Dominant antibody responses to Fucα1-3GalNAc and Fucα1-2Fucα1-3GlcNAc containing carbohydrate epitopes in Pan troglodytes vaccinated and infected with Schistosoma mansoni

Remoortere, Alexandra van; Vermeer, Henricus J.; Roon, Anne‐Marie M. van; Langermans, Jan A. M.; Thomas, Alan W.; Wilson, R. A.; Die, Irma van; Eijnden, Dirk H. van den; Ágoston, Károly; Kerékgyártó, János; Vliegenthart, Johannes F.G.; Kamerling, Johannis P.; Dam, Govert J. van; Hokke, Cornelis H.; Deelder, André M.

doi:10.1016/j.exppara.2003.12.005

Cited by 45 publications

(35 citation statements)

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“…For S. mansoni, it has been shown previously that multifucosylated GSL glycans remained expressed in later stages of schistosomula development (9) and are surface exposed (28), and they have been shown to be major targets of antibody response in sera of infected individuals (47)(48)(49)51). The reason we did not observe significant binding for lung LN ASC probes might be the differences in the expression of these glycans between S. mansoni and S. japonicum.…”

Section: Discussioncontrasting

confidence: 50%

Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum

et al. 2016

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c Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. We used antibody-secreting cell (ASC) probes to characterize local antiglycan antibody responses against migrating Schistosoma japonicum schistosomula in different tissues of rats. Analysis by shotgun Schistosoma glycan microarray resulted in the identification of antiglycan antibody response patterns that reflected the migratory pathway of schistosomula. Antibodies raised by skin lymph node (LN) ASC probes mainly targeted Nglycans with terminal mannose residues, Gal␤1-4GlcNAc (LacNAc) and Gal␤1-4(Fuc␣1-3)GlcNAc (LeX). Also, responses to antigenic and schistosome-specific glycosphingolipid (GSL) glycans containing highly fucosylated GalNAc␤1-4(GlcNAc␤1) n stretches that are believed to be present at the parasite's surface constitutively upon transformation were found. Antibody targets recognized by lung LN ASC probes were mainly N-glycans presenting GalNAc␤1-4GlcNAc (LDN) and GlcNAc motifs. Surprisingly, antibodies against highly antigenic multifucosylated motifs of GSL glycans were not observed in lung LN ASC probes, indicating that these antigens are not expressed in lung stage schistosomula or are not appropriately exposed to induce immune responses locally. The local antiglycan responses observed in this study highlight the stage-and tissue-specific expression of antigenic parasite glycans and provide insights into glycan targets possibly involved in resistance to S. japonicum infection. Schistosomiasis is one of the neglected tropical diseases with the highest impacts on human health. Over 230 million people are infected worldwide, and over 500 million are at risk of infection (1-3). Infection leads to chronic disease characterized by pronounced immunological reactions against eggs deposited into host tissues by the adult schistosome worms, which eventually lead to fibrosis and organ failure (2). Although effective treatment is available, reinfection occurs rapidly and immunity develops only slowly, stressing the need for a prophylactic vaccine as part of a sustainable control strategy (4-6).Schistosomes have a complex life cycle with different life stages that interact with the human host and that each play a role in immunology, immunopathology, and maintenance of infection. Schistosoma infection occurs after direct contact with water containing the larval form of the parasite (cercariae). Cercariae penetrate the host skin and transform into schistosomula, which enter the vasculature and mature while migrating via the lungs to the portal ve...

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Section: Discussioncontrasting

confidence: 50%

Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum

et al. 2016

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“…For testing the specificity of exoglycosidases used in this study, the synthetic glycoconjugates Fuc␣1-3GalNAc␤1-4GlcNAc␤1-3Gal␣1-(CH 2 ) 5 -squarate (F-LDN-tag) and GalNAc␤1-4(Fuc␣1-3)GlcNAc␤1-3Gal␣1-(CH 2 ) 5 -squarate (LDN-F-tag), recovered following derivatization with diethylsquarate during a protein coupling procedure (25,26) were used.…”

Section: Methodsmentioning

confidence: 99%

Targeted Glycoproteomic Analysis Reveals That Kappa-5 is a Major, Uniquely Glycosylated Component of Schistosoma mansoni Egg Antigens

Meevissen

Balog

Koeleman

et al. 2011

Molecular & Cellular Proteomics

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Glycans present on glycoproteins from the eggs of the parasite Schistosoma mansoni are mediators of various immune responses of the human host, including T-cell modulation and granuloma formation, and they are the target of glycan-specific antibodies. Here we have analyzed the glycosylation of kappa-5, a major glycoprotein antigen from S. mansoni eggs using a targeted approach of lectin purification followed by mass spectrometry of glycopeptides as well as released glycans. We demonstrate that kappa-5 has four fully occupied N-glycosylation sites carrying unique triantennary glycans composed of a difucosylated and xylosylated core region, and immunogenic GalNAc␤1-4GlcNAc (LDN) termini. Furthermore, we show that the kappa-5 specific IgE antibodies in sera of S. mansoni-infected individuals are directed against the core region of the kappa-5 glycans. Whereas two previously analyzed immunomodulatory egg glycoproteins, IPSE/alpha-1 and omega-1, both express diantennary N-glycans with a difucosylated core and one or two Gal␤1-4(Fuc␣1-3)GlcNAc (Lewis X) antennae, the kappa-5 glycosylation appears unique among the major soluble egg antigens of S. mansoni. The distinct structural and antigenic properties of kappa-5 glycans suggest a specific role for kappa-5 in schistosome egg immunogenicity.

