Oral MucoRice expressing double-mutant cholera toxin A and B subunits induces toxin-specific neutralising immunity.

Rice-expressed cholera toxin B (CTB) subunit is a cold-chain-free oral vaccine that effectively induces enterotoxin-neutralising immunity. We created another rice-based vaccine, MucoRice, expressing nontoxic double-mutant cholera toxin (dmCT) with CTA and CTB subunits. Western-blot analysis suggested that MucoRice-dmCT had the shape of a multicomponent vaccine.

Mucosal vaccines: novel advances in technology and delivery.

Mucosal vaccines are considered the most suitable type of vaccines to combat emerging and re-emerging infectious diseases because of their ability to induce both mucosal and systemic immunity. Considerable advances have been made toward the development of mucosal vaccines against influenza virus and rotavirus. Many additional mucosal vaccines are in development, including vaccines against cholera, typhoid, traveler's diarrhea and respiratory infections.

Mucosal immunosenescence: new developments and vaccines to control infectious diseases.

Infection of the aero-digestive tract represents a major disease burden of the elderly, and despite recent advances in our understanding of the mucosal immune system, its immunosenescence remains poorly defined. Age-associated alterations of the intestinal and respiratory immune systems occur at distinct times and in a distinct manner. A reduction in gut-associated lymphoreticular tissues, intestinal antigen-specific IgA antibody responses and lack of oral tolerance induction are all associated with aging.

New horizon of mucosal immunity and vaccines.

Progress in the past quarter-century on understanding the molecular, cellular, and in vivo components of the mucosal immune system have allowed us to develop a practical strategy for a novel mucosal vaccine. The mucosal immune system can induce secretory IgA (SIgA) and serum IgG responses to provide two layers of defense against mucosal pathogens. For SIgA-mediated immunity in the gastrointestinal tract, the gut-associated lymphoid tissue contains both the tissue-dependent and tissue-independent IgA components.

Suppression of allergic diarrhea in murine ovalbumin-induced allergic diarrhea model by PG102, a water-soluble extract prepared from Actinidia arguta.

Background: Allergic reactions to food can involve diarrhea, vomiting, nausea and abnormal pain. PG102 has previously been shown to control various factors involved in allergy pathogenesis, including IgE and various Th1 and Th2 cytokines, in vivo as well as in vitro [Park EJ, et al.: J Allergy Clin Immunol 2005;116:1151-1157; Park EJ, et al.

Expression of newly identified secretory CEACAM1(a) isoforms in the intestinal epithelium.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates intestinal immunological homeostasis. However, precise expression patterns of CEACAM1 isoforms remain poorly understood in the intestinal epithelia. Focusing on the small intestinal epithelium of BALB/c mice, we identified three novel splice variants encoding CEACAM1(a)-2, -2C1, and -4C1 by RT-PCR.

Oral immunization: an update.

Purpose Of Review: Oral immunization with vaccines against intestinal infectious diseases has been extensively explored for several decades. Despite the immunologic and economic rationale behind oral immunization, only a few mucosal vaccines are available for the prevention of mucosal infections. Here, we summarize the current status of such vaccines, with a focus on intestinal infectious diseases, describe alternative approaches, and analyze advantages and difficulties encountered with a broad implementation of these vaccines.

Terminology: nomenclature of mucosa-associated lymphoid tissue.

Stimulation of mucosal immunity has great potential in vaccinology and immunotherapy. However, the mucosal immune system is more complex than the systemic counterpart, both in terms of anatomy (inductive and effector tissues) and effectors (cells and molecules). Therefore, immunologists entering this field need a precise terminology as a crucial means of communication.

[MucoRice: development of rice-based oral vaccine].

Parenteral vaccines are used commonly against most of infectious diseases. It is noted that these injection type vaccines are meant to induce protective immunity in the systemic compartment but not aimed at use of the benefits of mucosal immunity as a first line of defense against mucosal infectious diseases such as AIDS, SARS and Influenza. In addition, one of major practical obstacles to current vaccination is storage of the vaccine under refrigeration (or cold-chain) in the developing countries.

