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Vaccination with Plasmodium vivax Duffy-binding protein inhibits parasite growth during controlled human malaria infection.

ABSTRACT: There are no licensed vaccines against Plasmodium vivax. We conducted two phase 1/2a clinical trials to assess two vaccines targeting P. vivax Duffy-binding protein region II (PvDBPII). Recombinant viral vaccines using chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) vectors as well as a protein and adjuvant formulation (PvDBPII/Matrix-M) were tested in both a standard and a delayed dosing regimen. Volunteers underwent controlled human malaria infection (CHMI) after their last vaccination, alongside unvaccinated controls. Efficacy was assessed by comparisons of parasite multiplication rates in the blood. PvDBPII/Matrix-M, given in a delayed dosing regimen, elicited the highest antibody responses and reduced the mean parasite multiplication rate after CHMI by 51% (n = 6) compared with unvaccinated controls (n = 13), whereas no other vaccine or regimen affected parasite growth. Both viral-vectored and protein vaccines were well tolerated and elicited expected, short-lived adverse events. Together, these results support further clinical evaluation of the PvDBPII/Matrix-M P. vivax vaccine.

SUBMITTER: Hou MM

PROVIDER: S-EPMC7615121 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Vaccination with Plasmodium vivax Duffy-binding protein inhibits parasite growth during controlled human malaria infection.

Hou Mimi M MM Barrett Jordan R JR Themistocleous Yrene Y Rawlinson Thomas A TA Diouf Ababacar A Martinez Francisco J FJ Nielsen Carolyn M CM Lias Amelia M AM King Lloyd D W LDW Edwards Nick J NJ Greenwood Nicola M NM Kingham Lucy L Poulton Ian D ID Khozoee Baktash B Goh Cyndi C Hodgson Susanne H SH Mac Lochlainn Dylan J DJ Salkeld Jo J Guillotte-Blisnick Micheline M Huon Christèle C Mohring Franziska F Reimer Jenny M JM Chauhan Virander S VS Mukherjee Paushali P Biswas Sumi S Taylor Iona J IJ Lawrie Alison M AM Cho Jee-Sun JS Nugent Fay L FL Long Carole A CA Moon Robert W RW Miura Kazutoyo K Silk Sarah E SE Chitnis Chetan E CE Minassian Angela M AM Draper Simon J SJ

Science translational medicine 20230712 704

There are no licensed vaccines against Plasmodium vivax. We conducted two phase 1/2a clinical trials to assess two vaccines targeting P. vivax Duffy-binding protein region II (PvDBPII). Recombinant viral vaccines using chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) vectors as well as a protein and adjuvant formulation (PvDBPII/Matrix-M) were tested in both a standard and a delayed dosing regimen. Volunteers underwent controlled human malaria infection (C ...[more]

PMID: 37437014

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Project description:BackgroundThe Plasmodium vivax Duffy Binding Protein (PvDBP) is a key target of naturally acquired immunity. However, region II of PvDBP, which contains the receptor-binding site, is highly polymorphic. The natural acquisition of antibodies to different variants of PvDBP region II (PvDBPII), including the AH, O, P and Sal1 alleles, the central region III-V (PvDBPIII-V), and P. vivax Erythrocyte Binding Protein region II (PvEBPII) and their associations with risk of clinical P. vivax malaria are not well understood.MethodologyTotal IgG and IgG subclasses 1, 2, and 3 that recognize four alleles of PvDBPII (AH, O, P, and Sal1), PvDBPIII-V and PvEBPII were measured in samples collected from a cohort of 1 to 3 year old Papua New Guinean (PNG) children living in a highly endemic area of PNG. The levels of binding inhibitory antibodies (BIAbs) to PvDBPII (AH, O, and Sal1) were also tested in a subset of children. The association of presence of IgG with age, cumulative exposure (measured as the product of age and malaria infections during follow-up) and prospective risk of clinical malaria were evaluated.ResultsThe increase in antigen-specific total IgG, IgG1, and IgG3 with age and cumulative exposure was only observed for PvDBPII AH and PvEBPII. High levels of total IgG and predominant subclass IgG3 specific for PvDBPII AH were associated with decreased incidence of clinical P. vivax episodes (aIRR = 0.56-0.68, P≤0.001-0.021). High levels of total IgG and IgG1 to PvEBPII correlated strongly with protection against clinical vivax malaria compared with IgGs against all PvDBPII variants (aIRR = 0.38, P<0.001). Antibodies to PvDBPII AH and PvEBPII showed evidence of an additive effect, with a joint protective association of 70%.ConclusionAntibodies to the key parasite invasion ligands PvDBPII and PvEBPII are good correlates of protection against P. vivax malaria in PNG. This further strengthens the rationale for inclusion of PvDBPII in a recombinant subunit vaccine for P. vivax malaria and highlights the need for further functional studies to determine the potential of PvEBPII as a component of a subunit vaccine for P. vivax malaria.

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Vaccination with Plasmodium vivax Duffy-binding protein inhibits parasite growth during controlled human malaria infection.

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Vaccination with <i>Plasmodium vivax</i> Duffy-binding protein inhibits parasite growth during controlled human malaria infection.

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Vaccination with Plasmodium vivax Duffy-binding protein inhibits parasite growth during controlled human malaria infection.

Publications

Vaccination with &lt;i&gt;Plasmodium vivax&lt;/i&gt; Duffy-binding protein inhibits parasite growth during controlled human malaria infection.

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OmicsDI is part of the ELIXIR infrastructure

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Vaccination with <i>Plasmodium vivax</i> Duffy-binding protein inhibits parasite growth during controlled human malaria infection.