Pré-Publication, Document De Travail (Preprint/Prepublication) Année : 2022

Impact of a blood-stage vaccine on Plasmodium vivax malaria

Mimi Hou
Jordan Barrett
Carolyn Nielsen
Amelia Lias
Lloyd King
  • Fonction : Auteur
Nick Edwards
Nicola Greenwood
  • Fonction : Auteur
Lucy Kingham
  • Fonction : Auteur
Ian Poulton
Baktash Khozoee
Cyndi Goh
Dylan Mac Lochlainn
Jo Salkeld
Jenny Reimer
Paushali Mukherjee
Sumi Biswas
Iona Taylor
Alison Lawrie
  • Fonction : Auteur
Jee-Sun Cho
  • Fonction : Auteur
Fay Nugent
  • Fonction : Auteur
Carole Long
Kazutoyo Miura
  • Fonction : Auteur
Sarah Silk
Angela Minassian
Simon Draper

Résumé

Abstract Background There are no licensed vaccines against Plasmodium vivax , the most common cause of malaria outside of Africa. Methods We conducted two Phase I/IIa clinical trials to assess the safety, immunogenicity and efficacy of two vaccines targeting region II of P. vivax Duffy-binding protein (PvDBPII). Recombinant viral vaccines (using ChAd63 and MVA vectors) were administered at 0, 2 months or in a delayed dosing regimen (0, 17, 19 months), whilst a protein/adjuvant formulation (PvDBPII/Matrix-M™) was administered monthly (0, 1, 2 months) or in a delayed dosing regimen (0, 1, 14 months). Delayed regimens were due to trial halts during the COVID-19 pandemic. Volunteers underwent heterologous controlled human malaria infection (CHMI) with blood-stage P. vivax parasites at 2-4 weeks following their last vaccination, alongside unvaccinated controls. Efficacy was assessed by comparison of parasite multiplication rate (PMR) in blood post-CHMI, modelled from parasitemia measured by quantitative polymerase-chain-reaction (qPCR). Results Thirty-two volunteers were enrolled and vaccinated (n=16 for each vaccine). No safety concerns were identified. PvDBPII/Matrix-M™, given in the delayed dosing regimen, elicited the highest antibody responses and reduced the mean PMR following CHMI by 51% (range 36-66%; n=6) compared to unvaccinated controls (n=13). No other vaccine or regimen impacted parasite growth. In vivo growth inhibition of blood-stage P. vivax correlated with functional antibody readouts of vaccine immunogenicity. Conclusions Vaccination of malaria-naïve adults with a delayed booster regimen of PvDBPII/ Matrix-M™ significantly reduces the growth of blood-stage P. vivax . Funded by the European Commission and Wellcome Trust; VAC069, VAC071 and VAC079 ClinicalTrials.gov numbers NCT03797989 , NCT04009096 and NCT04201431 .
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pasteur-04117002 , version 1 (05-06-2023)

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Mimi Hou, Jordan Barrett, Yrene Themistocleous, Thomas Rawlinson, Ababacar Diouf, et al.. Impact of a blood-stage vaccine on Plasmodium vivax malaria. 2022. ⟨pasteur-04117002⟩

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