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The pspC Gene of Streptococcus pneumoniae Encodes a Polymorphic Protein, PspC, Which Elicits Cross-Reactive Antibodies to PspA and Provides Immunity to Pneumococcal Bacteremia

Brooks-Walter, Alexis; Briles, David E.; Hollingshead, Susan K.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Publicado em /12/1999 EN
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702.352%
PspC is one of three designations for a pneumococcal surface protein whose gene is present in approximately 75% of all Streptococcus pneumoniae strains. Under the name SpsA, the protein has been shown to bind secretory immunoglobulin A (S. Hammerschmidt, S. R. Talay, P. Brandtzaeg, and G. S. Chhatwal, Mol. Microbiol. 25:1113–1124, 1997). Under the name CbpA, the protein has been shown to interact with human epithelial and endothelial cells (C. Rosenow et al., Mol. Microbiol. 25:819–829, 1997). The gene is paralogous to the pspA gene in S. pneumoniae and was thus called pspC (A. Brooks-Walter, R. C. Tart, D. E. Briles, and S. K. Hollingshead, Abstracts of the 97th General Meeting of the American Society for Microbiology 1997). Sequence comparisons of five published and seven new alleles reveal that this gene has a mosaic structure, and modular domains have contributed to gene diversity during evolution. Two major clades exist: clade A alleles are larger and contain an extra module that is shared with many pspA alleles; clade B alleles are smaller and lack this pspA-like domain. All alleles have a proline-rich domain and a choline-binding repeat domain that show 0% divergence from similar domains in the PspA protein. Immunization of a rabbit with a recombinant clade B PspC molecule produced antiserum that cross-reacted with both PspC and PspA from 15 pneumococcal isolates. The cross-reactive antibodies afforded cross-protection in a mouse model system. Mice immunized with PspC were protected against challenge with a strain that expressed PspA but not PspC. The PspA- and PspC-cross-reactive antibodies were directed to the proline-rich domain present in both molecules.

α-GlcNAc-1→2-α-Glc, the Salmonella Homologue of a Conserved Lipopolysaccharide Motif in the Enterobacteriaceae, Elicits Broadly Cross-Reactive Antibodies

Nnalue, Ndubisi Anthony
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/1998 EN
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To define cross-reactive epitopes in Salmonella lipopolysaccharide (LPS), antisera designated anti-S, anti-Ra, and anti-Re were generated against smooth (S), complete-core (Ra), and deep-core mutant (Re) strains, respectively, and characterized immunochemically. The reactivities of anti-Ra and anti-S with rough LPS (rLPS) chemotypes in enzyme-linked immunosorbent assays (ELISA) decreased progressively with increasing truncation of the complete-core oligosaccharide (e.g., Ra > Rb1 >…Re), while that of anti-Re increased (Ra < Rb1 <…Re). Anti-Ra was relatively more reactive with nonhomologous smooth LPS (sLPS) than anti-S, which in turn was more reactive than anti-Re. This order reflected the relative reactivities of these sera with outer-core rLPS but not those with inner-core rLPS, which suggests that the cross-reactivities of all three sera with sLPS were mediated by antibodies which bind outer-core determinants. Anti-Ra, but not anti-S or anti-Re, reacted with molecules substituted by O chains in immunoblots and revealed ladder-like patterns in sLPSs of various serospecificities. Anti-Ra, however, did not react with O-antigen-specific neoglycoconjugates in ELISA, thus demonstrating specificity for core epitopes. Ra and Rb1 but not other Salmonella core chemotypes inhibited the reactivity of anti-Ra with sLPS in ELISA...