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“…Later studies revealed that antibody levels to LDN-dF and FLDN epitopes were strikingly higher than those against LDN, LDNF, and monomeric Le x in vaccinated or infected chimps and infected human cohorts. Interestingly, the anti-LDN-dF and anti-FLDN antibodies were predominantly IgGs, whereas anti-Le x , anti-LDN, and anti-LDNF were IgMs; however, this was not always consistent in human studies (25,26,41,70). Note that in mice, the acute infection is marked by IgM antibodies to LDNF, LDN, and Le x (24).…”

Section: Discussionmentioning

confidence: 77%

“…The lectin HPA (Helix pomatia agglutinin) was purchased from Sigma-Aldrich. An anti-LDN (IgG, clone Y1H5), an anti-LDNF (IgG, clone L6B8), an anti-Le x (IgM, clone 5F1), two anti-LDN-dF (IgM, clone 290-2D9-A; IgM, clone 290-4A8), and an anti-Man 3 GlcNAc 2 (M3GN2; IgM, clone 100-4G11-A) MAb, as well as an anti-FLNDF antibody (IgG, clone F2D2), were developed as MAbs by the production of hybridomas from spleens of mice that had been infected with S. mansoni by using methods described previously (16,(39)(40)(41)(42). The anti-horseradish peroxidase (HRP) antibody (anti-peroxidase, polyclonal rabbit IgG; P7899) was purchased from Sigma-Aldrich and used to detect core ␣3 fucose and core xylose (CF/CX) determinants (43,44).…”

Section: Methodsmentioning

confidence: 99%

“…4C). We screened with six mouse MAbs derived from schistosome-infected mice, referred to as anti-LDNF (clone L6B8), anti-LDN (clone Y1H5), anti-Le X (clone 5F1), anti-M3GN2 (clone 100-4g11-A), and two anti-LDN-dF (clones 290-2D9-A and 290-4A8) MAbs (34,(39)(40)(41)(42). Anti-LDNF bound fractions F9-4 and F11-4.…”

Section: Preparation Of N-glycans From Schistosoma Mansoni Eggsmentioning

confidence: 99%

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Identification of Antigenic Glycans from Schistosoma mansoni by Using a Shotgun Egg Glycan Microarray

et al. 2016

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f 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, and humans and with glycan-binding proteins and antibodies to gather information about the structures of antigenic glycans, which also were analyzed by mass spectrometry. A major glycan antigen targeted by IgG from different infected species is the FLDNF epitope [Fuc␣3GalNAc␤4(Fuc␣3)GlcNAc-R], which is also recognized by the IgG monoclonal antibody 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 ␤-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. Schistosomiasis is a major health problem in tropical and subtropical areas where it is endemic, with more than 200 million people actively infected and 800 million at risk of contracting the disease (1-3). Current treatment for disease is limited to the drug praziquantel (4), but cases of drug resistance have been reported (5). Decades of research on schistosomiasis vaccines have yielded only two candidates for clinical trials, and no encouraging results have been published yet (6-9). Thus, there is an urgent need to develop more sensitive diagnostic methods and to identify new vaccine candidates.Recent studies have shown that a major part of the host immune response to infection is directed against carbohydrate (glycan) antigens in glycoproteins and glycolipids (10-17). A wide variety of unusual antigenic determinants include glycans containing the LDN, fucosylated LDN sequences (LDNF, LDN-dF, FLDN, and FLDNF), Lewis X (Le x ), poly-Le x , core ␣3 fucose, and core ␤2 xylose structures (Fig. 1) (11, 14, 17), many of which are expressed by all developmental stages of schistosomes (18). Interestingly, monoclonal antibodies (MAbs) specific to these glycans recognize these antigens on the surface of 3-h-old schistosomula, and some anti-glycan antibodies can mediate killing in vitro in a complement-dependent fashion (18-21). Schistosoma mansoniinfected rhesus monkeys, which are known to self-cure after infection, have IgG to many glycan antigens, including Le x , LDN, LDNF, core fucose, and core xylose determinants, and their sera are effective in complement-mediated cytolysis of cells expressing Le x as well as schistosomulum larvae in ...

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Dominant antibody responses to Fucα1-3GalNAc and Fucα1-2Fucα1-3GlcNAc containing carbohydrate epitopes in Pan troglodytes vaccinated and infected with Schistosoma mansoni

Cited by 45 publications

References 39 publications

Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum

Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum

Targeted Glycoproteomic Analysis Reveals That Kappa-5 is a Major, Uniquely Glycosylated Component of Schistosoma mansoni Egg Antigens

Identification of Antigenic Glycans from Schistosoma mansoni by Using a Shotgun Egg Glycan Microarray

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