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At least 217 records · Page 12Linked to original sources
PubMed2005

Mucosal immunization with a ricin toxin B subunit-rotavirus NSP4 fusion protein stimulates a Th1 lymphocyte response.

The castor-oil plant Ricinus communis A-B dimeric toxin B subunit (RTB) was genetically linked at its N-terminus with a 90 amino acid peptide from simian rotavirus SA-11 non-structural protein NSP4(90) and produced in Escherichia coli BL21 cells. Biologically active recombinant NSP4(90)-RTB fusion protein was shown to bind glycoprotein asialofetuin receptor molecules in an in vitro enzyme-linked immunosorbent assay (ELISA). Oral inoculation of the purified NSP4(90)-RTB ligand-antigen fusion protein delivered the chimeric protein to intestinal epidermal cells for mucosal immunization against rotavirus infection. Mice fed the NSP4(90)-RTB fusion protein generated higher humoral and intestinal antibody titers than mice inoculated with NSP4(90) alone. Titers of serum IgG2a antibodies were significantly higher than IgG1 titers suggesting a dominant Th1 lymphocyte immune response. ELISA measurement of cytokines secreted from splenocyte isolated from immunized mice confirmed NSP4(90)-RTB fusion protein stimulates a strong Th1 cell-mediated immune response. The experimental results demonstrate that the ricin toxin B subunit N-terminus can be used as a site for delivery of virus antigens to the gut associated lymphoid tissues for RTB-mediated immune stimulation of antiviral mucosal immune responses.

Administration, Oral↗
PubMed1998

Is there a mucosal immune system associated with the mammalian oviduct?

The oviduct is a key component of the reproductive system where essential states such as spermatozoa capacitation, fertilization and early embryo development take place. Recently, an additional role for the entire female reproductive tract has emerged with important implications for our understanding and management of reproductive health, namely, its role in mounting local immune responses against microbial pathogens. Most of the evidence about mucosal immune responses in the female reproductive tract is related to the vagina, with less information available for the uterus. The less known segment in this regard is the oviduct, which prompted us to review and summarize the current state of knowledge on the immune system at the level of the mammalian oviduct. A comprehensive search was conducted in Medline and--for the last two years--also in Current Contents. Result demonstrate that the mammalian oviduct is endowed with many of the elements that characterize a mucosal immune system. However, there are gaps in our knowledge that, in addition to important interspecies differences, make it essential to explore further some fundamental questions regarding this system.

Animals↗
PubMed1998

Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge.

Mucosal tissues are major sites of HIV entry and initial infection. Thus, the induction of a mucosal cytotoxic T lymphocyte (CTL) response is an important feature for an effective HIV vaccine. However, little is known about approaches to induce such a protective CTL response in the mucosa. Here for the first time we show that intrarectal immunization with a synthetic, multideterminant HIV peptide plus cholera toxin adjuvant induced long-lasting, antigen-specific CTL memory in both the inductive (Peyer's patch) and effector (lamina propria) mucosal sites, as well as in systemic sites (spleen), whereas systemic immunization induced specific CTL only in the spleen. Cholera toxin adjuvant, while enhancing the response, was not essential. The CTL recognized target cells either pulsed with HIV peptide or expressing endogenous whole envelope glycoprotein of Mr 160,000 (gp160). Exploring the requirements for CTL induction, we show that mucosal CTL responses are both interleukin 12 and interferon-gamma dependent by using antibody-treated and knock-out mice. Finally, to determine whether a mucosal response is actually protective against local mucosal challenge with virus, we show that intrarectal immunization with the synthetic HIV peptide vaccine protected mice against infection via mucosal challenge with a recombinant vaccinia virus expressing HIV-1IIIB gp160. These studies provide an approach to development of an HIV vaccine that induces CTL immunity in the mucosal and systemic immune systems and protects against mucosal infection with a virus expressing HIV-1 gp160.

AIDS Vaccines↗
PubMed2003

Mucosal immunization with helicobacter, CpG DNA, and cholera toxin is protective.