Plasmodium falciparum Infection Elicits Both Variant-Specific and Cross-Reactive Antibodies against Variant Surface Antigens

Chattopadhyay, Rana; Sharma, Amit; Srivastava, Vinod K.; Pati, Sudhanshu S.; Sharma, S. K.; Das, Bhabani S.; Chitnis, Chetan E.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2003 EN
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Naturally acquired antibodies to Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1), the variant surface antigens expressed on the surface of infected erythrocytes, are thought to play a role in protection against P. falciparum malaria. Here, we have studied the development of antibodies to PfEMP-1 in adult malaria patients living in Rourkela, India, an area with a low malaria transmission rate, and prevalence of antibodies to PfEMP-1 in residents of San Dulakudar, India, a village in which P. falciparum malaria is hyperendemic. Convalescent-phase sera from adult malaria patients from Rourkela agglutinate homologous P. falciparum isolates as well as some heterologous isolates, suggesting that they develop partially cross-reactive antibodies to PfEMP-1 following infection. Adult sera from San Dulakudar agglutinate diverse P. falciparum isolates, suggesting that they have antibodies with wide recognition of diverse PfEMP-1. Mixed-agglutination assays using pairs of P. falciparum isolates confirm the presence of both variant-specific and partially cross-reactive antibodies in convalescent-phase sera from Rourkela and adult sera from San Dulakudar. Analysis of PfEMP-1 sequences suggests a molecular basis for the observed cross-reactivity.

Antibodies against the two serotypes of vesicular stomatitis virus measured by enzyme-linked immunosorbent assay: immunodominance of serotype-specific determinants and induction of asymmetrically cross-reactive antibodies.

Charan, S; Hengartner, H; Zinkernagel, R M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1987 EN
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716.8896%
The serological relationship between the two vesicular stomatitis virus (VSV) strains Indiana (VSV-Ind) and New Jersey (VSV-NJ) were analyzed by using an enzyme-linked immunosorbent assay (ELISA). Immunoglobulin G responses, defined by their resistance to treatment with 2-mercaptoethanol, were assessed by ELISA by using sucrose gradient-purified VSV or purified VSV glycoproteins (G) as antigens. When low doses (10(6) PFU) of live VSV or 10(8) PFU of UV-inactivated virus were given intraperitoneally (i.p.), only non-cross-reactive antibody responses were observed in a primary immune response. However, when 10(6) PFU of live VSV were injected intravenously (i.v.), cross-reactive antibodies were generated; anti-VSV-NJ antibodies cross-reacted more against VSV-Ind than did anti-VSV-Ind antibodies against VSV-NJ. When 10(8) PFU of live VSV or UV-inactivated VSV mixed with complete Freund adjuvant was given i.p., high levels of cross-reactive antibodies detectable by ELISA were induced in primary and secondary responses. When purified G protein was used instead of purified whole virus in the ELISA, the cross-reactivity was found to be asymmetrical after immunization with live VSV given i.v. but not after i.p. inoculation; anti-VSV-NJ sera bound almost equally well to VSV-Ind G protein...

Human antibodies recognize multiple distinct type-specific and cross-reactive regions of the minor capsid proteins of human papillomavirus types 6 and 11.

Yaegashi, N; Jenison, S A; Batra, M; Galloway, D A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1992 EN
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615.8768%
Human serum samples derived from a case-control study of patients with cervical carcinoma (n = 174) or condyloma acuminatum (n = 25) were tested for the presence of immunoglobulin G antibodies to human papillomavirus type 6 (HPV6) L2 and HPV11 L2 recombinant proteins in a Western immunoblot assay. Thirty-six samples (18%) were positive for HPV6 L2 antibodies alone, 25 (13%) were positive for HPV11 L2 antibodies alone, and 34 (17%) were positive for both HPV6 L2 and HPV11 L2 antibodies. Thirty samples that were positive for both antibodies were tested for the presence of HPV6-HPV11 L2 cross-reactive antibodies. Fifteen (50%) serum samples contained HPV6-HPV11 L2 cross-reactive antibodies, and 15 (50%) contained independent, type-specific HPV6 L2 and HPV11 L2 antibodies. Altogether, 82% of the HPV6 L2 and HPV11 L2 antibody reactivities were type specific and 18% were HPV6-HPV11 cross-reactive. There was no significant difference in the prevalence of antibody reactivities between samples from patients with cervical carcinoma and those with condyloma acuminatum. Deletion mapping identified five HPV6 L2 regions that reacted with HPV6 type-specific antibodies: 6U1 (amino acids [aa] 152 to 173), 6U2 (aa 175 to 191), 6U3 (aa 187 to 199), 6U4 (aa 201 to 217)...