Immunological commonalities and distinctions between airway and digestive immunity.

Airway and digestive tissues are the frontlines of the body's defense, being continuously exposed to the outside environment and encountering large numbers of antigens and microorganisms. To achieve immunosurveillance and immunological homeostasis in the harsh environments of the mucosal surfaces, the mucosal immune system tightly regulates a state of opposing but harmonized immune activation and quiescence. Recently, accumulating evidence has revealed that although the respiratory and intestinal immune systems share common mucosa-associated immunological features that are different from those of the systemic immune system, they also show distinctive immunological phenotypes, functions, and developmental pathways.

Enhanced survival of shrimp, Penaeus (Marsupenaeus) japonicus from white spot syndrome disease after oral administration of recombinant VP28 expressed in Brevibacillus brevis.

White spot syndrome virus (WSSV) disease is a major threat to shrimp culture worldwide. Here, we assessed the efficacy of the oral administration of purified recombinant VP28, an envelope protein of WSSV, expressed in a Gram-positive bacterium, Brevibacillus brevis, in providing protection in shrimp, Penaeus japonicus, upon challenge with WSSV. Juvenile shrimp (2-3g in body weight) fed with pellets containing purified recombinant VP28 (50microg/shrimp) for 2 weeks showed significantly higher survival rates than control groups when challenged with the virus at 3 days after the last day of feeding.

Comprehensive gene expression profiling of Peyer's patch M cells, villous M-like cells, and intestinal epithelial cells.

Separate populations of M cells have been detected in the follicle-associated epithelium of Peyer's patches (PPs) and the villous epithelium of the small intestine, but the traits shared by or distinguishing the two populations have not been characterized. Our separate study has demonstrated that a potent mucosal modulator cholera toxin (CT) can induce lectin Ulex europaeus agglutinin-1 and our newly developed M cell-specific mAb NKM 16-2-4-positive M-like cells in the duodenal villous epithelium. In this study, we determined the gene expression of PP M cells, CT-induced villous M-like cells, and intestinal epithelial cells isolated by a novel approach using FACS.

Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5.

The intestinal cell types responsible for defense against pathogenic organisms remain incompletely characterized. Here we identify a subset of CD11c(hi)CD11b(hi) lamina propria dendritic cells (LPDCs) that expressed Toll-like receptor 5 (TLR5) in the small intestine. When stimulated by the TLR5 ligand flagellin, TLR5(+) LPDCs induced the differentiation of naive B cells into immunoglobulin A-producing plasma cells by a mechanism independent of gut-associated lymphoid tissue.

A soluble nonglycosylated recombinant infectious hematopoietic necrosis virus (IHNV) G-protein induces IFNs in rainbow trout (Oncorhynchus mykiss).

Viral glycoproteins interact with cell-surface receptors to mediate virus entry and innate immune system activation. We found that a soluble recombinant infectious hematopoietic necrosis virus G-protein (rIHNV-G) stimulated an early innate immune response mediated by proinflammatory cytokines, IFN1 and IFN-gamma in rainbow trout (Oncorhynchus mykiss) fry. Expression of both IFN1 and IFN-gamma mRNA transcripts was an early event and was rIHNV-G dose-dependent.

Tonic B cell activation by Radioprotective105/MD-1 promotes disease progression in MRL/lpr mice.

Toll-like receptors (TLRs) have a crucial role in sensing microbial products and triggering immune responses. Recent reports have indicated that TLR7 and TLR9 have an important role in activating autoreactive B cells. In addition to TLR7 and TLR9, mouse B cells express TLR2, TLR4 and structurally related Radioprotective105 (RP105).

Innate immunomodulation with recombinant interferon-alpha enhances resistance of rainbow trout (Oncorhynchus mykiss) to infectious hematopoietic necrosis virus.

