Safety and efficacy of the blood-stage malaria vaccine RH5.1/Matrix-M in Burkina Faso: interim results of a double-blind, randomised, controlled, phase 2b trial in children

  1. Hamtandi M Natama
  2. Jo Salkeld
  3. Athanase Somé
  4. Seyi Soremekun
  5. Salou Diallo
  6. Ousmane Traoré
  7. Toussaint Rouamba
  8. Florence Ouédraogo
  9. Edouard Ouédraogo
  10. K Carine Sonia Daboné
  11. Nadine A Koné
  12. Z Michael John Compaoré
  13. Miguel Kafando
  14. Massa dit Achille Bonko
  15. Fabé Konaté
  16. Hermann Sorgho
  17. Carolyn M Nielsen
  18. Dimitra Pipini
  19. Ababacar Diouf
  20. Lloyd D W King
  21. Umesh Shaligram
  22. Carole A Long
  23. Jee-Sun Cho
  24. Alison M Lawrie
  25. Katherine Skinner
  26. Rachel Roberts
  27. Kazutoyo Miura
  28. John Bradley
  29. Sarah E Silk
  30. Simon J Draper
  31. Halidou Tinto
  32. Angela M Minassian

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Abstract

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  1. Version published to 10.1016/s1473-3099(24)00752-7
  2. PREreview

    This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/14176590.

    Does the introduction explain the objective of the research presented in the preprint? Partly The background and the literature are too narrow for the readers to get a comprehensive understanding. It might need to be expanded to cover different aspects of the study objectives in other parts of Africa's malaria vaccine.
    Are the methods well-suited for this research? Somewhat appropriate I want the authors to clarify the decisions made around the sample size. It is small for broader decisions. The control sample size is a great concern. Was this a pilot trial? Some headings might need to be readjustment such as "randomization and masking" to "randomization and allocation". Additionally, ITT is recommended as the main analysis instead of per protocol. Authors might want to clarify
    Are the conclusions supported by the data? Highly supported yes, the conclusion derived match the overall result of the study and seems to meet the intended objectives.
    Are the data presentations, including visualizations, well-suited to represent the data? Highly appropriate and clear Yes, the data is well presented using the cox-regression model and odd ratio. Moreover P-value and confidence intervals were reported properly. Visualization of the data using tables and graphs also easy to read and understand.
    How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Somewhat clearly They discussed their findings in addition to some study's strengths and limitations. Moreover, they provided strong recommendations for the forthcoming trials regarding the malaria vaccine.
    Is the preprint likely to advance academic knowledge? Highly likely the study significantly advances the existing knowledge regarding the application of the malaria vaccine in Africa including the development of an adjunct vaccine that targets two stages of the malaria parasite.
    Would it benefit from language editing? No
    Would you recommend this preprint to others? Yes, but it needs to be improved
    Is it ready for attention from an editor, publisher or broader audience? Yes, after minor changes

    Competing interests

    The authors declare that they have no competing interests.

  3. PREreview

    This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/14159663.

    Does the introduction explain the objective of the research presented in the preprint? Yes The introduction clearly states the objective of assessing the safety and efficacy of the RH5.1/Matrix-M blood-stage malaria vaccine candidate in children aged 5-17 months in Burkina Faso. It provides context on existing pre-erythrocytic vaccines and explains the potential benefits of a blood-stage vaccine.
    Are the methods well-suited for this research? Highly appropriate The study uses a double-blind, randomized, controlled design, which is the gold standard for vaccine efficacy trials. The methods include appropriate control groups, blinding procedures, and statistical analyses. The trial design, including the use of two different dosing regimens, allows for comprehensive evaluation of the vaccine's safety and efficacy.
    Are the conclusions supported by the data? Somewhat supported The conclusions are largely supported by the data presented. The authors accurately report the efficacy results and safety profile. However, some conclusions about the potential for combining this vaccine with pre-erythrocytic vaccines are somewhat speculative and would require further study to confirm these claims. Additionally, longer-term follow-up studies are necessary to confirm the durability and efficacy of the vaccine.
    Are the data presentations, including visualizations, well-suited to represent the data? Somewhat appropriate and clear The current figures and tables effectively communicate the key results, but additional visualizations could further enhance clarity and interpretation. Specifically, adding forest plots for efficacy comparisons between dosing regimens and subgroups would provide a more detailed view of the effect sizes and confidence intervals. Furthermore, the Kaplan-Meier curves for efficacy could benefit from additional annotations or breakpoints, highlighting when and where differences in efficacy become evident between groups. These enhancements would make it easier for readers to grasp the nuances of vaccine performance across different conditions and over time.
    How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Somewhat clearly The authors mention ongoing trials but could improve the discussion by specifying how these studies will address the limitations of the current trial, such as testing in areas with varying malaria transmission intensities. Highlighting potential combination strategies with pre-erythrocytic vaccines in future work could also provide a roadmap for their next experiments.
    Is the preprint likely to advance academic knowledge? Highly likely This study represents the first demonstration of significant efficacy for a blood-stage malaria vaccine in young children. It provides important proof-of-concept data that could lead to new approaches in malaria vaccine development and potentially improve overall vaccine efficacy when combined with existing strategies.
    Would it benefit from language editing? No The preprint is well-written and clear. Any minor language issues do not significantly impact the understanding of the research, however simplifying some of the technical jargon or adding parenthetical explanations for key terms.
    Would you recommend this preprint to others? Yes, it's of high quality This preprint reports on a well-designed and executed clinical trial with important implications for malaria vaccine development. The methods are rigorous, the results are clearly presented, and the discussion provides valuable context and future directions.
    Is it ready for attention from an editor, publisher or broader audience? Yes, as it is The preprint is well-structured, comprehensive, and reports on important findings from a rigorously conducted clinical trial. While the peer review may suggest some minor revisions or additional analyses, the core content and conclusions are likely to remain unchanged and are of immediate interest to the scientific community.

    Competing interests

    The authors declare that they have no competing interests.

  4. Version published to 10.1101/2024.10.15.24315473v1 on medRxiv