Antibodies That Are Cross-Reactive for Human Immunodeficiency Virus Type 1 Clade A and Clade B V3 Domains Are Common in Patient Sera from Cameroon, but Their Neutralization Activity Is Usually Restricted by Epitope Masking

Krachmarov, Chavdar; Pinter, Abraham; Honnen, William J.; Gorny, Miroslaw K.; Nyambi, Phillipe N.; Zolla-Pazner, Susan; Kayman, Samuel C.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /01/2005 EN
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620.1423%
Sera from human immunodeficiency virus type 1 (HIV-1)-infected North American patients recognized a fusion protein expressing a V3 loop from a clade B primary isolate virus (JR-CSF) but not from a clade A primary isolate virus (92UG037.8), while most sera from Cameroonian patients recognized both fusion proteins. Competition studies of consensus V3 peptides demonstrated that the majority of the cross-reactive Cameroonian sera contained cross-reactive antibodies that reacted strongly with both V3 sequences. V3-specific antibodies purified from all six cross-reactive sera examined had potent neutralizing activity for virus pseudotyped with envelope proteins (Env) from SF162, a neutralization-sensitive clade B primary isolate. For four of these samples, neutralization of SF162 pseudotypes was blocked by both the clade A and clade B V3 fusion proteins, indicating that this activity was mediated by cross-reactive antibodies. In contrast, the V3-reactive antibodies from only one of these six sera had significant neutralizing activity against viruses pseudotyped with Envs from typically resistant clade B (JR-FL) or clade A (92UG037.8) primary isolates. However, the V3-reactive antibodies from these cross-reactive Cameroonian sera did neutralize virus pseudotyped with chimeric Envs containing the 92UG037.8 or JR-FL V3 sequence in Env backbones that did not express V1/V2 domain masking of V3 epitopes. These data indicated that Cameroonian sera frequently contain cross-clade reactive V3-directed antibodies and indicated that the typical inability of such antibodies to neutralize typical...

Infection enhancement of dengue type 2 virus in the U-937 human monocyte cell line by antibodies to flavivirus cross-reactive determinants.

Brandt, W E; McCown, J M; Gentry, M K; Russell, P K
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1982 EN
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614.9705%
Dengue type 2 virus replication was detected in the U-937 human monocyte cell line when the virus inoculum and the culture medium contained flavivirus antibodies diluted beyond their neutralizing titers. This was in marked contrast to yellow fever virus, which replicated very well in the absence of antibodies; however, 10-fold-higher yields of yellow fever virus could be obtained in the presence of flavivirus antibodies. These infection-enhancing antibodies were obtained from either a dengue type 2 human antiserum or reference hyperimmune obtained from either a dengue type 2 human antiserum or reference hyperimmune mouse ascitic fluid. The infection enhancement phenomenon, previously shown to be due to infection of Fc receptor-bearing cells with virus-antibody complexes, was completely blocked by preincubation of the cells with aggregated gamma globulin. The blocking results suggested an Fc receptor-mediated infection of the U-937 cells as well. A panel of monoclonal antibodies, previously characterized as either virus type specific or flavivirus cross-reactive and with mouse immunoglobulin subclasses G1 and G2a in both categories, were tested for their infection enhancement characteristics. A type-specific neutralizing monoclonal antibody preparation that was diluted beyond its neutralization titer did not cause infection enhancement...

Multiple, heart-cross-reactive epitopes of streptococcal M proteins

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/01/1985 EN
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614.5929%
We present evidence that a highly purified pepsin extract of type 5 streptococcal M protein (pep M5) contains at least three epitopes that are cross-reactive with sarcolemmal membrane proteins of human myocardium. The tissue-cross-reactive determinants of pep M5 are also partially shared with pep M6 and pep M19. Three rabbits immunized with a single 300 micrograms dose of pep M5 developed significant levels of heart-cross-reactive antibodies, as determined by indirect immunofluorescence tests. All three sera also contained antibodies that cross-reacted with pep M6 and pep M19. The heart tissue--specific antibodies that were eluted from sarcolemmal membranes opsonized types 5, 6, and 19 streptococci, indicating that they were directed against protective M protein epitopes on the surface of virulent organisms. Immunofluorescence inhibition tests, using purified M proteins as soluble inhibitors of heart-cross-reactive antibodies, revealed the number and M protein serotype distribution of the tissue-cross-reactive epitopes. Immunoblot analyses demonstrated the sarcolemmal membrane proteins containing the various cross-reactive antigenic determinants.

