Plasmodium falciparum parasites causing cerebral malaria share variant surface antigens, but are they specific?

Abstract

Variant surface antigens (VSA) expressed on the surface of Plasmodium falciparum-infected red blood cells constitute a key for parasite sequestration and immune evasion. In distinct malaria pathologies, such as placental malaria, specific antibody response against VSA provides protection. This study investigated the antibody response specifically directed against VSA expressed by parasites isolated from individuals presenting a given type of clinical presentation. Plasma and isolates were obtained from four groups of Beninese subjects: healthy adults, patients presenting uncomplicated malaria (UM), cerebral malaria (CM), or pregnancy-associated malaria (PAM). The reactivity of plasma samples from each clinical group was measured by flow cytometry against parasites isolated from individuals from each clinical group. Antibody responses against VSA_UM were predominant in CM, UM and HA plasmas. When analysed according to age in all plasma groups, anti-VSA_CM and -VSA_UM antibody levels were similar until six years of age. In older groups (6-18 and >19 years of age), VSA_UM antibody levels were higher than VSA_CM antibody levels (P = .01, P = .0008, respectively). Mean MFI values, measured in all plasmas groups except the PAM plasmas, remained low for anti-VSA_PAM antibodies and did not vary with age. One month after infection the level of anti-VSA antibodies able to recognize heterologous VSA_CM variants was increased in CM patients. In UM patients, antibody levels directed against heterologous VSA_UM were similar, both during the infection and one month later. In conclusion, this study suggests the existence of serologically distinct VSA_CM and VSA_UM. CM isolates were shown to share common epitopes. Specific antibody response to VSA_UM was predominant, suggesting a relative low diversity of VSA_UM in the study area.