Figure 3.

Model of PfRh2b-dependent and -independent inhibitory immune responses. Examples of immune neutralization that is either PfRh2b allele-specific or allele transcendent is illustrated using individual samples from Senegal (A) and all samples from Tanzania, Senegal, and Mali (B). A significant difference is considered greater than 15% difference in inhibition, the degree of difference tolerated in replicates of the same strain in the GIA. A, Situation A shows no significant difference in immune inhibition between the 3 transgenic strains, whether low inhibition or high inhibition, termed allele-independent immunity. Situations B–F demonstrate differences in inhibition specifically due to the allelic form of PfRh2b (allele-specific immunity). Situation B shows increased inhibition of DEL relative to the WT and KO. Such a result could indicate that the deletion in the protein is revealing an alternative epitope of PfRh2b. In situation C, there is an “immune escape” phenotype observed for both the PfRh2b deletion as well as the KO, implying that the differences in inhibition observed are specifically due to the allele of PfRh2b present. Situation D shows “immune escape” for the PfRh2b KO only. Situation E shows enhanced inhibition of both the WT and the deletion allele, and situation F shows incremental increases in inhibition from WT, to PfRh2b deletion, to PfRh2b KO. B, The fraction of the total for each type of inhibitory situation is shown for each population. The population genetic prevalence of the PfRh2b full-length and PfRh2b deletion alleles are shown below as bars.

Abbreviations: DEL, PfRh2b deletion single crossover parasites; GIA, growth inhibition assay; KO, 3D7∆2b, C2 parasites; PfRh2b, Plasmodium falciparum reticulocyte-binding protein homologue 2b; WT, PfRh2b wild-type replacement parasite line (1A).