Review on pathogenicity mechanism of enterotoxigenic Escherichia coli and vaccines against it.

Enterotoxigenic Escherichia coli (ETEC) is the most common cause of diarrhea in children. Colonization factors (CFs) and LT enterotoxin are the major ETEC candidate vaccines. To cause disease, ETEC must adhere to the epithelium of the small intestine by means of CFs. Watery diarrhea is produced due to the effects of the enterotoxins. Vaccine development against ETEC has been identified as an important primary prevention strategy in developing countries and for travelers to these regions. Mucosal immunization can cause secretory IgA antibody (sIgA) responses that prevents the attachment of bacteria to the intestine and are of particular importance for provide protection against ETEC infection. The design of multivalent ETEC vaccine containing various colonization factors and ETEC toxin may provide protection against a wide range of bacterial strains. In this review, the importance and pathogenesis of ETEC, and the latest ETEC vaccine research results are discussed.

Does sensitization to foods in adults occur always in the gut?

It is widely accepted that, under normal conditions, the contact between allergens and the immune system via the gut results in immune tolerance. Thus, it is rather surprising that normal adults may become sensitized to foods that they have consumed a number of times without any consequence. However, the medical literature is crowded with reports suggesting that sensitization to food allergens may occur outside the intestinal tract in many instances. The present article reviews and discusses current data suggesting, either directly or indirectly, a possible initiation of food allergy in the respiratory tract or in the skin in the light of recent findings about mechanisms of tolerance and sensitization.

Pollen and plant food profilin allergens show equivalent IgE reactivity.

BACKGROUND: Profilins are commonly involved in polysensitization of allergic patients; therefore, appropriate markers should be used in component-resolved diagnosis. OBJECTIVE: To evaluate the immunological equivalence between profilins from pollens and plant-derived foods, to be used in component-resolved diagnosis. METHODS: Specific immunoglobulin (Ig) G antibodies against pollen and fruit profilins, as well as sera from patients allergic to mustard, melon, or olive pollen, were used. Purified profilins from mustard seeds, fruit melon, and chenopod and birch pollen were assayed in immunoblotting, enzyme-linked immunosorbent assay (ELISA), and ELISA inhibition assays. RESULTS: Significant correlation was found in the response of purified profilins by ELISA and immunoblotting for both specific IgG and IgE. The highest levels of IgE binding were obtained for olive pollen-allergic patients, which could be related to the route of sensitization. The responses of individual patients to profilins were also similar and independent of the sensitizing source. The inhibition between pairs of allergens was generally higher than 70%, indicating that profilins share most of the IgE epitopes. Modeling of mimotopes in the conformational structure of the implicated profilins supports their strong cross-reactivity obtained experimentally. CONCLUSIONS: No correlation exists between the level of IgE response of individual patients to specific profilins and the corresponding theoretical sensitizing source, suggesting that the sensitization could be attributable to any profilin present in the environment of the patients. This would bear out the use of most profilins as a common marker for polysensitization in component-resolved diagnosis and for therapeutic approaches.

Differences among pollen-allergic patients with and without plant food allergy.

BACKGROUND: A considerable number of pollen-allergic patients develops allergy to plant foods, which has been attributed to cross-reactivity between food and pollen allergens. The aim of this study was to analyze the differences among pollen-allergic patients with and without plant food allergy. METHODS: Eight hundred and six patients were recruited from 8 different hospitals. Each clinical research group included 100 patients (50 plant food-allergic patients and 50 pollen-allergic patients). Diagnosis of pollen allergy was based on typical case history of pollen allergy and positive skin prick tests. Diagnosis of plant-food allergy was based on clear history of plant-food allergy, skin prick tests and/or plant-food challenge tests. A panel of 28 purified allergens from pollens and/or plant foods was used to quantify specific IgE (ADVIA-Centaur® platform). RESULTS: Six hundred and sixty eight patients (83%) of the 806 evaluated had pollen allergy: 396 patients with pollen allergy alone and 272 patients with associated food and pollen allergies. A comparison of both groups showed a statistically significant increase in the food and pollen allergy subgroup in frequency of: (1) asthma (47 vs. 59%; p < 0.001); (2) positive skin test results to several pollens: Plantago, Platanus, Artemisia, Betula, Parietaria and Salsola (p < 0.001); (3) sensitization to purified allergens: Pru p 3, profilin, Pla a 1 - Pla a 2, Sal k 1, PR-10 proteins and Len c 1. CONCLUSION: Results showed relevant and significant differences between both groups of pollen-allergic patients depending on whether or not they suffered from plant-derived food allergy.

Cypress pollen does not cross-react to plant-derived foods.

