Further Analysis of Correlates of Protection from a Phase 2a Trial of the Falciparum Malaria Vaccines RTS,S/AS01B and RTS,S/AS02A in Malaria‐Naive Adults

To the Editor—In an article recently published in the Journal, Kester et al [1] reported comparative safety, immunogenicity, and efficacy data on the candidate malaria vaccines RTS,S/AS01B and RTS,S/ AS02A. The study showed that RTS,S/ AS01B is more immunogenic and may offer more protection against homologous malaria challenge than RTS,S/AS02A. The authors conducted further exploratory analyses to identify correlates of vaccine- induced immunity and found that protected vaccine recipients had higher antibody titers and higher cellular responses than did unprotected vaccine recipients. In Figure 7 of the article, the authors presented a scatterplot of antibody titers and CD4 cell responses for 73 individuals, using symbols to show outcome. The authors suggested that both antibody and CD4 cell responses may be independently protective against malaria challenge, on the basis of the observation that, in the scatterplot, individuals with both high CD4 cell responses and high antibody titers were more likely to be protected than individuals with only high CD4 cell responses or only high antibody titers. Although we agree that this is the immediate impression given by the graphic representation, we undertook multiple regression analyses to confirm or refute this impression, quantify the size of the effect, and test the statistical significance of the associations.