Cross-reactive antibodies between HIV-gp120 and platelet gpIIIa (CD61) in HIV-related immune thrombocytopenic purpura

BETTAIEB, A; OKSENHENDLER, E; DUEDARI, N; BIERLING, P
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /01/1996 EN
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615.11734%
We have previously demonstrated that immune platelet destruction observed in an AIDS-free HIV-infected patient was associated with the presence of a cross-reactive antibody recognizing both HIV-glycoprotein (gp)120 and platelet gpIIIa (CD61). We have now investigated the presence of such antibodies in other HIV-infected patients, together with the molecular structure of the cross-reactive epitope. Platelet gpIIb/IIIa antibodies were characterized in sera from HIV-infected patients with immune thrombocytopenic purpura by means of an ELISA and a radioimmunoprecipitation procedure (RIP). The platelet antibodies were purified and tested for their ability to recognize HIV-gp. We also tried to characterize the antibody target epitope on HIV-gp120 using recombinant gp and synthetic peptides. IgG with anti-gpIIb/IIIa activity were detected, by means of an ELISA with purified gpIIb/IIIa, in 101/138 (73%) sera from HIV-infected patients with immune thrombocytopenic purpura. The platelet antibodies were purified from 23 sera by absorption/elution on purified immobilized platelet gpIIb/IIIa, and recognition of gpIIIa was confirmed in eight cases with a RIP. Furthermore, the presence of a cross-reactive antibody between HIV-gp120 and platelet gpIIIa was demonstrated in 18/18 patients (including the eight with a confirmed gpIIIa antibody) by the ability of the serum HIV-gp160/120 antibodies to bind to purified gpIIb/IIIa. The cross-reactive epitope was shown to be independent of the carbohydrate moieties of gp120...

Identification of the Targets of Cross-Reactive Antibodies Induced by Streptococcus pneumoniae Colonization▿

Roche, Aoife M.; Weiser, Jeffrey N.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
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708.82164%
Much of the efficacy of current pneumococcal conjugate vaccines lies in their ability to decrease carriage of vaccine serotypes in the population. Novel and more-broadly acting vaccines would also need to target carriage in order to be as effective. We have previously shown that model murine carriage of Streptococcus pneumoniae can elicit antibody-dependent immunity and can protect against a virulent heterologous challenge strain. This study set out to identify S. pneumoniae surface antigens that may elicit cross-reactive antibodies following colonization. Western blot analysis using sera from colonized mice identified the previously characterized immunogens pneumococcal surface protein A (PspA), putative proteinase maturation protein A (PpmA), and pneumococcal surface adhesin A (PsaA) as such antigens. Using flow cytometry, PspA was found to be the major target of surface-bound cross-reactive IgG in sera from TIGR4Δcps-colonized mice, with a modest contribution from PpmA and none from PsaA. In human sera, however, only mutants lacking PpmA were shown to have reduced binding of surface IgG compared to wild-type strains, suggesting that prior exposure to S. pneumoniae in humans may induce PpmA antibodies. We also investigated if cross-reactive antibodies induced by these antigens may be cross-protective against carriage. Despite the immunogenicity of PspA...

