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

Mimi M Hou ORCID logo ; Jordan R Barrett ORCID logo ; Yrene Themistocleous ORCID logo ; Thomas A Rawlinson ; Ababacar Diouf ; Francisco J Martinez ORCID logo ; Carolyn M Nielsen ORCID logo ; Amelia M Lias ORCID logo ; Lloyd DW King ; Nick J Edwards ORCID logo ; +26 more... Nicola M Greenwood ; Lucy Kingham ; Ian D Poulton ORCID logo ; Baktash Khozoee ORCID logo ; Cyndi Goh ORCID logo ; Susanne H Hodgson ORCID logo ; Dylan J Mac Lochlainn ORCID logo ; Jo Salkeld ORCID logo ; Micheline Guillotte-Blisnick ; Christèle Huon ORCID logo ; Franziska Mohring ; Jenny M Reimer ORCID logo ; Virander S Chauhan ; Paushali Mukherjee ORCID logo ; Sumi Biswas ; Iona J Taylor ORCID logo ; Alison M Lawrie ; Jee-Sun Cho ; Fay L Nugent ORCID logo ; Carole A Long ORCID logo ; Robert W Moon ORCID logo ; Kazutoyo Miura ORCID logo ; Sarah E Silk ORCID logo ; Chetan E Chitnis ORCID logo ; Angela M Minassian ORCID logo ; Simon J Draper ORCID logo ; (2023) Vaccination with Plasmodium vivax Duffy-binding protein inhibits parasite growth during controlled human malaria infection. Science translational medicine, 15 (704). eadf1782-. ISSN 1946-6234 DOI: 10.1126/scitranslmed.adf1782
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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.


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