.
Doris QuinkertThe Jenner Institute, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-4135-6452
Dimitra PipiniThe Jenner Institute, University of Oxford, Oxford, UK.
Amelia M LiasThe Jenner Institute, University of Oxford, Oxford, UK.
Martino BardelliThe Jenner Institute, University of Oxford, Oxford, UK.
Nick J EdwardsThe Jenner Institute, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-7030-7839
Francesca R DonnellanThe Jenner Institute, University of Oxford, Oxford, UK.
Sumi BiswasThe Jenner Institute, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-8507-7282
Julian C RaynerCambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-9835-1014
Carolyn M NielsenThe Jenner Institute, University of Oxford, Oxford, UK.
Sarah E SilkThe Jenner Institute, University of Oxford, Oxford, UK.
Simon J DraperThe Jenner Institute, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-9415-1357
Wiebke NahrendorfInstitute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-4503-8761
Philip J SpenceInstitute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK. pspence@ed.ac.uk.ORCID http://orcid.org/0000-0002-5506-2773
Angela M MinassianThe Jenner Institute, University of Oxford, Oxford, UK. angela.minassian@paediatrics.ox.ac.uk.ORCID http://orcid.org/0000-0001-7832-9824

Funding

EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) 733073Medical Research Council G1100086RCUK | Medical Research Council (MRC) G1100086Wellcome Trust 212336Wellcome Trust 226857Wellcome Trust (Wellcome) 212336/Z/18/Z
6 · The paper itself

Abstract

Clinical immunity to malaria can lead to asymptomatic infection, but the underlying mechanisms remain unclear. To examine the development of clinical immunity, we conducted a multi-cohort, repeat controlled human malaria infection (CHMI) study with Plasmodium vivax, and a heterologous rechallenge with P. falciparum (ClinicalTrials.gov NCT03797989). Malaria-naïve adults underwent CHMI up to three times, by administration of red blood cells infected with P. vivax PvW1 clone or P. falciparum 3D7 clone. Nineteen participants underwent primary CHMI with P. vivax, 12 returned for secondary homologous CHMI and 2 for tertiary homologous CHMI. Six participants who had completed P. vivax CHMI then underwent heterologous rechallenge with P. falciparum. We find that clinical immunity to P. vivax develops rapidly after a single CHMI, protecting participants against fever and laboratory abnormalities. This is underpinned by the attenuation of inflammatory cytokines and chemokines, as well as reduced coagulation and endothelium activation. In contrast, there is no evidence of anti-parasite immunity, suggesting that mechanisms of clinical immunity can operate independently of pathogen load to reduce the damage caused by malaria infection. In addition, we show that clinical immunity to P. vivax is parasite species-specific and provides no protection against CHMI with P. falciparum.

Indexed as

Malaria, FalciparumMalaria, VivaxPlasmodium vivaxAdultCohort StudiesCytokinesErythrocytesFemaleHumansMaleMiddle AgedPlasmodium falciparumYoung AdultCytokines

Identifiers

PMID40998768
PMCPMC12462441

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.