Immunization with VAR2CSA-DBL5 Recombinant Protein Elicits Broadly Cross-Reactive Antibodies to Placental Plasmodium falciparum-Infected Erythrocytes▿ †

Avril, Marion; Cartwright, Megan M.; Hathaway, Marianne J.; Hommel, Mirja; Elliott, Salenna R.; Williamson, Kathryn; Narum, David L.; Duffy, Patrick E.; Fried, Michal; Beeson, James G.; Smith, Joseph D.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
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693.1155%
Pregnancy-associated malaria is a severe clinical syndrome associated with the sequestration of Plasmodium falciparum-infected erythrocytes in the placenta. Placental binding is mediated by VAR2CSA, a member of the large and diverse P. falciparum erythrocyte membrane 1 (PfEMP1) protein family. To better understand if conserved regions in VAR2CSA can be targeted by antibodies, we immunized rabbits with VAR2CSA-DBL1 and -DBL5 recombinant proteins produced in Pichia pastoris and developed a panel of seven chondroitin sulfate A (CSA)-binding parasites from diverse geographic origins. Overall, no two parasites in the panel expressed the same VAR2CSA sequence. The DBL1 domains averaged 80% amino acid identity (range, 72 to 89%), and the DBL5 domains averaged 86% amino acid identity (range, 83 to 99%), similar to a broader sampling of VAR2CSA sequences from around the world. Whereas antibodies generated against the VAR2CSA-DBL1 recombinant protein had only limited breadth and reacted with three or four parasites in the panel, immunization with DBL5 recombinant proteins elicited broadly cross-reactive antibodies against all or most parasites in the panel, as well as to fresh clinical isolates from pregnant women. These findings demonstrate that the major PfEMP1 variant expressed by placental isolates exposes strain-transcendent epitopes that can be targeted by vaccination and may have application for pregnancy malaria vaccine development.

Low Level of Cross-Reactive Antibodies to Pandemic Influenza (H1N1) 2009 Virus in Humans in Pre-Pandemic Period in Maharashtra, India

Kode, Sadhana S.; Pawar, Shailesh D.; Tandale, Babasaheb V.; Parkhi, Saurabh S.; Barde, Tanaji D.; Mishra, Akhilesh C.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
EN
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712.6455%
In India, the first outbreak of pandemic influenza (H1N1) 2009 (H1N1pdm) was reported from Panchgani, Maharashtra, in June 2009. Studies from several countries have revealed different levels of pre-existing immunity to H1N1pdm 2009 in various age groups. This study was undertaken using age-stratified pre-pandemic human sera to understand baseline cross-reactivity of antibodies against H1N1pdm. Using cut off antibody titers 20 and 40, overall cross-reactivity was 2.1 and 0.9% respectively by microneutralization assay; 1.2% and 0.7% by haemagglutination inhibition assay, respectively. Results showed higher baseline antibodies and cross-reactive antibodies in the 0–19 age group whereas the elderly age group (≥60) showed no cross-reactivity to H1N1pdm. The higher baseline and cross-reactive antibodies in 0–19 years age group could be because of higher positivity to seasonal H1N1 in that age group. Overall, low level of cross-reactive antibodies to H1N1pdm virus were found in humans in pre-pandemic period in Maharashtra, India.

Anti-Trypanosoma cruzi Cross-Reactive Antibodies Detected at High Rate in Non-Exposed Individuals Living in Non-Endemic Regions: Seroprevalence and Association to Other Viral Serologies

Saba, Esber S.; Gueyffier, Lucie; Dichtel-Danjoy, Marie-Laure; Pozzetto, Bruno; Bourlet, Thomas; Gueyffier, François; Mekki, Yahia; Pottel, Hans; Sabino, Ester C.; Vanhems, Philippe; Zrein, Maan A.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 17/09/2013 EN
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722.80195%
Cross-reactive antibodies are characterized by their recognition of antigens that are different from the trigger immunogen. This happens when the similarity between two different antigenic determinants becomes adequate enough to enable a specific binding with such cross-reactive antibodies. In the present manuscript, we report the presence, at an “abnormal” high frequency, of antibodies in blood samples from French human subjects cross-reacting with a synthetic-peptide antigen derived from a Trypanosoma cruzi (T. cruzi) protein sequence. As the vector of T. cruzi is virtually confined to South America, the parasite is unlikely to be the trigger immunogen of the cross-reactive antibodies detected in France. At present, the cross-reactive antibodies are measured by using an in-house ELISA method that employs the T. cruzi -peptide antigen. However, to underline their cross-reactive characteristics, we called these antibodies “Trypanosoma cruzi Cross Reactive Antibodies” or TcCRA. To validate their cross-reactive nature, these antibodies were affinity-purified from plasma of healthy blood donor and were then shown to specifically react with the T. cruzi parasite by immunofluorescence. Seroprevalence of TcCRA was estimated at 45% in serum samples of French blood donors while the same peptide-antigen reacts with about 96% of T. cruzi -infected Brazilian individuals. In addition...

