Your browser doesn't support javascript.
loading
Impact of a blood-stage vaccine on Plasmodium vivax malaria.
Hou, Mimi M; Barrett, Jordan R; Themistocleous, Yrene; Rawlinson, Thomas A; Diouf, Ababacar; Martinez, Francisco J; Nielsen, Carolyn M; Lias, Amelia M; King, Lloyd D W; Edwards, Nick J; Greenwood, Nicola M; Kingham, Lucy; Poulton, Ian D; Khozoee, Baktash; Goh, Cyndi; Mac Lochlainn, Dylan J; Salkeld, Jo; Guilotte-Blisnick, Micheline; Huon, Christèle; Mohring, Franziska; Reimer, Jenny M; Chauhan, Virander S; Mukherjee, Paushali; Biswas, Sumi; Taylor, Iona J; Lawrie, Alison M; Cho, Jee-Sun; Nugent, Fay L; Long, Carole A; Moon, Robert W; Miura, Kazutoyo; Silk, Sarah E; Chitnis, Chetan E; Minassian, Angela M; Draper, Simon J.
Afiliación
  • Hou MM; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
  • Barrett JR; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Themistocleous Y; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
  • Rawlinson TA; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Diouf A; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Martinez FJ; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Nielsen CM; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.
  • Lias AM; Unité de Biologie de Plasmodium et Vaccins, Institut Pasteur, Université Paris Cité, 25-28 Rue du Dr Roux, 75015 Paris, France.
  • King LDW; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
  • Edwards NJ; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Greenwood NM; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
  • Kingham L; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Poulton ID; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, 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; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Salkeld J; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Guilotte-Blisnick M; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Huon C; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Mohring F; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Reimer JM; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
  • Chauhan VS; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Mukherjee P; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
  • Biswas S; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Taylor IJ; Unité de Biologie de Plasmodium et Vaccins, Institut Pasteur, Université Paris Cité, 25-28 Rue du Dr Roux, 75015 Paris, France.
  • Lawrie AM; Unité de Biologie de Plasmodium et Vaccins, Institut Pasteur, Université Paris Cité, 25-28 Rue du Dr Roux, 75015 Paris, France.
  • Cho JS; Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
  • Nugent FL; Novavax AB, Kungsgatan 109, SE-753 18, Uppsala, Sweden.
  • Long CA; International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
  • Moon RW; Multi-Vaccines Development Program, New Delhi, India.
  • Miura K; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Silk SE; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Chitnis CE; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
  • Minassian AM; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
  • Draper SJ; The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
medRxiv ; 2022 May 30.
Article en En | MEDLINE | ID: mdl-35664997
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 .
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: MedRxiv Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: MedRxiv Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido