Malaria-exposed individuals have weak B cell responses to RH5 despite repeated infection
(A) IgG binding to RH5 and MSP1 of plasma from individuals living in Kalifabougou, Mali (n = 758 donors). Median fluorescence intensity (MFI) values shown are after division with values for the negative control antigen, CD4. Bars show median values. Dashed lines show average IgG binding of plasma from 42 US donors. The numbers above each group show the percentage of individuals with plasma binding above this negative control average.
(B) Cross-sectional analysis of relationship between plasma IgG binding to RH5 and MSP1 with age. Correlation r and p values were determined using Spearman correlation.
(C) Plasma IgG binding to RH5 of samples from paired acute and convalescent time points. Acute samples were collected upon diagnosis of clinical malaria and convalescent samples were collected ∼1 week after the acute samples. The Wilcoxon sign-rank test was used to analyze changes in binding between the two time points. ∗∗p < 0.01.
(D) RH5-specific IgG levels in plasma of four Malian donors from whom we isolated RH5-specific mAbs over a period of 6 years. The orange bars denote the malaria season, which occurs in the latter half of each year.
(E) Frequency of RH5- or MSP1-positive wells of cultured IgG+ B cells from 30 analyzed donors. Two runs where B cells from different donors were pooled into the same wells were excluded from this analysis. Bars show median values.
(F) Frequency of RH5- or MSP1-positive wells of cultured IgG+ B cells from five pairs of acute and convalescent samples. Two pairs are from the same donor (Kali0346) but were taken from different malaria seasons. For RH5, the five pairs are completely overlapping.
See also Figure S1.