Large Scale Genome Analysis Shows that the Epitopes for Broadly Cross-Reactive Antibodies Are Predominant in the Pandemic 2009 Influenza Virus A H1N1 Strain

Lara-Ramírez, Edgar E.; Segura-Cabrera, Aldo; Salazar, Ma Isabel; Rodríguez-Pérez, Mario A.; Guo, Xianwu
Fonte: MDPI Publicador: MDPI
Tipo: Artigo de Revista Científica
Publicado em 19/11/2013 EN
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690.5336%
The past pandemic strain H1N1 (A (H1N1)pdm09) has now become a common component of current seasonal influenza viruses. It has changed the pre-existing immunity of the human population to succeeding infections. In the present study, a total of 14,210 distinct sequences downloaded from National Center for Biotechnology Information (NCBI) database were used for the analysis. The epitope compositions in A (H1N1)pdm09, classic seasonal strains, swine strains as well as highly virulent avian strain H5N1, identified with the aid of the Immune Epitope DataBase (IEDB), were compared at genomic level. The result showed that A (H1N1) pdm09 contains the 90% of B-cell epitopes for broadly cross-reactive antibodies (EBCA), which is in consonance with the recent reports on the experimental identification of new epitopes or antibodies for this virus and the binding tests with influenza virus protein HA of different subtypes. Our analysis supports that high proportional EBCA depends on the epitope pattern of A (H1N1)pdm09 virus. This study may be helpful for better understanding of A (H1N1)pdm09 and the production of new influenza vaccines.

The Potent and Broadly Neutralizing Human Dengue Virus-Specific Monoclonal Antibody 1C19 Reveals a Unique Cross-Reactive Epitope on the bc Loop of Domain II of the Envelope Protein

Smith, Scott A.; de Alwis, A. Ruklanthi; Kose, Nurgun; Harris, Eva; Ibarra, Kristie D.; Kahle, Kristen M.; Pfaff, Jennifer M.; Xiang, Xiaoxiao; Doranz, Benjamin J.; de Silva, Aravinda M.; Austin, S. Kyle; Sukupolvi-Petty, Soila; Diamond, Michael S.; Crowe
Fonte: American Society of Microbiology Publicador: American Society of Microbiology
Tipo: Artigo de Revista Científica
Publicado em 19/11/2013 EN
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616.04387%
Following natural dengue virus (DENV) infection, humans produce some antibodies that recognize only the serotype of infection (type specific) and others that cross-react with all four serotypes (cross-reactive). Recent studies with human antibodies indicate that type-specific antibodies at high concentrations are often strongly neutralizing in vitro and protective in animal models. In general, cross-reactive antibodies are poorly neutralizing and can enhance the ability of DENV to infect Fc receptor-bearing cells under some conditions. Type-specific antibodies at low concentrations also may enhance infection. There is an urgent need to determine whether there are conserved antigenic sites that can be recognized by cross-reactive potently neutralizing antibodies. Here, we describe the isolation of a large panel of naturally occurring human monoclonal antibodies (MAbs) directed to the DENV domain II fusion loop (FL) envelope protein region from subjects following vaccination or natural infection. Most of the FL-specific antibodies exhibited a conventional phenotype, characterized by low-potency neutralizing function and antibody-dependent enhancing activity. One clone, however, recognized the bc loop of domain II adjacent to the FL and exhibited a unique phenotype of ultrahigh potency...