The mucosal delivery of antigens requires an effective adjuvant to induce mucosal immunity. Current mucosal adjuvants include cholera toxin (CT) and Escherichia coli heat-labile toxin. Unmethylated CpG immunostimulatory oligodeoxynucleotides (ODNs) have been proposed as novel mucosal adjuvants. In this study, mice were immunized with sonicated Helicobacter felis with CT and/or CpG ODN adjuvants. All groups receiving either adjuvant singly or in combination developed increased serum anti-H. felis immunoglobulin G (IgG). The addition of either CpG or CT, or both, produced a specific fecal anti-H. felis IgA response, with the highest IgA levels occurring in animals immunized intranasally with sonicated H. felis with CT and CpG. Following H. felis challenge, addition of the adjuvant CpG ODN provided no significant protection, while groups given CT showed a high degree of protection, although not complete. When CpG ODN was combined with CT and the vaccine combination was delivered intranasally, no bacterial colonization was detected by quantitative PCR, providing "sterile immunity" and demonstrating synergy between CpG ODN and CT.

Adjuvants, Immunologic↗
PubMed2004

[Effect of guizhi decoction on CD4+, CD8+ T-lymphocytes and SIgA in mucosal immune system in intestine of mice with Bi syndrome (collagen induced immune arthritis)].

OBJECTIVE: To observe the effect of Guizhi Decoction (GZD) on immunological indexes in intestinal mucosal immune system of mice with Bi syndrome (collagen induced immune arthritis). METHODS: Eighty male DBA mice were randomly divided into 4 groups, the normal group, the model group and the high and low dosage GZD groups. Model of Bi syndrome was induced by collagen type II. CD4+, CD8+ T-lymphocytes and SIgA in mice' small intestine and PP node were labeled by immunohistochemical staining and their number was calculated using imaging analyzer. RESULTS: Compared with the normal group, in the model group, after immunization with collagen type II, numbers of CD4+ and CD8+ T-lymphocytes and SIgA in mice' intestinal mucosal immune system reduced significantly (P < 0.05 or P < 0.01). After treatment with GZD of both high and low dosage, CD4+ T-lymphocytes and SIgA increased significantly, but significant difference only showed in comparison between the high dosage GZD group and the model group (P < 0.05 or P < 0.01). CONCLUSION: GZD could enhance the immune function in intestinal mucosa in mice with Bi syndrome, thus it might induce immune tolerance and immune inhibition.

Adjuvants, Immunologic↗
PubMed2006

Mucosal immunization with surface-displayed severe acute respiratory syndrome coronavirus spike protein on Lactobacillus casei induces neutralizing antibodies in mice.

Induction of mucosal immunity may be important for preventing SARS-CoV infections. For safe and effective delivery of viral antigens to the mucosal immune system, we have developed a novel surface antigen display system for lactic acid bacteria using the poly-gamma-glutamic acid synthetase A protein (PgsA) of Bacillus subtilis as an anchoring matrix. Recombinant fusion proteins comprised of PgsA and the Spike (S) protein segments SA (residues 2 to 114) and SB (residues 264 to 596) were stably expressed in Lactobacillus casei. Surface localization of the fusion protein was verified by cellular fractionation analyses, immunofluorescence microscopy, and flow cytometry. Oral and nasal inoculations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and mucosal IgA, as demonstrated by enzyme-linked immunosorbent assays using S protein peptides. More importantly, these antibodies exhibited potent neutralizing activities against severe acute respiratory syndrome (SARS) pseudoviruses. Orally immunized mice mounted a greater neutralizing-antibody response than those immunized intranasally. Three new neutralizing epitopes were identified on the S protein using a peptide neutralization interference assay (residues 291 to 308, 520 to 529, and 564 to 581). These results indicate that mucosal immunization with recombinant L. casei expressing SARS-associated coronavirus S protein on its surface provides an effective means for eliciting protective immune response against the virus.

Amino Acid Sequence↗
PubMed1996

Major pathways of mucosal immunity and inflammation: cell activation, cytokine production and the role of bacterial factors.

The gastrointestinal mucosal immune system contains a large, complex mixture of cells that play an essential role in host defence against pathogens and in maintaining the normal balance of tolerance and immunity to constituents of the gastrointestinal lumen. Cells are organized in specialized structures: Peyer's patches (which are important in initiating immune responses and in non-organized compartments) and the lamina propria, where specialized, differentiated cells carry out effector functions. Many of the specialized functions of cells in this system depend on the release of cytokines and other mediators. Recent studies have demonstrated the importance of the gastrointestinal flora in modulating the activity of the mucosal immune cells and exacerbating gastrointestinal inflammation. The function of gastrointestinal immune cells and their mediators appear to be altered in inflammatory bowel diseases and offer potential targets for pharmacological intervention.

Animals↗
PubMed1999

Induction of mucosal immune responses by administration of liposome-antigen formulations and interleukin-12.

