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Non-human primate (NHP) cytomegaloviruses (CMVs) can be genetically modified to induce unconventional CD8+ T cell responses that target epitopes presented by MHC-II and MHC-E; the latter is an MHC-Ib molecule with limited polymorphism, primarily known for regulating natural killer (NK) cell reactivity. These unconventional responses to diverse antigens are inhibited by specific gene products in wild-type NHP CMVs, and are enabled by deletion of these genes. Based on understanding how CMV controls CD8+ T cell priming, Rhesus (Rh) CMV-based vaccine vectors can be programmed to elicit vaccine insert-specific CD8+ T cell responses that recognize peptide epitopes presented by MHC-Ia, MHC-II, and MHC-E, alone and in combination, generating the first vaccine with programmable CD8+ T cell epitope targeting. RhCMV-based vaccine vectors that elicit simian immunodeficiency virus (SIV)-specific, MHC-E-restricted CD8+ T cells, but not other conventional or unconventional MHC restriction CD8+ T cell response types, mediate a potent form of efficacy against highly pathogenic SIV; viral replication is completely arrested in early primary infection, and virus is cleared over ensuing months to several years. SIV replication arrest protection occurs in ~60% of vaccinees with MHC-E-restricted CD8+ T cell responses and correlates with a vaccine-induced innate immune response featuring IL-15 signaling. All known RhCMV gene product-mediated CD8+ T cell response programming functions are conserved in the human CMV genome, suggesting that HIV-1-specific MHC-E-restricted CD8+ T cells and their associated replication arrest and clear efficacy could be recapitulated in humans. HIV and SIV are highly immune evasive viruses with few immune vulnerabilities. The discovery that CMV vector-programmed MHC-E-restricted CD8+ T cells can mediate complete replication arrest of primary SIV infection with subsequent viral clearance indicates the existence of a previously unknown Achilles' heel that offers promise for vaccines or immunotherapeutics for HIV, and possibly other infectious diseases or cancer. The initial development of cytomegalovirus (CMV) as a vaccine vector for HIV/simian immunodeficiency virus (SIV) was predicated on its potential to pre-position high-frequency, effector-differentiated, CD8+ T cells in tissues for immediate immune interception of nascent primary infection. This goal was achieved and also led to the unexpected discoveries that non-human primate (NHP) CMVs can be programmed to differentially elicit CD8+ T cell responses that recognize viral peptides via classical MHC-Ia, and/or MHC-II, and/or MHC-E, and that MHC-E-restricted CD8+ T cell responses can uniquely mediate stringent arrest and subsequent clearance of highly pathogenic SIV, an unprecedented type of vaccine-mediated protection. These discoveries delineate CMV vector-elicited MHC-E-restricted CD8+ T cells as a functionally distinct T cell response with the potential for superior efficacy against HIV-1, and possibly other infectious agents or cancers. [ABSTRACT FROM AUTHOR]

The successional changes in the early intestinal microbiota occur concomitantly with the development, expansion, and education of the mucosal immune system. Although great attention of researchers has been focused on understanding the linkage between microbiota and immune functions, many essential details of the symbiotic relationship between the intestinal pioneer microbiota and the avian immune system remain to be discovered. This study was conducted to understand the impact of different early life intestinal colonizers on innate and adaptive immune processes in chicks and further identify immune-associated proteins expressed in the intestinal tissue. To accomplish it, we performed an in ovo application of two apathogenic Enterobacteriaceae isolates and lactic acid bacteria (L) to determine their influences on the intestinal proteome profile of broilers at the day of hatch (DOH) and at 10 days old. The results indicated that there were predicted biological functions of L-treated chicks associated with the activation and balanced function of the innate and adaptive immune systems. At the same time, the Enterobacteriaceae- exposed birds presented dysregulated immunological mechanisms or downregulated processes related to immune development. Those findings suggested that a proper immune function was dependent on specific gut microbiota exposure, in which the prenatal probiotic application may have favored the fitting programming of immune functions in chicks. [ABSTRACT FROM AUTHOR]

The successional changes in the early intestinal microbiota occur concomitantly with the development, expansion, and education of the mucosal immune system. Although great attention of researchers has been focused on understanding the linkage between microbiota and immune functions, many essential details of the symbiotic relationship between the intestinal pioneer microbiota and the avian immune system remain to be discovered. This study was conducted to understand the impact of different early life intestinal colonizers on innate and adaptive immune processes in chicks and further identify immune-associated proteins expressed in the intestinal tissue. To accomplish it, we performed an in ovo application of two apathogenic Enterobacteriaceae isolates and lactic acid bacteria (L) to determine their influences on the intestinal proteome profile of broilers at the day of hatch (DOH) and at 10 days old. The results indicated that there were predicted biological functions of L-treated chicks associated with the activation and balanced function of the innate and adaptive immune systems. At the same time, the Enterobacteriaceae-exposed birds presented dysregulated immunological mechanisms or downregulated processes related to immune development. Those findings suggested that a proper immune function was dependent on specific gut microbiota exposure, in which the prenatal probiotic application may have favored the fitting programming of immune functions in chicks.

