Rapid Fire Presentation 8th International Conference on Plasmodium vivax Research 2022

First Plasmodium vivax malaria vaccine candidate to show in vivo efficacy against a blood-stage P. vivax Controlled Human Malaria challenge in UK adults (#205)

Mimi M Hou 1 , Jordan R Barrett 2 , Sarah E Silk 2 , Carolyn M Nielsen 2 , Amelia Lias 2 , Nick J Edwards 3 , Nicola Greenwood 1 , Yrene Themistocleous 1 , Thomas Rawlinson 1 , Fernando Ramos Lopez 1 , Jee-Sun Cho 1 , Fay L Nugent 1 , Lucy Kingham-Page 1 , Alison M Lawrie 1 , Paushali Mukherjee 4 , Virander S Chauhan 5 , Francisco Martinez 6 , Micheline Guilotte-Blisnick 6 , Christele Huon 6 , Jenny M Reimer 7 , Chetan E Chitnis 6 , Simon J Draper 2 , Angela M Minassian 1
  1. Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK
  2. Department of Biochemistry, University of Oxford, Oxford, UK
  3. Jenner Institute, University of Oxford, Oxford, UK
  4. Multi-Vaccines Development Program, New Delhi, India
  5. International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
  6. Unité de Biologie de Plasmodium et Vaccins, Institut Pasteur, Paris, France
  7. Novavax AB, Uppsala, Sweden

Background

Invasion of reticulocytes by P. vivax parasites is mediated through interaction between the Duffy-binding protein (PvDBP) and Duffy antigen on reticulocytes. Region II within PvDBP (PvDBP_RII) is the domain that binds Duffy antigen, indicating its potential as a target for vaccination. A blood-stage P. vivax Controlled Human Malaria Infection (CHMI) model has been developed in Oxford (UK)1, enabling the testing of vaccine efficacy by CHMI.

Methods

Two formulations of vaccines targeting PvDBP_RII, a viral-vectored2 and a protein-in-adjuvant formulation3, were tested for safety, immunogenicity and efficacy in Phase I/IIa trials in healthy UK adults. The viral-vectored vaccines were administered at 0, 2 months (ChAd63, MVA) or 0, 17, 19 months (ChAd63, ChAd63, MVA). The protein vaccine PvDBP_RII in Matrix-M™ adjuvant (Novavax AB®) (DBP/M-M) was administered in a monthly regimen (0, 1, 2 months) or delayed dosing regimen (0, 1, 14 months). Delayed regimens were necessitated due to trial halts during the pandemic. Volunteers underwent CHMI at 1 month following their last vaccination in parallel with unvaccinated controls. Efficacy was assessed by comparison of the blood-stage parasite multiplication rate (PMR) during CHMI, with parasitaemia measured by qPCR.

Results

Both vaccine formulations were safe and immunogenic. The delayed dosing regimen of DBP/M-M elicited the strongest anti-PvDBP_RII-specific antibody response and following CHMI, demonstrated an average 47% reduction in PMR (95% CI 20-74%) compared to unvaccinated controls. Other vaccine regimens tested did not demonstrate a significant impact on parasite growth.

Conclusions

The DBP/M-M vaccine administered in a delayed dosing regimen demonstrated a significant reduction in parasite growth following blood-stage CHMI, and is the first P. vivax vaccine to show in vivo impact on parasitaemia in humans. The improvement in efficacy of this vaccine when given in a delayed rather than monthly dosing regimen highlights the importance of optimising timing in vaccination regimens.

  1. Minassian AM, et al. Controlled human malaria infection with a clone of Plasmodium vivax with high-quality genome assembly. JCI Insight. 2021 Dec 8;6(23):e152465.
  2. Payne RO, et al. Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies. JCI Insight. 2017 Jun 15;2(12):e93683.
  3. Singh K, et al. Malaria vaccine candidate based on Duffy-binding protein elicits strain transcending functional antibodies in a Phase I trial. NPJ Vaccines. 2018 Sep 28;3:48.