We examined the effect of interleukin-12 (IL-12) on the induction of mucosal immune responses following intranasal immunization with liposome-antigen formulations. We assessed the immune response to two recombinant glycoproteins (gD and gB) from bovine herpesvirus type 1 (BHV-1). Positively charged liposomes induced significantly higher gD-specific IgA titers than did immunization with antigen alone. This liposome formulation was selected to further assess the ability of IL-12 to influence mucosal immune responses. Intranasal immunization with IL-12 gD-liposome formulations did not alter the induction of mucosal immune responses. However, a significant increase in anti-gD antibody responses was induced in serum after intranasal immunization with IL-12 gD-liposome when compared with animals immunized with gD-liposomes. Mucosal antibody responses induced by a subcutaneous priming followed by an intranasal boost were significantly higher than those induced by two intranasal immunizations with the same IL-12 liposome-gD formulations. Furthermore, this immunization protocol resulted in the induction of high levels of interferon-gamma (IFN-gamma) in the lungs of subcutaneously primed mice. These findings indicate that the immunomodulatory effects of IL-12 influenced immune responses to a vaccine antigen when delivered intranasally and that these responses can be further enhanced by subcutaneous priming.

Administration, Intranasal↗
PubMed2005

Living high-training low altitude training: effects on mucosal immunity.

Secretory immunoglobulin A (sIgA) is the major immunoglobulin of the mucosal immune system. Whereas the suppressive effect of heavy training on mucosal immunity is well documented, little is known regarding the influence of hypoxia exposure on sIgA during altitude training. This investigation examined the impact of an 18-day Living high-training low (LHTL) training camp on sIgA levels in 11 (six females and five males) elite cross-country skiers. Subjects from the control group (n=5) trained and lived at 1,200 m of altitude, whereas, subjects from the LHTL group (n=6) trained at 1,200 m, but lived at a simulated altitude of 2,500, 3,000 and 3,500 m (3x6-day, 11 h day(-1)) in hypoxic rooms. Saliva samples were collected before, after each 6-day phases and 2 weeks thereafter (POST). Salivary sIgA, protein and cortisol were measured. There was a downward trend in sIgA concentrations over the study, which reached significance in LHTL (P<0.01), but not in control (P=0.08). Salivary IgA concentrations were still lower baseline at POST (P<0.05). Protein concentration increased in LHTL (P<0.05) and was negatively correlated with sIgA concentration after the 3,000 and 3,500 m-phase and at POST (P<0.05 all). Cortisol concentrations were unchanged over the study and no relationship was found between cortisol and sIgA. In summary, data were strongly suggestive of a cumulative negative effect of physical exercise and hypoxia on sIgA levels during LHTL training. Two weeks of active recovery did not allow for proper sIgA recovery. The mechanism underlying this depression of sIgA could be mediated by neural factors.

Adult↗
PubMed2003

Induction of antigen-specific systemic and mucosal immune responses by feeding animals transgenic plants expressing the antigen.

A report from that the presence of lactogenic immunity in pigs protected suckling piglets from porcine epidemic diarrhea virus (PEDV) infection suggested that inducing mucosal immune responses in lactating pigs is an effective way of protecting swine from PEDV infection. In this study, we developed transgenic tobacco plants that express the antigen protein corresponding to the neutralizing epitope of PEDV spike protein, and tested whether feeding the plants to pigs induced an effective immune response against PEDV infection. First, we confirmed the immunogenicity of the plant-derived antigen by using a plaque reduction neutralization assay with serum obtained after injecting mice with protein extracted from the transgenic plants. Feeding the transgenic plants to mice induced both systemic and mucosal immune responses against the antigen. The induced antibodies inhibited virus infection in the plaque reduction neutralization assay. These results suggest that feeding animals transgenic plants carrying antigen genes is an effective strategy to induce protective immune responses against PEDV infection.

Administration, Oral↗
PubMed1996

Mucosal immunity: an overview and studies of enteric and respiratory coronavirus infections in a swine model of enteric disease.

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.

Administration, Intranasal↗
PubMed1986

Strong adjuvant properties of cholera toxin on gut mucosal immune responses to orally presented antigens.

