Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-2 (of 2 Records) |
Query Trace: Rivera-Marrero CA [original query] |
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Identification of antigenic glycans from Schistosoma mansoni using a shotgun egg glycan microarray
Mickum ML , Prasanphanich NS , Song X , Dorabawila N , Mandalasi M , Lasanajak Y , Luyai A , Secor WE , Wilkins PP , Van Die I , Smith DF , Nyame AK , Cummings RD , Rivera-Marrero CA . Infect Immun 2016 84 (5) 1371-1386 Infection of mammals by the parasitic helminth Schistosoma mansoni induces antibodies to glycan antigens in worms and eggs, but the differential nature of the immune response among infected mammals is poorly understood. To better define these responses we used a shotgun glycomics approach, in which N-glycans from schistosome egg glycoproteins were prepared, derivatized, separated, and used to generate an egg shotgun glycan microarray. This array was interrogated with sera from infected mice, rhesus monkeys, humans, and with glycan-binding proteins and antibodies to gather information about the structures of antigenic glycans, which were also analyzed by mass spectrometry. A major glycan antigen targeted by IgG from different infected species is the FLDNF epitope [Fucalpha3GalNAcbeta4(Fucalpha3)GlcNAc-R], which is also recognized by the IgG monoclonal F2D2. The FLDNF antigen is expressed by all life stages of the parasite in mammalian hosts and F2D2 can kill schistosomula in vitro in a complement-dependent manner. Different antisera also recognized other glycan determinants including core beta-xylose and highly fucosylated glycans. Thus, the natural shotgun glycan microarray of schistosome eggs is useful in identifying antigenic glycans and in developing new anti-glycan reagents that may have diagnostic applications and contribute to developing new vaccines against schistosomiasis. |
Differential expression of anti-glycan antibodies in schistosome-infected humans, rhesus monkeys and mice
Luyai AE , Heimburg-Molinaro J , Prasanphanich NS , Mickum ML , Lasanajak Y , Song X , Nyame AK , Wilkins P , Rivera-Marrero CA , Smith DF , Van Die I , Secor WE , Cummings RD . Glycobiology 2014 24 (7) 602-18 Schistosomiasis is a debilitating parasitic disease of humans, endemic in tropical areas, for which no vaccine is available. Evidence points to glycan antigens as being important in immune responses to infection. Here we describe our studies on the comparative humoral immune responses to defined schistosome-type glycan epitopes in Schistosoma mansoni-infected humans, rhesus monkeys and mice. Rhesus anti-glycan responses over the course of infection were screened on a defined glycan microarray comprising semi-synthetic glycopeptides terminating with schistosome-associated or control mammalian-type glycan epitopes, as well as a defined glycan microarray of mammalian-type glycans representing over 400 glycan structures. Infected rhesus monkeys generated a high immunoglobulin G (IgG) antibody response to the core xylose/core alpha3 fucose epitope of N-glycans, which peaked at 8-11 weeks post infection, coinciding with maximal ability to kill schistosomula in vitro. By contrast, infected humans generated low antibody levels to this epitope. At 18 months following praziquantel therapy to eliminate the parasite, antibody levels were negligible. Mice chronically infected with S. mansoni generated high levels of anti-fucosylated LacdiNAc (GalNAcbeta1, 4(Fucalpha1, 3)GlcNAc) IgM antibodies, but lacked a robust response to the core xylose/core alpha3 fucose N-glycan antigens compared with other species studied, and their sera demonstrated an intermediate level of schistosomula killing in vitro. These differential responses to parasite glycan antigens may be related to the ability of rhesus monkeys to self-cure in contrast to the chronic infection seen in humans and mice. Our results validate defined glycan microarrays as a useful technology to evaluate diagnostic and vaccine antigens for schistosomiasis and perhaps other infections. |
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