BACKGROUND AND OBJECTIVE: Some studies hypothesize the existence of cross-reactivity between allergy to Cupressus sempervirens pollen and plant-derived foods. We aimed to assess whether this holds true. METHODS: 72 patients monosensitized to cypress pollen were investigated for food allergy to peach, apple, tomato and Juniperius oxycedrus berry. RESULTS: No patient had a history of clinical allergy or showed in-vitro or in-vitro reactivity to peach, apple, and tomato. Two patients scored positive on SPT with Juniperius oxycedrus berry but in-vitro tests ruled out cross-reactivity with the corresponding pollen. CONCLUSION: Airborne allergy to Cupressaceae pollen is not associated with allergy to plant-derived foods.

[Correlation of oral allergy syndrome due to plant-derived foods with alder pollen, rbet v 1 and rbet v 2 sensitization in Yokohama region].

BACKGROUND/AIM: Oral allergy syndrome (OAS) to plant foods is often caused by cross-reactivity to pollen. We investigated whether there was any significant correlation between sensitization to the pollen of alder and Japanese cedar flying off in spring and prevalence of OAS in Yokohama region. METHODS: We measured specific IgE antibodies (CAP-FEIA: CAP) against alder and Japanese cedar in 337 outpatients with skin allergy in 2005 (M:F=167:170, 33.4 years of age, on the average). In the patients who showed positive response to CAP against alder and Japanese cedar, we also tested response to CAP against rBet v 1 and rBet v 2. In addition, we statistically analyzed whether there was any correlation between prevalence of OAS and sensitization to the pollen. RESULTS: Ratio of positive response to CAP against alder was 23.4% (79 cases) while that to CAP against Japanese cedar was 73.7% (244 cases). Response to CAP against rBet v 1 and rBet v 2 was tested in 55 cases, and the ratio of positive response to CAP against rBet v 1 was 43.6% (24 cases) while that to CAP against rBet v 2 was 27.3% (15 cases). Prevalence of OAS showed a significant positive correlation (p<0.001) with sensitization to alder, but no correlation with sensitization to Japanese cedar. CONCLUSION: It was suggested that sensitization to alder pollen would be involved in prevalence of OAS in Yokohama region.

Plant food allergy: Influence of chemicals on plant allergens.

Plant-derived foods are the most common allergenic sources in adulthood. Owing to the rapidly increasing prevalence of plant food allergies in industrialized countries, the environmental factors are suspected to play a key role in development of allergic sensitization. The present article provides an overview of ways by which chemicals may influence the development and severity of allergic reactions to plant foods, with especial focus on plant allergens up-regulated under chemical stress. In plants, a substantial part of allergens have defense-related function and their expression is highly influenced by environmental stress and diseases. Pathogenesis-related proteins (PR) account for about 25% of plant food allergens and some are responsible for extensive cross-reactions between plant-derived foods, pollen and latex allergens. Chemicals released by anthropogenic sources such as agriculture, industrial activities and traffic-related air pollutants are potential drivers of the increasing sensitization to allergenic PRs by elevating their expression and by altering their immunogenicity through post-translational modifications. In addition, some orally-taken chemicals may act as immune adjuvants or directly trigger non-IgE mediated food allergy. Taken together, the current literature provides an overwhelming body of evidence supporting the fact that plant chemical exposure and chemicals in diet may enhance the allergenic properties of certain plant-derived foods.

Detection of some safe plant-derived foods for LTP-allergic patients.

BACKGROUND: Lipid transfer protein (LTP) is a widely cross-reacting plant pan-allergen. Adverse reactions to Rosaceae, tree nuts, peanut, beer, maize, mustard, asparagus, grapes, mulberry, cabbage, dates, orange, fig, kiwi, lupine, fennel, celery, tomato, eggplant, lettuce, chestnut and pineapple have been recorded. OBJECTIVE: To detect vegetable foods to be regarded as safe for LTP-allergic patients. METHODS: Tolerance/intolerance to a large spectrum of vegetable foods other than Rosaceae, tree nuts and peanut was assessed by interview in 49 subjects monosensitized to LTP and in three distinct groups of controls monosensitized to Bet v 1 (n = 24) or Bet v 2 (n = 18), or sensitized to both LTP and birch pollen (n = 16), all with a history of vegetable food allergy. Patients and controls underwent skin prick test (SPT) with a large spectrum of vegetable foods. The absence of IgE reactivity to foods that were negative in both clinical history and SPT was confirmed by immunoblot analysis and their clinical tolerance was finally assessed by open oral challenge (50 g per food). RESULTS: All patients reported tolerance and showed negative SPT to carrot, potato, banana and melon; these foods scored positive in SPT and elicited clinical symptoms in a significant proportion of patients from all three control groups. All patients tolerated these four foods on oral challenge. Immunoblot analysis confirmed the lack of IgE reactivity to these foods by LTP-allergic patients. CONCLUSION: Carrot, potato, banana and melon seem safe for LTP-allergic patients. This finding may be helpful for a better management of allergy to LTP.

