Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017160 (gastroenteritis)
 11,398 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibody-secreting cells (ASC) were enumerated in gut- and bronchus-associated lymphoid tissues of pigs exposed to three antigenically related coronaviruses: virulent transmissible gastroenteritis virus (TGEV), attenuated TGEV, and porcine respiratory coronavirus (PRCV). Exposure of 11-day-old pigs to virulent TGEV resulted in severe gastroenteritis and virus shedding mainly in feces but also to a limited extent in nasal secretions. PRCV and attenuated TGEV exposure produced no clinical signs and only one pig given a high dose of attenuated TGEV shed virus in feces, but virus was shed from the nasal passages. Nasal virus titers were highest after PRCV inoculation of pigs. Mononuclear cells were isolated from spleens, mesenteric, and bronchial lymph nodes of pigs and assayed for virus-specific IgG and IgA antibody secretion by an enzyme-linked immunospot assay. Virus-specific ASC peaked at postinoculation days 12 to 24 and IgG-ASC outnumbered IgA-ASC in all tissues tested. The greatest numbers of ASC were in mesenteric lymph nodes of virulent TGEV-exposed pigs and in BLN of PRCV-exposed pigs. Attenuated TGEV induced intermediate ASC responses in the gut and respiratory tract. Secondary in vitro ASC responses to inactivated TGEV or PRCV paralleled the primary responses except in BLN where the numbers of memory ASC were high for both TGEV- and PRCV-exposed pigs. We conclude that: 1) a single exposure of pigs to PRCV either oral-nasally or by aerosol leads to potent systemic and bronchus-associated, but not gut-associated, ASC responses; 2) a high dose of attenuated TGEV (4 x 10(8) plaque-forming units) is more effective than PRCV (6 x 10(5) or 2 x 10(8) plaque-forming units) or a lower dose of attenuated TGEV (7 x 10(6) plaque-forming units) in eliciting gut-associated ASC; 3) although virulent and a high dose of attenuated TGEV induce high numbers of ASC in the tissues tested, virulent TGEV induces the most ASC in the gut and IgA-ASC in all lymphoid tissues; and 4) virus replication in the gut or respiratory tract is a major factor affecting the magnitude of an ASC response at that site and may be necessary for the recruitment of IgG- and IgA-ASC and memory cells in large numbers from other mucosal inductive sites. This unique model of mucosal immunity using antigenically related viruses with distinct tissue tropisms may help to clarify interactions of the various components of the common mucosal immune system.
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PMID:Isotype-specific antibody-secreting cells to transmissible gastroenteritis virus and porcine respiratory coronavirus in gut- and bronchus-associated lymphoid tissues of suckling pigs. 838 4

Alternatives to cell culture systems for production of recombinant proteins could make very safe vaccines at a lower cost. We have used genetically engineered plants for expression of candidate vaccine antigens with the goal of using the edible plant organs for economical delivery of oral vaccines. Transgenic tobacco and potato plants were created that express the capsid protein of Norwalk virus, a calicivirus that causes epidemic acute gastroenteritis in humans. The capsid protein could be extracted from tobacco leaves in the form of 38-nm Norwalk virus-like particles. Recombinant Norwalk virus-like particle (rNV) was previously recovered when the same gene was expressed in recombinant baculovirus-infected insect cells. The capsid protein expressed in tobacco leaves and potato tubers cosedimented in sucrose gradients with insect cell-derived rNV and appeared identical to insect cell-derived rNV on immunoblots of SDS/polyacrylamide gels. The plant-expressed rNV was orally immunogenic in mice. Extracts of tobacco leaf expressing rNV were given to CD1 mice by gavage, and the treated mice developed both serum IgG and secretory IgA specific for rNV. Furthermore, when potato tubers expressing rNV were fed directly to mice, they developed serum IgG specific for rNV. These results indicate the potential usefulness of plants for production and delivery of edible vaccines. This is an appropriate technology for developing countries where vaccines are urgently needed.
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PMID:Expression of Norwalk virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice. 864 75