There is substantial epidemiological and mechanistic evidence that the increase in allergic disease and asthma in many parts of the world in part relates to changes in microbial exposures and diet acting via the composition and metabolic products of the intestinal microbiome. The majority of research in this field has focused on the gut microbiome during infancy, but it is increasingly clear that the maternal microbiome during pregnancy also has a key role in preventing an allergy-prone immune phenotype in the offspring. The mechanisms by which the maternal microbiome influences the developing fetal immune system include alignment between the maternal and infant regulatory immune status and transplacental passage of microbial metabolites and IgG. Interplay between microbial stimulatory factors such as lipopolysaccharides and regulatory factors such as short-chain fatty acids may also influence on fetal immune development. However, our understanding of these pathways is at an early stage and further mechanistic studies are needed. There are also no data from human studies relating the composition and metabolic activity of the maternal microbiome during pregnancy to the offspring's immune status at birth and risk of allergic disease. Improved knowledge of these pathways may inform novel strategies for tackling the increase in allergic disorders in the modern world. [ABSTRACT FROM AUTHOR]

Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Although the pathophysiological effects of ELA are varied, there may be a unifying role for the immune system in all of the long-term pathologies such as chronic inflammatory disorders (autoimmune diseases, allergy, and asthma). Recently, significant efforts have been made to elucidate the long-term effects ELA has on immune function, as well as the mechanisms underlying these immune changes. In this review, we focus on data from human studies investigating immune parameters in relation to post-natal adverse experiences. We describe the current understanding of the ‘ELA immune phenotype’, characterized by inflammation, impairment of the cellular immune system, and immunosenescence. However, at present, data addressing specific immune functions are limited and there is a need for high-quality, well powered, longitudinal studies to unravel cause from effect. Besides the immune system, also the stress system and health behaviors are altered in ELA. We discuss probable underlying mechanisms based on epigenetic programming that could explain the ELA immune phenotype and whether this is a direct effect of immune programming or an indirect consequence of changes in behavior or stress reactivity. Understanding the underlying mechanisms will help define effective strategies to prevent or counteract negative ELA-associated outcomes. [ABSTRACT FROM AUTHOR]

Prenatal glucocorticoid therapy is indicated in preterm delivery to prevent respiratory distress. This study was designed to evaluate the age-dependent effects of prenatal dexamethasone (DEX) therapy on the immune system using a rat model. Pregnant Sprague-Dawley rats received an intraperitoneal injection of DEX (0.1 mg/kg/day) or saline (VEH) over gestational days 14-20. Male offspring were sacrificed at postnatal day 7 (D7; infant stage), D120 (young adult stage), and D180 (adult stage) for evaluation of leukocyte subsets and isolation of splenocytes. The production of innate and adaptive immune cytokines was assessed from the culture supernatants of splenocytes, stimulated with lipopolysaccharide and concanavalin A, respectively. For innate cytokines, the levels of interferon gamma inducible protein 10 were significantly higher, but those of tumor necrosis factor-α were significantly lower, in the culture medium of splenocytes prepared from the DEX group at D120 than those in the VEH group. For adaptive cytokines, the levels of interleukin-4 (IL-4) were significantly higher at D7 and those of IL-10 were significantly higher at D120 after prenatal exposure to DEX. We also showed that the expression level of IL-4 mRNA was significantly higher in splenocytes prepared from the DEX group at D7, compared with the VEH group. Importantly, the mRNA expression level of T-bet, a key transcription factor for immune cells, was greatly decreased in the spleen of the DEX group at D7, compared with the VEH group. In conclusion, prenatal dexamethasone exposure shows the greater impact on immune responses of their male offspring in early life. [ABSTRACT FROM AUTHOR]

A novel algorithm parallel partheno genetic algorithm based on the immune programming（IPPPGA） was proposed,the algorithm analogies to the concept and theory of immunity in biotic science and unifies the parallel compu-tation thought,after analyzing the advantages and disadvantages of the partheno genetic algorithm.The theory analysis and experimental results show that the algorithm not only effectively keeps population diversity,but also alleviates the undulate phenomenon in evolutionary latter stages,meanwhile increases the convergent speed and computational effi-ciency greatly.

