Abstract
BackgroundFormer studies have pointed to a monocyte-dependant effect of antibodies in protection against malaria and thereby to cytophilic antibodies IgG1 and IgG3, which trigger monocyte receptors. Field investigations have further documented that a switch from non-cytophilic to cytophilic classes of antimalarial antibodies was associated with protection. The hypothesis that the non-cytophilic isotype imbalance could be related to concomittant helminthic infections was supported by several interventions and case-control studies.Methods and FindingsWe investigated here the hypothesis that the delayed acquisition of immunity to malaria could be related to a worm-induced Th2 drive on antimalarial immune responses. IgG1 to IgG4 responses against 6 different parasite-derived antigens were analyzed in sera from 203 Senegalese children, half carrying intestinal worms, presenting 421 clinical malaria attacks over 51 months. Results show a significant correlation between the occurrence of malaria attacks, worm carriage (particularly that of hookworms) and a decrease in cytophilic IgG1 and IgG3 responses and an increase in non-cytophilic IgG4 response to the merozoite stage protein 3 (MSP3) vaccine candidate.ConclusionThe results confirm the association with protection of anti-MSP3 cytophilic responses, confirm in one additional setting that worms increase malaria morbidity and show a Th2 worm-driven pattern of anti-malarial immune responses. They document why large anthelminthic mass treatments may be worth being assessed as malaria control policies.
Highlights
Deciphering the interactions between the malaria parasite with the human host and understanding how we acquire immunity to malaria has been fundamental to our malaria vaccine research program
The results confirm the association with protection of anti-merozoite stage protein 3 (MSP3) cytophilic responses, confirm in one additional setting that worms increase malaria morbidity and show a Th2 worm-driven pattern of anti-malarial immune responses
In order to understand the underlying mechanism we compared antibody responses between those protected and those not protected [6]. We found this protection to be associated with a novel immune mechanism we called ‘‘Antibody Dependant Cellular Inhibition (ADCI)’’ in which effective antibodies act in a monocyte (MN)-mediated manner [7]
Summary
Deciphering the interactions between the malaria parasite with the human host and understanding how we acquire immunity to malaria has been fundamental to our malaria vaccine research program. Though this risk decreases, they remain susceptible to malaria attacks until they reach the ages of 15–20 years [3] By the time they are young adults, those who have survived achieve a remarkable state of premunition where they are able to control parasite growth below the threshold at which clinical symptoms occur [4]. They have acquired immunity, but at remarkably low speed. The hypothesis that the non-cytophilic isotype imbalance could be related to concomittant helminthic infections was supported by several interventions and case-control studies
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