Based on the tenet of a common mucosal immune system, antigenic stimulation at one mucosal site results in the distribution of antigen-specific IgA precursor cells to distant mucosal sites. However, recent studies suggest that functional compartmentalization and limited reciprocity may exist within some components of the common mucosal immune system. Although oral immunization is often very effective in inducing immunity to respiratory pathogens, the converse (respiratory immunization to prevent enteric diseases) may not be as effective. To address this question and to study interactions between the bronchus-associated (BALT) and gut-associated (GALT) lymphoid tissues related to protective immunity, we used as a model two antigenically related porcine coronaviruses which replicate primarily in the intestine (transmissible gastroenteritis virus, TGEV) or respiratory tract (porcine respiratory coronavirus, PRCV). The tissue distribution and magnitude of the antibody secreting cell (ASC) responses (measured by ELISPOT) and cell-mediated immune responses (measured by lymphoproliferative assays, LPA) coincided with the viral tissue tropisms. Immunization via GALT (gut infection with TGEV) elicited high numbers of IgA ASC and high LPA responses in GALT (gut lamina propria, LP or mesenteric lymph nodes, MLN), but lower responses in BALT (bronchial lymph nodes, BLN) and induced complete protection against enteric TGEV challenge. In contrast immunization via BALT (respiratory infection with PRCV) elicited systemic type responses (high numbers of IgG ASC in the BLN), but few ASC and low LPA responses in the gut LP or MLN and induced only partial protection against enteric TGEV challenge. Thus administration of vaccines intranasally may not be optimally effective for inducing intestinal immunity in contrast to the reported efficacy of oral vaccines for inducing respiratory immunity.
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PMID:Mucosal immunity: an overview and studies of enteric and respiratory coronavirus infections in a swine model of enteric disease. 898 61

Viruses that infect cells in the gastrointestinal tract are well suited for examining the immune response to oral delivery of antigen and for exploring the advantages and pitfalls of oral vaccines. Norwalk virus (NV) (family Caliciviridae, genus Calicivirus) causes acute gastroenteritis in all age groups. The NV capsid is composed of 180 copies of a single 58000 molecular weight protein which spontaneously forms virus-like particles (VLPs) that can be purified in extremely high yields (22 mg per 300 ml culture) when produced using the baculovirus expression system. We are testing the potential of these recombinant NV (rNV) particles for use as an oral vaccine by administering them to mice and volunteers. Mice were orally inoculated four times with rNV particles in concentrations ranging from 5 to 500 micrograms in the absence of adjuvant or from 5 to 200 micrograms with 10 micrograms of cholera toxin. Serum IgG and fecal IgA immune responses were monitored. rNV particles were found to be immunogenic when orally given to mice with or without adjuvant. These particles also were safe and immunogenic when orally given to volunteers. These studies show that rNV particles are an excellent model to test the oral delivery of mucosal immunogens in general, and that rNV particles are ideal candidates for vaccine development in particular.
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PMID:Recombinant Norwalk virus-like particles as an oral vaccine. 901 21

Coeliac disease is diagnosed by means of jejunal biopsy, an invasive procedure. Anti-gliadin antibodies (AGA) have therefore been used in the first screening of the disease. On the other hand, low titers of AGA are widely detected also in normal subjects. In order to investigate if low levels of AGA could be correlated with laboratory and clinical data, we performed a study on 167 subjects with various illnesses, such as recurrent abdominal pain, failure to thrive, short stature, diarrhoea or constipation, cow-milk protein intolerance and/or food allergy, recurrent vomiting or previous gastroenteritis, all non coeliac conditions which have been associated with AGA presence. Seventy coeliac children, all biopsied, were selected as a control group. Among the 167 cases we found 60 subjects positive for AGA (35.9%), a high proportion as compared with the general population. Only 33/167 patients, all IgG and IgA AGA positive, fulfil our laboratory and clinical criteria to perform a 'confirming' biopsy. For the 134 residual cases (14 IgA, 13 only IgG AGA positive, 107 AGA negative) a diagnosis of coeliac disease has been excluded by clinical criteria (scoring). As a whole, the patients with coeliac disease had significantly higher levels of AGA of both IgG and IgA classes (p < 0.01). On the other hand, no significant difference emerged for all the anamnestic and laboratory parameters considered between AGA+ and AGA- non-coeliac subjects. However, laboratory parameters of IgG-AGA and/or IgA-AGA positive patients were similar to those of coeliac children for ion, Xylose, total IgA count. As no biopsied case showed mucosal atrophy, it is suggested that the presence of even low AGA levels in non-coeliac children may represent a highly sensitive index of intestinal alteration causing an increased permeability to macromolecules, but it is very unlikely that one could detect coeliac children by means of Ig-AGA among such illnesses and normal subjects. Strong clinical diagnosis and laboratory parameters are required to justify intestinal biopsies. In fact, the production of AGA seems to be a merely immunological phenomenon linked to an increased and probably transient permeability to macromolecules of the intestinal mucosa.
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PMID:Screening for coeliac disease: the meaning of low titers of anti-gliadin antibodies (AGA) in non-coeliac children. 906 80

