Longevity of Genotype-Specific Immune Responses to Plasmodium falciparum Merozoite Surface Protein 1 in Kenyan Children from Regions of Different Malaria Transmission Intensity

Abstract

Abstract. Naturally acquired immunity to Plasmodium falciparum presents a changing landscape as malaria control programs and vaccine initiatives are implemented. Determining which immunologic indicators remain surrogates of past infection, as opposed to mediators of protection, led us to compare stability of immune responses across regions with divergent malaria transmission intensities. A repeat cross-sectional study of Kenyan children from a malariaholoendemic area and an epidemic-prone area was used to examine longitudinal antibody and interferon-gamma (IFN-γ) responses to the 3D7 and FVO variants of merozoite surface protein 1 (MSP1). Antibodies to MSP1 were common in both study populations and did not significantly wane over a 21-month time period. IFN-γ responses were less frequent and rapidly disappeared in children after a prolonged period of no malaria transmission. Antibody and IFN-γ responses rarely correlated with each other; however, MSP1-specific IFN-γ response correlated with lack of concurrent P. falciparum parasitemia of the same genotype, though only statistically significantly in the malaria-holoendemic region (odds ratio = 0.31, 95% confidence interval = 0.12-0.84). This study affirms that antimalarial antibodies are informative for evaluation of history of malaria exposure within individuals, whereas cell-mediated immunity, though short lived under natural exposure conditions, might provide an assessment of recent infection and protection from parasitemia.

Interaction between maternally derived antibodies and heterogeneity in exposure combined to determine time-to-first Plasmodium falciparum infection in Kenyan infants

“…However, one study also found evidence that even in a region with high malaria infection, the levels of antibody can remain low [27]. Moreover, inherited immunity in the form of cellular responses (as measured by interferon gamma responses to MSP1) in infants living in a low transmission decline rapidly without the presence of malaria infection [28].…”

Immunization with full-length Plasmodium falciparum merozoite surface protein 1 is safe and elicits functional cytophilic antibodies in a randomized first-in-human trial

“…24,25 MSP1 elicits a humoral immune response in natural infections and somebut not allstudies have found a correlation between MSP1 antibody titers and protection from clinical malaria. [26][27][28][29][30] Antibodies against MSP1 can induce multiple effector mechanisms to control blood stage parasitemia, including directly blocking invasion of erythrocytes by merozoites and/or intraerythrocytic development, 23,[31][32][33][34] activation of complement, 35 and opsonization for monocyte-mediated phagocytosis and neutrophil granulocytemediated release of reactive oxygen species (ROS). 36,37 MSP1 can further elicit CD8 + T-cell-mediated cellular immune responses against liver stage parasites.…”

Phenotype and function of IL-10 producing NK cells in individuals with malaria experience

“…Additional studies examining NK cells from children who experience severe disease would be useful to determine if the IL-10-producing NK cell population is lacking in these susceptible individuals. Likewise, samples from individuals that experience high or low Plasmodium exposure would further strengthen the assertion that NK cells playing a regulatory role through production of IL-10 develop following repeated Plasmodium exposure[55]. Previous studies have shown that CD4+ T cells from individuals in malaria endemic areas also display a marked increase in IL-10, which was dependent on malaria infection experience[30].…”