Antigenicity and immune correlate assessment of seven Plasmodium falciparum antigens in a longitudinal infant cohort from northern Ghana

Abstract

The current global malaria control and elimination agenda requires development of additional effective disease intervention tools. Discovery and characterization of relevant parasite antigens is important for the development of new diagnostics and transmission monitoring tools and for subunit vaccine development. This study assessed the natural antibody response profile of seven novel Plasmodium falciparum pre-erythrocytic antigens and their potential association with protection against clinical malaria. Antigen-specific antibody levels in plasma collected at six time points from a longitudinal cohort of one-to-five year old children resident in a seasonal malaria transmission area of northern Ghana were assessed by ELISA. Antibody levels were compared between parasite-positive and parasite-negative individuals and the association of antibody levels with malaria risk assessed using a regression model. Plasma antibody levels against five of the seven antigens were significantly higher in parasite-positive children compared to parasite-negative children, especially during low transmission periods. None of the antigen-specific antibodies showed an association with protection against clinical malaria. The study identified five of the seven antigens as markers of exposure to malaria, and these will have relevance for the development of disease diagnostic and monitoring tools. The vaccine potential of these antigens requires further assessment.

Figure 1

Correlation between Hb levels and parasitaemia at the different sampling time points. Correlation coefficient (r) estimates from Spearman correlation tests.

Figure 2

Antigen-specific antibody profiles over the six sampling time points. Boxes represent the median, 25^th and 75^th percentiles and whiskers represent 1.5 times the interquartile range. The median, 25^th and 75^th percentiles, and corresponding P values, have been provided in Supplementary Table 1.

Figure 3

Comparison of antigen-specific antibody levels between parasitemic and non-parasitemic children at the different sampling times. Parasitaemia was determined by microscopic examination of thick and thin blood smears. Boxes represent the median, 25^th and 75^th percentiles and whiskers represent 1.5 times the interquartile range. The median, 25^th and 75^th percentiles, and corresponding P values, have been provided in Supplementary Table 2.

Figure 4

Correlation matrix for pairwise associations between antigen-specific antibody levels. It shows correlation plots in the bottom left part, histograms of antibody titre distribution in the diagonal and the corresponding absolute correlation coefficients and the level of statistical significance (Spearman correlation test) in the upper right part. ^•Statistical significance at P < 0.05; *Significance at P < 0.01; **Significance at P < 0.001; ***Significance at P < 0.0001.

Figure 5

Schematic showing the climatic seasons and sampling time points.