Rotavirus is an important cause of gastroenteritis in young children. Locally produced antibodies in the intestinal mucosa are proposed to play an important role in the defence against rotavirus infection, but it is not established whether IgA alone can neutralize rotavirus, nor if IgA antibodies recognize epitopes involved in protective immunity. To evaluate whether human IgA plays a role in virus neutralization, serum IgA was purified from nineteen rotavirus seropositive individuals and examined for its neutralizing capacity by a peroxidase focus reduction test. In all nineteen sera IgA neutralizing antibodies against serotype 3 (rhesus rotavirus) were demonstrated. Purified IgA was further investigated and shown not only to neutralize rotavirus in solution but also to neutralize rotavirus already pre-bound to epithelial cells (MA-104). IgA epitope blocking assays with monoclonal antibodies directed against heterotypic epitopes on VP4 and VP7, revealed that IgA antibodies from 4/16 sera recognized epitopes on VP4, while 5/16 sera recognized a VP7 epitope. When whole sera were investigated for comparison 7 and 9/16 sera recognized epitopes on VP4 and VP7 respectively.
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PMID:Neutralization of rotavirus and recognition of immunologically important epitopes on VP4 and VP7 by human IgA. 926 58

Rotavirus-specific IgA has been correlated with immune protection against rotavirus reinfection and symptomatic disease. Systemic and mucosal antibody responses were determined by an enzyme-linked immunosorbent assay in 11 infants with severe rotavirus gastroenteritis. Geometric mean titers of antirotavirus serum IgG and IgA antibodies were significantly higher during the convalescence of the disease (P < 0.001 vs. acute-phase titers). Rotavirus-specific fecal sIgA antibodies increased 4 times during the convalescence in 9 (81.8%) children (P < 0.001). The serum IgG and IgA antibody and fecal sIgA antibody responses to individual rotavirus polypeptides were characterized by radioimmunoprecipitation assay (RIPA) using Staphylococcus aureus protein A and the lectin jacalin to precipitate IgG- and IgA-immune complexes, respectively. The main IgG response was directed toward the structural viral proteins VP2, VP4, and VP6 and toward the nonstructural protein NSP2. Serum IgA reactivity was detected by RIPA in all serum samples, with major responses to VP2, VP6, and NSP2. Interestingly, fecal sIgA in convalescent samples reacted strongly toward NSP2 and VP6. These data reinforce the antigenic importance of rotaviral proteins other than VP4 and VP7, such as VP2, VP6, and NSP2, as main targets in the immune response to rotavirus.
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PMID:Viral proteins VP2, VP6, and NSP2 are strongly precipitated by serum and fecal antibodies from children with rotavirus symptomatic infection. 970 Jun 34

Mouse immunoglobulin gene fragments encoding the variable modules of the heavy (VH) and light (VL) chains of a transmissible gastroenteritis coronavirus (TGEV) neutralizing monoclonal antibody (MAb) have been cloned and sequenced. The selected MAb recognizes a highly conserved viral epitope and does not lead to the selection of neutralization escape mutants. Chimeric immunoglobulin genes with the variable modules from the murine MAb and constant modules of human gamma 1 and kappa chains were constructed using RT-PCR. These chimeric immunoglobulins were stably or transiently expressed in murine myelomas and COS cells, respectively. The secreted recombinant antibodies had radioimmunoassay (RIA) titers higher than 10(3) and reduced the infectious virus more than 10(4)-fold. Recombinant dimeric IgA showed a 50-fold enhanced neutralization of TGEV relative to a recombinant monomeric IgG1 which contained the identical antigen binding site. Epithelial cell lines stably-transformed with these constructs and expressing either recombinant IgG or IgA TGEV neutralizing antibodies reduced virus production by > 10(5)-fold after infection with homologous virus, although a residual level of virus production (< 10(2) PFU/ml) remained in less than 0.1% of the cells.
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PMID:Interference of coronavirus infection by expression of IgG or IgA virus neutralizing antibodies. 978 43