[Oral allergy syndrome due to plant-derived foods: a clinical review of 63 patients over a period of 6 years].

BACKGROUND: The clinical features of many patients with oral allergy syndrome (OAS) due to plant-derived foods have rarely been reported in Japan. OBJECTIVES: We aimed to determine the causative foods of OAS due to plant-derived foods based on clinical features and skin prick tests (SPTs). Furthermore, we aimed to elucidate the association between causative foods and sensitized pollens in patients with OAS due to plant-derived foods. METHODS: SPTs and specific IgE measurements (CAP-FEIA: CAP) were performed in relation to foods and pollens in 118 patients with positive histories of OAS due to plant-derived foods. Patients with positive histories and with positive skin test responses were identified as having type I allergy to the causative foods. RESULTS: The mean age of 63 patients with positive histories and positive skin test responses was 29.2 years (range, 2-61 years), and there were twice as many females as male. The most frequent causative foods were found to be apple, peach, kiwi, and melon in 13, 12, 12, and 11 patients, respectively. CAP frequency was shown to be similar to that of SPT regarding apple, whereas it was less than that of SPT regarding melon, peach, and kiwi. A significant correlation between the frequencies of SPT and CAP was found regarding apple (r=0.39, p<0.05) but not peach, kiwi, and melon. Forty-one of 63 patients with OAS (66.1%) had pollinosis and/or allergic rhinitis. In patients with OAS due to apple, the positive ratio of CAP response against alder pollen was higher than that in patients with OAS due to melon. In patients with OAS due to melon, the positive ratio of CAP responses against ragweed pollen, grass pollen, and mugwort pollen was higher than that in patients with OAS due to apple. CONCLUSION: In this study, positive ratios of SPT and CAP tended to differ according to the causative food, showing a smaller potential for reaction than might be suggested by patient history. Therefore, for the time being it would be more accurate to use a skin test for the diagnosis of OAS due to plant-derived foods.

Plant food allergens--structural and functional aspects of allergenicity.

The three dominating plant food allergen groups belong to the prolamin and cupin superfamilies and to the family 10 of pathogenesis-related proteins. The prolamin superfamily comprises allergenic 2S albumins, nonspecific lipid transfer proteins and cereal alpha-amylase/trypsin inhibitors. These allergens have related structures and are stable to thermal processing and proteolysis. The cupin superfamily comprises the allergenic 7S and 11S globulin storage proteins from peanuts, soybean and tree nuts which are heat stable and can form immunogenicity enhancing aggregates. The Bet v 1 family of allergens includes tree pollinosis-associated food allergens with low stability which induce the symptoms of the oral allergy syndrome.

Plant-made vaccines: biotechnology and immunology in animal health.

The use of plants as production systems for vaccine antigens has been actively investigated over the last 15 years. The original research focused on the value of this expression system for oral delivery based on the hypothesis that plant-expressed antigens would be more stable within the digestive tract and would allow for the use of the oral route of administration to stimulate a mucosal immune response. However, while first conceived for utility via the oral route, plant-made antigens have also been studied as classical immunogens delivered via a needle to model animal systems. Antigens have been expressed in a number of whole plant and cell culture systems. Several alternative expression platforms have been developed to increase expression of antigens or to elicit preferred immunological responses. The biotechnological advances in plant expression and the immunological testing of these antigens will be reviewed in this paper focusing primarily on diseases of livestock and companion animals.

[Cross reactivity of food allergens and its clinical relevance]. / Allergies alimentaires croisées: quelles nouveautés ?

Cross-reactions between food allergens and other allergens are a major focus of interest. They include cross-allergies between Betulaceae and Compositae pollen, and also between fruits and vegetables (Prunoideae and Apiaceae). Cross-allergies between animal allergens include mites, cockroaches and crustaceans, milk and meat, animal epithelia, meat and egg. Cross-reactivity results from homology between protein sequences, and is highly likely when this homology reaches about 70%. Phylogenetically similar proteins occur in all species and are known as pan allergens. Profilins, Bet v1 homologues, and lipid transfer proteins have varying degrees of clinical relevance. The involvement of cross-reactivity in the persistence of sensitization and in allergic disorders is unclear. The consequences of cross-reactivity during specific immunotherapy with total allergenic extracts are random. Interpretation of biological tests of IgE binding is also biased by cross-reactivity. The use of panels of major recombinant allergens should help to identify specific sensitization profiles as well as clinically relevant sensitization. Cross-reactivity between epitopes of inhalants and of food allergens may perpetuate and intensify allergic disorders. The consequences of cross-reactivity between allergens and autologous proteins are unknown.

Atopic allergens of plant foods.

The exact knowledge of what structural characteristics of an antigen are responsible for its allergenicity may not be available for several years. However, it is striking that the majority of the plant food allergens are clustered within a few protein families, and these are reviewed in this article. In most cases, plant food allergens are proteins that ensure the survival of the species as either seed storage proteins or proteins that are actively involved in the defence of the organism.

