Role of malaria exposure and off-target responses on RTS,S/AS02<sub>A</sub> vaccine immunogenicity and protection in Mozambican children.

Including Manhiça children only, higher levels of IgG to PfBSag showing an off-target profile were associated with a reduced hazard of having a first or only clinical malaria episode, with statistical significance for PfMSP5 (HR 0.81, 95% CI 0.69–0.96, p = 0.013) and PfMSP1 Bl2 (HR 0.75, 95% CI 0.58–0.96, p = 0.024), and borderline significance for PfRh4.2 (HR 0.80, 95% CI 0.63–1.01, p = 0.064) and PfRh5 (HR 0.77, 95% CI 0.58–1.01, p = 0.060).

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A trend of higher IgG levels to PfRh5 was also observed, although this difference did not reach statistical significance (1.57, 95% CI 1.1–2.25, p = 0.089) (Fig. 3 ).

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Adjusting by site and M3 CSP IgG levels (Table 3 ), significant associations were maintained for IgG levels to PfMSP5 and PfMSP1 Bl2 and borderline significant for IgG levels to PfRh5, PfRh4.2 and PfEBA140.

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