Impact of a blood-stage vaccine on Plasmodium vivax malaria.

Autor:	Hou MM; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Barrett JR; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Themistocleous Y; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Rawlinson TA; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Diouf A; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA., Martinez FJ; Unité de Biologie de Plasmodium et Vaccins, Institut Pasteur, Université Paris Cité, 25-28 Rue du Dr Roux, 75015 Paris, France., Nielsen CM; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Lias AM; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., King LDW; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Edwards NJ; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Greenwood NM; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Kingham L; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Poulton ID; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Khozoee B; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Goh C; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Mac Lochlainn DJ; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Salkeld J; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Guilotte-Blisnick M; Unité de Biologie de Plasmodium et Vaccins, Institut Pasteur, Université Paris Cité, 25-28 Rue du Dr Roux, 75015 Paris, France., Huon C; Unité de Biologie de Plasmodium et Vaccins, Institut Pasteur, Université Paris Cité, 25-28 Rue du Dr Roux, 75015 Paris, France., Mohring F; Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK., Reimer JM; Novavax AB, Kungsgatan 109, SE-753 18, Uppsala, Sweden., Chauhan VS; International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India., Mukherjee P; Multi-Vaccines Development Program, New Delhi, India., Biswas S; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Taylor IJ; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Lawrie AM; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Cho JS; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Nugent FL; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Long CA; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA., Moon RW; Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK., Miura K; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA., Silk SE; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Chitnis CE; Unité de Biologie de Plasmodium et Vaccins, Institut Pasteur, Université Paris Cité, 25-28 Rue du Dr Roux, 75015 Paris, France., Minassian AM; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK., Draper SJ; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2022 May 30. Date of Electronic Publication: 2022 May 30.
DOI:	10.1101/2022.05.27.22275375
Abstrakt:	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 .
Databáze:	MEDLINE
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