Digestion stability as a criterion for protein allergenicity assessment.

Assessing the allergenic potential of transgenic proteins introduced into genetically engineered food remains a critical part of the overall safety assessment of these foods. Stability to digestion has been proposed as one of the steps in the decision tree approach to assess the allergenic potential of transgenic proteins. The validity of digestion stability as a criterion for protein allergenicity assessment, however, has encountered some criticism in recent years. This chapter gives an overview of the rationale behind the use of digestion stability as a criterion for protein allergenicity assessment and reviews the available data that may or may not support its use. The application of in vitro digestion assays for the assessment of allergenic potential of novel proteins and the factors that affect the assay results are also discussed. There is a need to establish standardized assay conditions so that direct comparison of results from different laboratories can be made. Consensus also needs to be reached on relating the measured digestibility to the allergenic potential of proteins.

Approaches to assessment of the allergenic potential of novel proteins in food from genetically modified crops.

The safety assessment of food derived from genetically modified plants continues to attract considerable attention. Among the important issues that need to be considered is whether the products of novel genes introduced into crop plants will have the potential to induce allergic sensitization or to elicit allergic disease. Hierarchical approaches to allergenicity testing have been proposed, and these incorporate evaluation of the structural and sequence homology and serological identity of novel proteins with known allergens, measurement of resistance to proteolytic digestion, and assessment of allergenic potential using animal models. Accounts of these approaches are available elsewhere, and it is not the purpose of this article to provide a detailed critique of specific methods. Our intention is rather to look more broadly at the strategy for assessment of allergenic potential, the challenges such assessments pose for the practicing toxicologist, and how some of these might best be addressed.

Immunoglobulins anti-endonuclease 32 kDa from Cucurbita pepo var patissonina affect process of DNA synthesis.

Immunoglobulins anti-endonuclease 32 kDa inhibit DNA synthesis. We observed that low concentrations of IgGs (about 50 micrograms IgG per 1 x 10(6) cell nuclei) temporary inhibit DNA synthesis. This inhibition concerns only the synthesis of DNA bound to the nuclear matrix (associated with isolated nuclear matrix). Preincubation of cell nuclei of White bush with IgG generates longer DNA fragments than in controls. Involvement of the 32 kDa endonuclease or an endonuclease-65 kDa protein complex from the nuclear matrix in replication or structural organisation of replication is considered.

Daucus carrota (carrot)--a selective bacteriosorbent.

1) An extract of D. carrota induces agglutination of most serotypes of S. mutans but not of S. salivarius or S. mitis. 2) If added to a suspension of mixed bacteria, a piece of D. carrota may selectively sorb S. mutans while S. salivarius and S. mitis only are affected to a minor degree. 3) A saliva coat on the bacteria may reduce the uptake of S. mutans to D. carota but does not totally prevent it.

Edible vaccines.

The ultimate vaccine is an oral vaccine which given once protects against a multitude of diseases. Furthermore this ultimate vaccine needs to be very stable and inexpensive to produce. Probably this latter condition can be met only if the vaccines are produced in plants. Such vaccines are called 'edible vaccines'. Edible vaccines can be produced in plants in many ways. Using recombinant plantvirus, CPMV, it was shown that plants can produce massive amounts of chimaeric virus particles which protect after a single injection the target animal against disease. The final step, oral administration, is being addressed at present. Preliminary experiments by others suggest that this step may be solved sooner than expected.

Transgenic resistance.

Transgenic resistance to plant viruses is an important technology for control of plant virus infection, which has been demonstrated for many model systems, as well as for the most important plant viruses, in terms of the costs of crop losses to disease, and also for many other plant viruses infecting various fruits and vegetables. Different approaches have been used over the last 28 years to confer resistance, to ascertain whether particular genes or RNAs are more efficient at generating resistance, and to take advantage of advances in the biology of RNA interference to generate more efficient and environmentally safer, novel "resistance genes." The approaches used have been based on expression of various viral proteins (mostly capsid protein but also replicase proteins, movement proteins, and to a much lesser extent, other viral proteins), RNAs [sense RNAs (translatable or not), antisense RNAs, satellite RNAs, defective-interfering RNAs, hairpin RNAs, and artificial microRNAs], nonviral genes (nucleases, antiviral inhibitors, and plantibodies), and host-derived resistance genes (dominant resistance genes and recessive resistance genes), and various factors involved in host defense responses. This review examines the above range of approaches used, the viruses that were tested, and the host species that have been examined for resistance, in many cases describing differences in results that were obtained for various systems developed in the last 20 years. We hope this compilation of experiences will aid those who are seeking to use this technology to provide resistance in yet other crops, where nature has not provided such.