Baseline malaria infection status and RTS,S/AS01E malaria vaccine efficacy

  1. Michal Juraska
  2. Angela M. Early
  3. Li Li
  4. Stephen F. Schaffner
  5. Marc Lievens
  6. Akanksha Khorgade
  7. Brian Simpkins
  8. Nima S. Hejazi
  9. David A. Benkeser
  10. Qi Wang
  11. Laina D. Mercer
  12. Samuel Adjei
  13. Tsiri Agbenyega
  14. Scott Anderson
  15. Daniel Ansong
  16. Dennis K. Bii
  17. Patrick B.Y. Buabeng
  18. Sean English
  19. Nicholas Fitzgerald
  20. Jonna Grimsby
  21. Simon K. Kariuki
  22. Kephas Otieno
  23. François Roman
  24. Aaron M. Samuels
  25. Nelli Westercamp
  26. Christian F. Ockenhouse
  27. Opokua Ofori-Anyinam
  28. Cynthia K. Lee
  29. Bronwyn L. MacInnis
  30. Dyann F. Wirth
  31. Peter B. Gilbert
  32. Daniel E. Neafsey
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Abstract

Background

The only licensed malaria vaccine, RTS,S/AS01E, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy (VE).

Methods

1,500 children aged 5–17 months were randomized to receive four different RTS,S/AS01Eregimens or a rabies control vaccine in a phase 2b clinical trial in Ghana and Kenya. We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods in over 36K participant specimens. We performed a post hoc analysis of VE based on malaria infection status at first vaccination and force of infection.

Results

We observed significant and comparable VE (25–43%, 95% CI union 9–53%) against first new infection for all four RTS,S/AS01Eregimens across both follow-up periods (12 and 20 months). Each RTS,S/AS01Eregimen significantly reduced the number of new infections in the 20-month follow-up period (control mean 4.1 vs. RTS,S/AS01Emean 2.6–3.0). VE against first new infection was significantly higher in participants who were malaria-infected (68%; 95% CI, 50 to 80%) versus uninfected (37%; 95% CI, 23 to 48%) at the first vaccination (P=0.0053) and in participants experiencing greater force of infection between dose 1 and 3 (P=0.059).

Conclusions

All tested dosing regimens blocked some infections to a similar degree. Improved VE in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation. (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</ext-link>number,<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT03276962">NCT03276962</ext-link>)

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