Pre-Existing Cross-Reactive Antibodies to Avian Influenza H5N1 and 2009 Pandemic H1N1 in US Military Personnel

Pichyangkul, Sathit; Krasaesub, Somporn; Jongkaewwattana, Anan; Thitithanyanont, Arunee; Wiboon-ut, Suwimon; Yongvanitchit, Kosol; Limsalakpetch, Amporn; Kum-Arb, Utaiwan; Mongkolsirichaikul, Duangrat; Khemnu, Nuanpan; Mahanonda, Rangsini; Garcia, Jean-Mi
Fonte: The American Society of Tropical Medicine and Hygiene Publicador: The American Society of Tropical Medicine and Hygiene
Tipo: Artigo de Revista Científica
Publicado em 08/01/2014 EN
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702.8417%
We studied cross-reactive antibodies against avian influenza H5N1 and 2009 pandemic (p) H1N1 in 200 serum samples from US military personnel collected before the H1N1 pandemic. Assays used to measure antibodies against viral proteins involved in protection included a hemagglutination inhibition (HI) assay and a neuraminidase inhibition (NI) assay. Viral neutralization by antibodies against avian influenza H5N1 and 2009 pH1N1 was assessed by influenza (H5) pseudotyped lentiviral particle-based and H1N1 microneutralization assays. Some US military personnel had cross-neutralizing antibodies against H5N1 (14%) and 2009 pH1N1 (16.5%). The odds of having cross-neutralizing antibodies against 2009 pH1N1 were 4.4 times higher in subjects receiving more than five inactivated whole influenza virus vaccinations than those subjects with no record of vaccination. Although unclear if the result of prior vaccination or disease exposure, these pre-existing antibodies may prevent or reduce disease severity.

Streptococcal-vimentin cross-reactive antibodies induce microvascular cardiac endothelial proinflammatory phenotype in rheumatic heart disease

Delunardo, F; Scalzi, V; Capozzi, A; Camerini, S; Misasi, R; Pierdominici, M; Pendolino, M; Crescenzi, M; Sorice, M; Valesini, G; Ortona, E; Alessandri, C
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
EN
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717.349%
Rheumatic heart disease (RHD) is characterized by the presence of anti-streptococcal group A antibodies and anti-endothelial cell antibodies (AECA). Molecular mimicry between streptococcal antigens and self proteins is a hallmark of the pathogenesis of rheumatic fever. We aimed to identify, in RHD patients, autoantibodies specific to endothelial autoantigens cross-reactive with streptococcal proteins and to evaluate their role in inducing endothelial damage. We used an immunoproteomic approach with endothelial cell-surface membrane proteins in order to identify autoantigens recognized by AECA of 140 RHD patients. Cross-reactivity of purified antibodies with streptococcal proteins was analysed. Homologous peptides recognized by serum cross-reactive antibodies were found through comparing the amino acid sequence of streptococcal antigens with human antigens. To investigate interleukin (IL)-1R-associated kinase (IRAK1) and nuclear factor-κB (NF-κB) activation, we performed a Western blot analysis of whole extracts proteins from unstimulated or stimulated human microvascular cardiac endothelial cells (HMVEC-C). Adhesion molecule expression and release of proinflammatory cytokines and growth factors were studied by multiplex bead based immunoassay kits. We observed anti-vimentin antibodies in sera from 49% RHD AECA-positive patients. Cross-reactivity of purified anti-vimentin antibodies with heat shock protein (HSP)70 and streptopain streptococcal proteins was shown. Comparing the amino acid sequence of streptococcal HSP70 and streptopain with human vimentin...

Dengue Viruses Are Enhanced by Distinct Populations of Serotype Cross-Reactive Antibodies in Human Immune Sera

