Table 1.
Parameters describing the biology of P. falciparum infection.
Figure 1.
Estimated time to onset of parasitemia for those individuals that are infected as a function of anti-CSP antibody titre (A) when combined with T cells expressing two or more of TNF-α, IL-2, IFN-γ or CD40L (B), TNF-α+ CD4+ T cells (C), IL-2+ CD4+ T cells (D), IFN-γ+ CD4+ T cells (E), or CD40L+ CD4+ T cells (F). The best estimate is given by the black line and the 95% confidence intervals are shown in grey. The times to onset of parasitemia in the infectivity controls, who didn’t have detectable anti-CSP antibody titres or CSP-specific T cells are clustered on the left at (0, 8–12) (yellow points). The anti-CSP antibody titres or CSP-specific T cells of protected volunteers in whom there was no onset of parasitemia, are shown at the top for comparison (blue points). The model accurately replicates the association between time to onset of parasitemia in those that become infected (shown in gold and red) and anti-CSP antibodies (B), but does not do so for markers of cellular immunity (B–F), suggesting that the delay in parasitemia due to killing of sporozoites is best explained by anti-CSP antibody titres.
Table 2.
Comparison of models where protection from infection and time to onset of parasitemia depend on (i) anti-CSP antibodies and CSP-specific CD4+ T cells; (ii) anti-CSP antibodies only; (iii) CSP-specific CD4+ T cells only; and (iv) vaccination status only.
Figure 2.
Efficacy against infection as a function of anti-CSP antibody titre and CSP-specific CD4+ T cells.
Estimated efficacy against infection as a function of anti-CSP antibody titre and numbers of CSP-specific CD4+ T cells per million obtained from the sporozoite model. The vertical dashed grey lines denote the median and 90% ranges of the observed anti-CSP antibody titres, and the horizontal dashed grey lines denote the median and 90% ranges of observed numbers of CSP-specific CD4+ T cells. The solid black lines denote the isoclines for 30%, 50%, 70%, and 90% vaccine efficacy against infection. The blue and brown points denote the anti-CSP antibody titres and numbers of CSP-specific CD4+ T cells of protected and infected volunteers, respectively.
Table 3.
Comparison of predicted (black) and observed (blue) efficacy against infection for the sporozoite infection model.
Figure 3.
Comparison of efficacy against infection and efficacy per sporozoite.
Estimated efficacy against infection (green) and efficacy per sporozoite (blue) with 95% confidence intervals as a function of anti-CSP antibody titres obtained using the sporozoite model. A histogram of the distribution of anti-CSP antibody titres is shown in grey.
Figure 4.
Distribution of efficacy against infection.
Estimated distribution of efficacy against infection induced by both RTS,S/AS02 and RTS,S/AS01.
Figure 5.
Comparison of efficacy against infection for RTS,S/AS01 and RTS,S/AS02.
Comparison of efficacy against infection as a function of anti-CSP antibody titre in the absence of CSP-specific CD4+ T cells for RTS,S/AS01 (black) and RTS,S/AS02 (pink) based on the sporozoite infection model. The grey and pink shaded regions denote 95% confidence intervals for the estimated efficacy of RTS,S/AS01 and RTS,S/AS02, respectively. The substantial overlap between the two curves indicates that, conditional upon the magnitude of the induced antibody response, RTS,S/AS01 and RTS,S/AS02 have comparable efficacy. That is, the superior efficacy of RTS,S/AS01 over RTS,S/AS02 is estimated here to be due to the greater magnitude of the induced immune response and not some other property of the adjuvant.