Protection against coronavirus infections can be provided by the oral administration of virus neutralizing antibodies. To provide lactogenic immunity, eighteen lines of transgenic mice secreting a recombinant IgG1 monoclonal antibody (rIgG1) and ten lines of transgenic mice secreting recombinant IgA monoclonal antibodies (rIgA) neutralizing transmissible gastroenteritis coronavirus (TGEV) into the milk were generated. Genes encoding the light and heavy chains of monoclonal antibody (MAb) 6A.C3 were expressed under the control of regulatory sequences derived from the mouse genomic DNA encoding the whey acidic protein (WAP) and beta-lactoglobulin (BLG), which are highly abundant milk proteins. The MAb 6A.C3 binds to a highly conserved epitope present in coronaviruses of several species. This MAb does not allow the selection of neutralization escaping virus mutants. The antibody was expressed in the milk of transgenic mice with titers of one million as determined by RIA, and neutralized TGEV infectivity by one million fold corresponding to immunoglobulin concentrations of 5 to 6 mg per ml. Matrix attachment regions (MAR) sequences were not essential for rIgG1 transgene expression, but co-microinjection of MAR and antibody genes led to a twenty to ten thousand-fold increase in the antibody titer in 50% of the rIgG1 transgenic animals generated. Co-microinjection of the genomic BLG gene with rIgA light and heavy chain genes led to the generation of transgenic mice carrying the three transgenes. The highest antibody titers were produced by transgenic mice that had integrated the antibody and BLG genes, although the number of transgenic animals generated does not allow a definitive conclusion on the enhancing effect of BLG co-integration. Antibody expression levels were transgene copy number independent and integration site dependent. The generation of transgenic animals producing virus neutralizing antibodies in the milk could be a general approach to provide protection against neonatal infections of the enteric tract.
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PMID:Lactogenic immunity in transgenic mice producing recombinant antibodies neutralizing coronavirus. 978 44

The intraperitoneal inoculation of pigs with baculovirus-expressed transmissible gastroenteritis virus (TGEV) structural proteins (S, N, M) in conjunction with thermolabile Escherichia coli mutant toxin (LT-R192G) in incomplete Freund's adjuvant (IFA) was tested in an attempt to elicit active immunity to TGEV in gut-associated lymphoid tissues (GALT). Four groups of 63 (1-5-week-old) suckling, TGEV-seronegative pigs were used to assess the efficacy of the recombinant protein vaccine (group 3) in comparison with sham (group 1), commercial vaccine (group 2), and virulent TGEV Miller-strain-inoculated pigs (group 4). The TGEV-specific mucosal and systemic immune responses were measured after in vivo and in vitro stimulation with TGEV-antigens. The major T-cell subset distribution was analyzed in vivo and in vitro after stimulation of mononuclear cells with TGEV (from mesenteric lymph nodes of group 3 inoculated with TGEV-recombinant proteins). Induction of active immunity was assessed by challenge of pigs with virulent TGEV at 27 days of age. Baculovirus-expressed TGEV proteins coadministered with LT-R192G in IFA induced mesenteric lymph node immune responses associated with IgA-antibodies to TGEV and partial protection against TGEV-challenge. The high titers of serum IgG- and virus-neutralizing-antibodies to TGEV in group 3 pigs most likely reflected the dose of TGEV S-protein administered. At the day of TGEV-challenge, the in vitro stimulation of mononuclear cells from the mesenteric lymph nodes of group 3 pigs with inactivated TGEV resulted in an increase in double positive (CD4+CD8+), natural killer (CD2+CD4-CD8+dim) and cytotoxic (CD2+CD4-CD8+bright) T-cell phenotypes, accompanied by increased expression of interleukin-2 receptor and a decrease of the null (CD2-CD4-CD8-/SW6+) cell phenotype.
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PMID:Active immunity and T-cell populations in pigs intraperitoneally inoculated with baculovirus-expressed transmissible gastroenteritis virus structural proteins. 1050 62


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