de Alwis, Ruklanthi; Williams, Katherine L.; Schmid, Michael A.; Lai, Chih-Yun; Patel, Bhumi; Smith, Scott A.; Crowe, James E.; Wang, Wei-Kung; Harris, Eva; de Silva, Aravinda M.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 02/10/2014 EN
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708.7634%
Dengue viruses (DENV) are mosquito-borne flaviviruses of global importance. DENV exist as four serotypes, DENV1-DENV4. Following a primary infection, individuals produce DENV-specific antibodies that bind only to the serotype of infection and other antibodies that cross-react with two or more serotypes. People exposed to a secondary DENV infection with another serotype are at greater risk of developing more severe forms of dengue disease. The increased risk of severe dengue in people experiencing repeat DENV infections appear to be due, at least in part, to the ability of pre-existing serotype cross-reactive antibodies to form virus-antibody complexes that can productively infect Fcγ receptor-bearing target cells. While the theory of antibody-dependent enhancement (ADE) is supported by several human and small animal model studies, the specific viral antigens and epitopes recognized by enhancing human antibodies after natural infections have not been fully defined. We used antibody-depletion techniques to remove DENV-specific antibody sub-populations from primary DENV-immune human sera. The effects of removing specific antibody populations on ADE were tested both in vitro using K562 cells and in vivo using the AG129 mouse model. Removal of serotype cross-reactive antibodies ablated enhancement of heterotypic virus infection in vitro and antibody-enhanced mortality in vivo. Further depletion studies using recombinant viral antigens showed that although the removal of DENV E-specific antibodies using recombinant E (rE) protein resulted in a partial reduction in DENV enhancement...

Trypanosoma-Cruzi Cross-Reactive Antibodies Longitudinal Follow-Up: A Prospective Observational Study in Hematopoietic Stem Cell Transplantation

Saba, Esber S.; Gueyffier, Lucie; Danjoy, Marie-Laure; Vanhems, Philippe; Pozzetto, Bruno; Sobh, Mohamad; Pottel, Hans; Michallet, Mauricette; Zrein, Maan A.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 09/09/2015 EN
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Antibodies named TcCRA “Trypanosoma cruzi Cross Reactive Antibodies” were detected in 47% of blood donors from French population unexposed to the parasite. In order to evaluate the passive or active transmissibility of TcCRA and further characterize its role and etiology, we have conducted a study in a cohort of 47 patients who underwent allogeneic Hematopoietic Stem Cell Transplantations (allo-HSCT). Donors and recipients were tested for TcCRA prior to transplantation. Recipients were further tested during follow-up after transplantation. Demographical, clinical and biological data were collected. Our primary end-point was to assess the risk of TcCRA acquisition after transplantation. During this initial analysis, we observed no seroconversion in patients receiving cells from TcCRA negative donors (n = 23) but detected seroconversion in 4 out of 24 patients who received hematopoietic stem cells from positive donors. Here, we are discussing possible scenarios to explain TcCRA-immune status in recipient after transplantation.

Cross-reactive anti-PfCLAG9 antibodies in the sera of asymptomatic parasite carriers of Plasmodium vivax

Costa,Joana D'Arc Neves; Zanchi,Fernando Berton; Rodrigues,Francisco Lurdevanhe da Silva; Honda,Eduardo Rezende; Katsuragawa,Tony Hiroschi; Pereira,Dhélio Batista; Taborda,Roger Lafontaine Mesquita; Tada,Mauro Shugiro; Ferreira,Ricardo de Godoi Mattos; P
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2013 EN
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The PfCLAG9 has been extensively studied because their immunogenicity. Thereby, the gene product is important for therapeutics interventions and a potential vaccine candidate. Antibodies against synthetic peptides corresponding to selected sequences of the Plasmodium falciparum antigen PfCLAG9 were found in sera of falciparum malaria patients from Rondônia, in the Brazilian Amazon. Much higher antibody titres were found in semi-immune and immune asymptomatic parasite carriers than in subjects suffering clinical infections, corroborating original findings in Papua Guinea. However, sera of Plasmodium vivax patients from the same Amazon area, in particular from asymptomatic vivax parasite carriers, reacted strongly with the same peptides. Bioinformatic analyses revealed regions of similarity between P. falciparum Pfclag9 and the P. vivax ortholog Pvclag7. Indirect fluorescent microscopy analysis showed that antibodies against PfCLAG9 peptides elicited in BALB/c mice react with human red blood cells (RBCs) infected with both P. falciparum and P. vivax parasites. The patterns of reactivity on the surface of the parasitised RBCs are very similar. The present observations support previous findings that PfCLAG9 may be a target of protective immune responses and raises the possibility that the cross reactive antibodies to PvCLAG7 in mixed infections play a role in regulate the fate of Plasmodium mixed infections.