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

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Abstract

Background

The only licensed malaria vaccine, RTS,S/AS01 E , 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/AS01 E regimens 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/AS01 E regimens across both follow-up periods (12 and 20 months). Each RTS,S/AS01 E regimen significantly reduced the number of new infections in the 20-month follow-up period (control mean 4.1 vs. RTS,S/AS01 E mean 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. ( ClinicalTrials.gov number, NCT03276962 )

Article activity feed

  1. Anders Björkman

    Review 2: "Baseline Malaria Infection Status and RTS,S/AS01E Malaria Vaccine Efficacy"

    Reviewers highlighted that the study challenges previous findings by suggesting pre-existing malaria infection enhances immune response, contradicting studies indicating immunosuppressive effects of malaria on vaccine efficacy.

  2. Matthew Laurens

    Review 1: "Baseline Malaria Infection Status and RTS,S/AS01E Malaria Vaccine Efficacy"

    Reviewers highlighted that the study challenges previous findings by suggesting pre-existing malaria infection enhances immune response, contradicting studies indicating immunosuppressive effects of malaria on vaccine efficacy.