Declining Antibody Affinity Over Time After Human Vaccination With a Plasmodium falciparum Merozoite Vaccine Candidate

Abstract

Maintaining high-affinity antibodies after vaccination may be important for long-lasting immunity to malaria, but data on induction and kinetics of affinity is lacking. In a phase 1 malaria vaccine trial, antibody affinity increased following a second vaccination but declined substantially over 12 months, suggesting poor maintenance of high-affinity antibodies.

Clinical trials registration: Australian New Zealand Clinical Trials Registry ACTRN12607000552482.

Keywords: affinity maintenance; antibody; antibody affinity; malaria; malaria vaccine.

Figure 1.

IgG subclass responses to MSP2. Individuals received two 40-μg doses (n = 10) or three 10-μg doses (n = 7) of the bivalent MSP2 vaccine. Serum samples collected on days 0, 28, 112, and 336 of the study (and day 196 for the 10-μg dose group) were tested for IgG subclasses including IgG1 (A), IgG2 (B), and IgG3 (C). There was no substantial induction of MSP2-specific IgG4 or IgM (Supplementary Figure 1). The group median and IQR are shown (values are OD) and reactivity between paired samples collected at days 0 and 112, and days 112 and 336 were compared using the Wilcoxon signed rank test. D, IgG subclasses to each MSP2 isoform at days 28, 112, and 336 were compared between the vaccine dosing groups using the Kruskal-Wallis test (median and IQR are shown). Abbreviations: IgG, immunoglobulin G; IQR, interquartile range; MSP2, merozoite surface protein 2; OD, optical density.

Figure 2.

Affinity of IgG induced by vaccination. A, Serum samples collected on days 28, 112, and 336 of the study (and day 196 for the 10-μg dose group) were tested for IgG affinity (data shown as 1/k_d values); higher 1/k_d values represent higher affinity. The group median and IQR are shown and reactivity between paired samples collected at days 28 and 112, and days 112 and 336 were compared using the Wilcoxon signed rank test. B, IgG affinity measured to each MSP2 isoform at days 28, 112, and 336 were compared between the vaccine dosing groups using the Kruskal-Wallis test (median and IQR are shown). C and D, Correlations between antibody affinity and magnitude of IgG1, IgG2, and IgG3 to the 3D7 (C) and FC27 (D) isoforms of MSP2, measured at day 112 (peak response). The Spearman correlation coefficient (ρ) and linear line of best fit are shown. Abbreviations: IgG, immunoglobulin G; IQR, interquartile range; k_d, dissociation rate; MSP2, merozoite surface protein 2.