There is a great need for substances that can act as adjuvants on local mucosal immune responses to perorally (p.o.) administered immunogens and which could be included in future oral vaccines. In this study we show that in mice cholera toxin (CT) is a potent adjuvant on enteric mucosal immune responses to related (cholera B subunit) as well as unrelated (KLH) antigens presented by the p.o. route. The adjuvant action of CT was dose-dependent and was achieved only when CT was given p.o. and together with the antigen. Both priming (memory induction) and boosting of the gut mucosal immune system by the oral route were greatly potentiated by CT. High numbers of specific antibody-producing cells as well as substantial mucosal memory in the lamina propria were stimulated by p.o. priming immunizations if CT adjuvant was included. Anamnestic responses could be elicited by a single p.o. booster immunization for at least 10 weeks and probably much longer. The adjuvant action of CT is suggested to involve activation of adenylate cyclase and cyclic AMP-mediated signals with differential effects on B and regulatory T intestinal lymphocytes. The adjuvant-active dose of CT, 100-500 ng, was lower than the immunogenic dose (2 micrograms) and much below the p.o. dose needed for detectable net fluid secretion in mouse intestine (5-10 micrograms). Cholera B subunit (10 micrograms) administered p.o. together with 500 ng of CT was 50 times more effective in stimulating gut mucosal anti-toxin responses compared with B subunit vaccine alone. Our results suggest that CT or substances that use similar adjuvant mechanisms may substantially increase the mucosal immunogenicity and efficacy of non-replicating oral vaccines.

Adenylyl Cyclases↗
PubMed2001

Induction of systemic and mucosal immune response in cattle by intranasal administration of pig serum albumin in alginate microparticles.

Biodegradable microparticles are an efficient mucosal delivery system that protect antigens from the harsh mucosal environment and facilitate their uptake by M cells at the epithelium of mucosal-associated lymphoid tissue. In this study, we determined the systemic and mucosal immune response in calves following intranasal and oral immunization with pig serum albumin (PSA) encapsulated in alginate microparticles. The size of the particles ranged from 1 to 50 microm in diameter, with 95% of the particles being smaller than 5 microm. High levels of anti-PSA IgG1 antibodies were found in the serum, nasal secretions, and to a less extent in saliva of calves vaccinated intranasally, but not orally, with PSA-microparticles. There was no significant increase of PSA-specific IgA. A weak lymphocyte proliferative immune response was observed in peripheral blood mononuclear cells (PBMCs), and few anti-PSA antibody-secreting cells (ASC) were detected in the blood of calves immunized intranasally. The combined systemic and mucosal response observed in intranasally immunized animals may be attributed to the wide variation in the size of the alginate microparticles, with smaller particles translocating to regional lymph nodes and inducing a systemic immune response, and larger particles being retained in the NALT and inducing a mucosal immune response. The procedure presented here may be useful as an intranasal vaccine against respiratory diseases in cattle.

Administration, Intranasal↗
PubMed1997

B cell-independent selection of memory T cells after mucosal immunization with Candida albicans.

B cell-deficient mice have normal T cell responses to Ags inoculated systemically; however, it is not known whether they can mount systemic and mucosal T cell responses to Ags through normally B cell-enriched gastrointestinal mucosae. Mucosal colonization of germfree, B cell-deficient J(H)D mice with the pathogenic gastrointestinal fungus, Candida albicans selected splenic CD4+ and CD8+ TCR alphabeta memory T cells, as indicated by 1) increased numbers of splenic CD4+ and CD8+ TCR alphabeta expressing T cells of the CD45RB(low) CD44(high) phenotype, 2) early expansion followed by progressive decrease in the number of splenic CD4+ and CD8+ TCR alphabeta T cells, and 3) concomitant increases in the percentage of apoptosis and proliferation in the latter subsets. Although i.v. challenge of germfree or conventional J(H)D mice with C. albicans did not increase apoptosis or induce changes in the number of splenic memory T cells, i.v. challenge of mucosally immunized germfree J(H)D mice led to further proliferation and expansion of activated splenic CD4+ and CD8+ TCR alphabeta thymic-educated memory T cells, which were first evoked by mucosal immunization. Oral colonization with C. albicans also increased the number of gammadelta and thymic and extrathymic alphabeta T cells in gastrointestinal mucosae. In conclusion, our results are the first strong evidence that thymic and extrathymic T cells participate in mucosal immunity to C. albicans in the absence of B cells; however, CD4+ and thymic-educated CD8+ TCR alphabeta memory subsets evoked by mucosal, but not parenteral (i.v.), challenge contribute to protective immunity to systemic candidiasis.

Animals↗
PubMed2001

Mucosal immunization with HIV-1 gag DNA on cationic microparticles prolongs gene expression and enhances local and systemic immunity.

