Vaccination with <i>Plasmodium vivax</i> Duffy-binding protein inhibits parasite growth during controlled human malaria infection
Mimi M. Hou, Jordan R. Barrett, Yrene Themistocleous, Thomas A. Rawlinson, Ababacar Diouf, Francisco José Martínez Martínez, Carolyn M. Nielsen, Amelia M. Lias, Lloyd D. W. King, Nick J. Edwards, Nicola M. Greenwood, Lucy Kingham, Ian Poulton, Baktash Khozoee, Cyndi Goh, Susanne H. Hodgson, Dylan J. Mac Lochlainn, Jo Salkeld, Micheline Guillotte-Blisnick, Christèle Huon, Franziska Mohring, Jenny M. Reimer, Virander S. Chauhan, Paushali Mukherjee, Sumi Biswas, Iona J. Taylor, Alison M. Lawrie, Jee-Sun Cho, Fay L. Nugent, Carole A. Long, Robert W. Moon, Kazutoyo Miura, Sarah E. Silk, Chetan E. Chitnis, Angela M. Minassian, Simon J. Draper
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.