We examined the in vivo immunostimulatory effects of a recombinant Atlantic salmon (Salmo salar) interferon-alpha2 (rSasaIFN-alpha2). The mature rSasaIFN-alpha2, expressed and purified from Escherichia coli, was administered to rainbow trout (Oncorhynchus mykiss) via the oral, immersion, or intraperitoneal (IP) injection route. Injection of rSasaIFN-alpha2 at 0.

Nasal vaccination with the 40-kilodalton outer membrane protein of Porphyromonas gingivalis and a nontoxic chimeric enterotoxin adjuvant induces long-term protective immunity with reduced levels of immunoglobulin E antibodies.

In this study, we demonstrated that the 40-kDa outer membrane protein of Porphyromonas gingivalis (40-kDa OMP) nasally administered with a nontoxic chimeric adjuvant that combines the A subunit of mutant cholera toxin E112K with the pentameric B subunit of heat-labile enterotoxin from enterotoxigenic Escherichia coli (mCTA/LTB) elicited a long-term protective immune response. Immunization with the 40-kDa OMP and mCTA/LTB induced high levels of 40-kDa-OMP-specific immunoglobulin G (IgG) and IgA antibodies (Abs) in sera and elicited a significant IgA anti-40-kDa OMP Ab response in saliva. These Ab responses were maintained for at least 1 year after the immunization.

Sphingosine 1-phosphate regulates the egress of IgA plasmablasts from Peyer's patches for intestinal IgA responses.

It is well established that Peyer's patches (PPs) are sites for the differentiation of IgA plasma cell precursors, but molecular and cellular mechanisms in their trafficking remain to be elucidated. In this study, we show that alterations in type 1 sphingosine 1-phosphate (S1P) receptor expression during B cell differentiation in the PPs control the emigration of IgA plasma cell precursors. Type 1 S1P receptor expression decreased during the differentiation of IgM(+)B220(+) B cells to IgA(+)B220(+) B cells, but recovered on IgA(+)B220(-) plasmablasts for their emigration from the PPs.

Cutting edge: Langerin+ dendritic cells in the mesenteric lymph node set the stage for skin and gut immune system cross-talk.

Topical transcutaneous immunization (TCI) presents many clinical advantages, but its underlying mechanism remains unknown. TCI induced Ag-specific IgA Ab-secreting cells expressing CCR9 and CCR10 in the small intestine in a retinoic acid-dependent manner. These intestinal IgA Abs were maintained in Peyer's patch-null mice but abolished in the Peyer's patch- and lymph node-null mice.

Biological characterisation of a recombinant Atlantic salmon type I interferon synthesized in Escherichia coli.

Type I (alpha/beta) interferons (IFNs) are a family of cytokines that stimulate the expression of numerous proteins that mediate an antiviral state in uninfected cells. Two Atlantic salmon (Salmo salar) IFN-alpha (SasaIFN-alpha1 & 2) genes have previously been cloned and both were found to contain a putative N-linked glycosylation site. Recombinant SasaIFN-alpha1 (rSasaIFN-alpha1) produced in eukaryotic systems has repeatedly been shown to confer antiviral properties.

Sphingosine 1-phosphate-dependent trafficking of peritoneal B cells requires functional NFkappaB-inducing kinase in stromal cells.

We previously reported that sphingosine 1-phosphate (S1P) regulates peritoneal B-cell trafficking and subsequent intestinal IgA production, but the underlying mechanisms remain obscure. We demonstrate here that nuclear factor kappaB-inducing kinase (NIK) is involved in the regulation of S1P-mediated trafficking of peritoneal B cells. Although peritoneal B cells from NIK-mutated alymphoplasia (aly) mice expressed type 1 S1P receptor (S1P(1)) at comparable levels and demonstrated normal migration toward S1P, aly peritoneal B cells showed decreased sensitivity to FTY720, an S1P(1) modulator.