There is an urgent need to develop vaccines against transmission of HIV through the vaginal and rectal mucosa. In the present study we tested the ability of DNA encoding HIV-1 gag adsorbed onto the surface of cationic polylactide co-glycolide microparticles (PLG-DNA) to induce local and systemic gag-specific immunity following mucosal delivery. We found gag-specific cell- and antibody-mediated responses in local as well as systemic lymphoid tissues following intranasal (IN) immunizations with PLG-DNA but not with naked DNA. IN immunizations with PLG-DNA, but not naked DNA, induced prolonged expression of gag protein in local and systemic lymphoid tissues. These data have important implications for DNA vaccine development.

AIDS Vaccines↗
PubMed2004

Maintenance of long-term immunological memory by low avidity IgM-secreting cells in bone marrow after mucosal immunizations with cholera toxin adjuvant.

To understand the mechanisms involved in maintaining long-term immunological memory following mucosal immunizations, we determined the quality of serum hapten-specific immunoglobulins (Ig) and localized Ig-secreting cells (SC) of various isotypes in acute, persistent/resting memory and effector memory phases following oral versus intra-muscular (IM) immunizations. In the acute phase, both oral and IM immunizations induced high avidity Ig. However, in the persistent/resting memory phase, oral immunizations induced low avidity Ig while IM immunizations induced high avidity Ig. Following oral immunizations, in the persistent/resting memory phase, hapten-specific IgM titers in serum and IgM-SC in bone marrow (BM) dominated the immune response, suggesting an important role for IgM in the maintenance of memory.

Adjuvants, Immunologic↗
PubMed2004

Mucosal immune responses to infections in infants with acute life threatening events classified as 'near-miss' sudden infant death syndrome.

This study examined the hypothesis that dysregulation of mucosal immune responses to respiratory infections is a critical event, which could be causal in respiratory arrest of some previously healthy infants. To examine this hypothesis, a prospective study was undertaken of infants presenting to the emergency department of a major teaching hospital with acute life threatening events (ALTE) of unknown cause and classified as "near-miss" SIDS. Salivary immunoglobulin concentrations were measured on admission and again after 14 days. The salivary immunoglobulins were compared with three control groups: infants with a mild upper respiratory tract infection (URTI); bronchiolitis; and healthy age-matched infants. The salivary IgA and IgM concentrations in the ALTE infants at presentation to hospital indicated a significant mucosal immune response had already occurred, with nearly 60% of the IgA concentrations significantly above the population-based reference ranges. The hyper-immune response was most evident in the ALTE infants with pathology evidence of an infection; 87% of these infants had salivary IgA concentrations on average 10 times higher that the age-related median concentration. The most prevalent pathogen identified in the ALTE infants was respiratory syncytial virus (RSV) (64%). RSV was also identified in all subjects with bronchiolitis. Risk factors for SIDS were assessed in each group. The data indicated that the ALTE infants diagnosed as 'near-miss' SIDS were a relatively homogeneous group, and most likely these ALTE infants and SIDS represent associated clinical outcomes. The study identified exposure to cigarette smoke and elevated salivary IgA concentrations as predictors of an ALTE. The study findings support the hypothesis of mucosal immune dysregulation in response to a respiratory infection in some infants with an ALTE. They provide a plausible explanation for certain SIDS risk factors. The underlying patho-physiological mechanism of proinflammatory responses to infections during a critical developmental period might be a critical factor in infants who have life-threatening apnoea or succumb to SIDS. The study raises the possibility of using salivary IgA to test infants who present with mild respiratory infections to identify a substantial number of infants at risk of developing an ALTE or SIDS, thus enabling intervention management to prevent such outcomes.

Apnea↗
PubMed1993

Enhancement of systemic and mucosal immune responses following oral administration of liposomes.

The effects of liposomes on the systemic and mucosal immune response were investigated using bovine serum albumin (BSA) in BALB/c mice. Following three oral administrations of varied formulations at 1-week intervals, serum BSA-specific IgG levels were increased significantly by BSA encapsulated in liposomes and moderately by a mixture of liposomes and BSA. Serum and salivary BSA-specific IgA levels were elevated by BSA-encapsulating liposomes only. Liposomes thus activate not only the systemic immune response but also the mucosal immune response following their oral administration. However, no increase in salivary IgA levels was observed by intraperitoneal or subcutaneous injection of BSA-encapsulating liposomes. The production of IgA is closely related to the oral administration of liposomes encapsulating antigens. Liposomes thus function as carriers of oral vaccines against various infections of the mucosal surface.

Administration, Oral↗