Immunoglobulin G (IgG) responses to Plasmodium falciparum glycosylphosphatidylinositols are short-lived and predominantly of the IgG₃ subclass

The induction of neutralizing immunity to Plasmodium falciparum toxins by vaccination has been proposed as a preventive strategy to limit the severity of malaria. For this approach to be successful, generation of a sustained immune response would be necessary. This study shows that immunoglobulin G (IgG)-subclass responses elicited by the proposed P. falciparum toxin glycosylphosphatidylinositol (GPI) in Papua New Guinean subjects 5-60 years old predominantly involve IgG₃, with a lesser contribution from IgG₁ and an absence of IgG₂ and IgG₄. IgG₃ levels declined sharply within 6 weeks of pharmacological clearance of parasitemia in all subjects, whereas a significant decrease in IgG₁ levels was seen only in subjects ≤19 years old. Because the natural antibody response to P. falciparum GPIs is skewed toward the short-lived IgG₃ subclass, a vaccination strategy with GPI analogues would likely require augmentation by costimulatory molecules, to induce a more persistent anti-GPI response.