Browsing by Author "Ampomah, P."
Now showing 1 - 4 of 4
Results Per Page
Sort Options
Item Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination(NATURE COMMUNICATIONS, 2021) Larsen, M.D.; Lopez-Perez, M.; Dickson, E.K.; Ampomah, P.; Ederveen, H.; Koeleman, C.A.M.; Nouta, J.; Ndam, T.; Mordmüller, B.; Salanti, A.; Nielsen, M.A.; Massougbodji, A.; Schoot, C.E.; Ofori, M.F.; Wuhrer, M.; Hviid, L.; Vidarsson, G.Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family members mediate receptor- and tissue-specific sequestration of infected erythrocytes (IEs) in malaria. Antibody responses are a central component of naturally acquired malaria immunity. PfEMP1-specific IgG likely protects by inhibiting IE sequestration and through IgG-Fc Receptor (FcγR) mediated phagocytosis and killing of antibody-opsonized IEs. The affinity of afucosylated IgG to FcγRIIIa is up to 40-fold higher than fucosylated IgG, resulting in enhanced antibodydependent cellular cytotoxicity. Most IgG in plasma is fully fucosylated, but afucosylated IgG is elicited in response to enveloped viruses and to paternal alloantigens during pregnancy. Here we show that naturally acquired PfEMP1-specific IgG is strongly afucosylated in a stable and exposure-dependent manner, and efficiently induces FcγRIIIa-dependent natural killer (NK) cell degranulation. In contrast, immunization with a subunit PfEMP1 (VAR2CSA) vaccine results in fully fucosylated specific IgG. These results have implications for understanding protective natural- and vaccine-induced immunity to malaria.Item B-cell responses to pregnancy-restricted and -unrestricted Plasmodium falciparum erythrocyte membrane protein 1 antigens in Ghanaian women naturally exposed to malaria parasites(Infection and Immunity, 2014) Ampomah, P.; Stevenson, L.; Ofori, M.F.; Barfod, L.; Hviid, L.Protective immunity to Plasmodium falciparum malaria acquired after natural exposure is largely antibody mediated. IgG-specific P. falciparum EMP1 (PfEMP1) proteins on the infected erythrocyte surface are particularly important. The transient antibody responses and the slowly acquired protective immunity probably reflect the clonal antigenic variation and allelic polymorphism of PfEMP1. However, it is likely that other immune-evasive mechanisms are also involved, such as interference with formation and maintenance of immunological memory. We measured PfEMP1-specific antibody levels by enzyme-linked immunosorbent assay (ELISA) and memory B-cell frequencies by enzyme-linked immunosorbent spot (ELISPOT) assay in a cohort of P. falciparum-exposed nonpregnant Ghanaian women. The antigens used were a VAR2CSA-type PfEMP1 (IT4VAR04) with expression restricted to parasites infecting the placenta, as well as two commonly recognized PfEMP1 proteins (HB3VAR06 and IT4VAR60) implicated in rosetting and not pregnancy restricted. This enabled, for the first time, a direct comparison in the same individuals of immune responses specific for a clinically important parasite antigen expressed only during well-defined periods (pregnancy) to responses specific for comparable antigens expressed independent of pregnancy. Our data indicate that PfEMP1- specific B-cell memory is adequately acquired even when antigen exposure is infrequent (e.g., VAR2CSA-type PfEMP1). Furthermore, immunological memory specific for VAR2CSA-type PfEMP1 can be maintained for many years without antigen reexposure and after circulating antigen-specific IgG has disappeared. The study provides evidence that natural exposure to P. falciparum leads to formation of durable B-cell immunity to clinically important PfEMP1 antigens. This has encouraging implications for current efforts to develop PfEMP1-based vaccines. © 2014, American Society for Microbiology.Item Effect of Asymptomatic Plasmodium falciparum Parasitaemia on Platelets Thrombogenicity in Blood Donors(Indian Journal of Hematology and Blood Transfusion, 2021) Aninagyei, E.; Adu, P.; Rufai, T.; Ampomah, P.; Kwakye-Nuako, G.; Egyir-Yawson, A.; Acheampong, D.O.Currently, blood donors in Ghana are not screened for malaria parasites. Therefore, this study assessed platelet thrombogenicity in blood donors infected asymptomatically with Plasmodium falciparum and the relationship between tumour necrosis factor alpha (TNFa), 8-iso-prostaglandin F2a oxidative stress biomarker (8- iso-PG2a), C-reactive protein (hs-CRP) and D-dimer, and platelet thrombogenes levels. Haematology analyser was used to enumerate platelet count and platelet indices in 80 P. falciparum infected blood donors and 160 matched noninfected controls. Replicate serum levels of von Willebrand Factor (vWF), platelet factor 4 (PF4), P-selectin thrombogenic factors as well as TNF-a and 8-iso-PG2a were determined using enzyme immuno-assay while high sensitive hs-CRP and D-dimer concentrations were determined by fluorescent immunoassay. The geometric mean of parasite density in malaria infected donors was 1784 parasites/ lL (505-2478 parasites/lL). This led to significant increase in the mean levels of 8-iso-PG2a, hs-CRP, TNF-a and D-dimer. However, PF4, P-selectin were significantly lower in infected donors while vWF levels did not differ significantly among the groups even though lower levels were observed in the infected donors. Significant direct relationship existed between both P-selectin and PF4 and platelet count, and plateletcrit and platelet large cell ratio whereas these thrombogenic factors varied inversely to 8-iso-PG2a, TNF-a and hs-CRP. Relative thrombocytopaenia was associated with significant reduction in P-selectin and platelet factor 4 levels together with increased 8-iso-PG2a, hs-CRP, TNF-a and D-dimer levels. Taken together, it is recommended that all P. falciparum infected blood donors should be deferred.Item Kinetics of B cell responses to plasmodium falciparum erythrocyte membrane protein 1 in ghanaian women naturally exposed to malaria parasites(Journal of Immunology, 2014-06) Ampomah, P.; Stevenson, L.; Ofori, M.F.; Hviid, L.Naturally acquired protective immunity to Plasmodium falciparum malaria takes years to develop. It relies mainly on Abs, particularly IgG specific for Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins on the infected erythrocyte surface. It is only partially understood why acquisition of clinical protection takes years to develop, but it probably involves a range of immune-evasive parasite features, not least of which are PfEMP1 polymorphism and clonal variation. Parasite-induced subversion of immunological memory and expansion of “atypical” memory B cells may also contribute. In this first, to our knowledge, longitudinal study of its kind, we measured B cell subset composition, as well as PfEMP1-specific Ab levels and memory B cell frequencies, in Ghanaian women followed from early pregnancy up to 1 y after delivery. Cell phenotypes and Ag-specific B cell function were assessed three times during and after pregnancy. Levels of IgG specific for pregnancy-restricted, VAR2CSA-type PfEMP1 increased markedly during pregnancy and declined after delivery, whereas IgG levels specific for two PfEMP1 proteins not restricted to pregnancy did not. Changes in VAR2CSA-specific memory B cell frequencies showed typical primary memory induction among primigravidae and recall expansion among multigravidae, followed by contraction postpartum in all. No systematic changes in the frequencies of memory B cells specific for the two other PfEMP1 proteins were identified. The B cell subset analysis confirmed earlier reports of high atypical memory B cell frequencies among residents of P. falciparum–endemic areas, and indicated an additional effect of pregnancy. Our study provides new knowledge regarding immunity to P. falciparum malaria and underpins efforts to develop PfEMP1-based vaccines against this disease.