Search

Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes. Ab-NK was associated with the successful control of parasitemia after experimental malaria challenge in African adults. In an independent cohort study in children, Ab-NK increased with age, was boosted by concurrent P. falciparum infections, and was associated with a lower risk of clinical episodes of malaria. Nine of the 14 vaccine candidates tested induced Ab-NK, including some less well-characterized antigens: P41, P113, MSP11, RHOPH3, and Pf_11363200. These data highlight an important role of Ab-NK activity in immunity against malaria and provide a potential mechanism for evaluating vaccine candidates. A different antibody angle: Natural killer (NK) cells have been shown to mediate immune responses against Plasmodium falciparum using multiple effector functions. Odera et al. now show that antibody-opsonized P. falciparum merozoites can induce NK cell degranulation and IFN-γ production. This response was not strain specific and reduced invasion of merozoites into uninfected red blood cells. Using a controlled human malaria infection study in adults, they observed that antibody-dependent NK (Ab-NK) cell activity correlated directly with the control of parasitemia. In addition, in a cohort of children living in an endemic malaria setting, Ab-NK frequency increased with age, was boosted during P. falciparum infection, and was linked to a reduced risk of clinical malaria. These findings highlight a key role for antibody-mediated NK cell responses during malaria. —CF [ABSTRACT FROM AUTHOR]

Background: The PfEMP1 family of Plasmodium falciparum antigens play a key role in pathogenesis of severe malaria through their insertion into the surface of parasite infected erythrocytes, and adhesion to host cells. Previous studies have suggested that parasites expressing PfEMP1 subclasses group A and DC8, associated with severe malaria, may have a growth advantage in immunologically naïve individuals. However, this idea has not been tested in longitudinal studies.Methods: Here we assessed expression of the var genes encoding PfEMP1, in parasites sampled from volunteers with varying prior exposure to malaria, following experimental infection by sporozoites (PfSPZ). Using qPCR, we tested for associations between the expression of various var subgroups in surviving parasite populations from each volunteer and 1) the levels of participants' antibodies to infected erythrocytes before challenge infection and 2) the apparent in vivo parasite multiplication rate.Results: We show that 1) expression of var genes encoding for group A and DC8-like PfEMP1 were associated with low levels of antibodies to infected erythrocytes (αIE) before challenge, and 2) expression of a DC8-like CIDRα1.1 domain was associated with higher apparent parasite multiplication rate in a manner that was independent of levels of prior antibodies to infected erythrocytes.Conclusions: This study provides insight into the role of antibodies to infected erythrocytes surface antigens in the development of naturally acquired immunity and may help explain why specific PfEMP1 variants may be associated with severe malaria.Trial Registration: Pan African Clinical Trial Registry: PACTR201211000433272 . Date of registration: 10th October 2012. [ABSTRACT FROM AUTHOR]