Exposures during the early life (periconceptional, prenatal and early postnatal) period are increasingly recognized as playing an important role in the aetiology of chronic non-communicable diseases (NCD), including coronary heart disease, stroke, hypertension, Type 2 diabetes and osteoporosis. The ‘Developmental Origins of Health and Disease’ (DOHaD) hypothesis states that these disorders originate through unbalanced nutrition early in life and risk is highest when there is a ‘mismatch’ between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in countries where an excess of infants are born with low birth weight and where there is a rapid transition to nutritional adequacy or excess in adulthood. Here, I will review data from work conducted in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomized controlled trials of nutritional supplementation in pregnancy and the ‘experiment of nature’ that seasonality in this region provides, we have investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs. [ABSTRACT FROM PUBLISHER]

We propose CCRank, the first parallel framework for learning to rank based on evolutionary algorithms (EA), aiming to significantly improve learning efficiency while maintaining accuracy. CCRank is based on cooperative coevolution (CC), a divide-and-conquer framework that has demonstrated high promise in function optimization for problems with large search space and complex structures. Moreover, CC naturally allows parallelization of sub-solutions to the decomposed sub-problems, which can substantially boost learning efficiency. With CCRank, we investigate parallel CC in the context of learning to rank. We implement CCRank with three EA-based learning to rank algorithms for demonstration. Extensive experiments on benchmark datasets in comparison with the state-of-the-art algorithms show the performance gains of CCRank in efficiency and accuracy. [ABSTRACT FROM PUBLISHER]

Smart home integrates disaster protection, medical care, entertainment and energy-saving systems, making the living environment more secure and comfortable. This paper investigates the demand response achieved by the “smart energy management system” in a smart home environment, and aims to obtain the optimal temperature scheduling for air-conditioning according to the day-ahead electricity price and outdoor temperature forecasts. Because the retail electricity price and temperature are predicted 24 h in advance and there exists uncertainty, the predicted retail electricity prices and temperatures are modeled by the fuzzy set. The immune clonal selection programming is employed to determine the day-ahead 24-h temperature schedule for air-conditioning. The electricity expense is hence minimized while comfort is still retained. The simulation result shows the applicability of the proposed method. [ABSTRACT FROM PUBLISHER]

Abstract: Recent research links nutritional exposures early in life with alterations in functional immunity that persist beyond childhood. Here we investigate predictors of antibody response to polysaccharide vaccines in a cohort of Gambian adults with detailed records from birth and early infancy available. 320 adults were given a single dose of a Vi polysaccharide vaccine for Salmonella typhi and a 23-valent capsular polysaccharide pneumococcal vaccine. Anti-Vi antibody levels and antibodies against 4 pneumococcal serotypes (1, 5, 14 and 23F) were measured in serum samples collected at baseline and then 14 days following vaccination and compared to data available from birth and early infancy. Post-vaccination antibody titres to serotype 14 of the pneumococcal vaccine were negatively associated with rate of growth from birth to three months of age, infant weight at 12 months of age and season of birth, but no other associations were observed with early-life exposures. The strongest predictor of antibody levels was pre-vaccination antibody titres, with adult height and serum neopterin levels at time of vaccination also implicated. The current study does not support the hypothesis that nutritional exposures early in life consistently compromise antibody response to polysaccharide vaccines administered in young adulthood. [Copyright &y& Elsevier]

Objective: The fetal inflammatory response syndrome (FIRS) is considered the fetal counterpart of the systemic inflammatory response syndrome (SIRS), which can be caused by infection and non-infection-related insults. Although the initial response is mediated by pro-inflammatory signals, the control of this response is achieved by anti-inflammatory mediators which are essential for the successful outcome of the affected individual. Interleukin (IL)-19 is capable of stimulating the production of IL-10, a major anti-inflammatory cytokine, and is a potent inducer of the T-helper 2 (Th2) response. The aim of this study was to determine if there is a change in umbilical cord plasma IL-19 and IL-10 concentrations in preterm neonates with and without acute funisitis, the histologic counterpart of FIRS. Methods: A case-control study was conducted including 80 preterm neonates born after spontaneous labor. Neonates were classified according to the presence ( n = 40) or absence of funisitis ( n = 40), which is the pathologic hallmark of FIRS. Neonates in each group were also matched for gestational age. Umbilical cord plasma IL-19 and IL-10 concentrations were determined by ELISA. Results: 1) The median umbilical cord plasma IL-19 concentration was 2.5-fold higher in neonates with funisitis than in those without funisitis (median 87 pg/mL; range 20.6-412.6 pg/mL vs. median 37 pg/mL; range 0-101.7 pg/mL; p < 0.001); 2) newborns with funisitis had a significantly higher median umbilical cord plasma IL-10 concentration than those without funisitis (median 4 pg/mL; range 0-33.5 pg/mL vs. median 2 pg/mL; range 0-13.8 pg/mL; p < 0.001); and 3) the results were similar when we included only patients with funisitis who met the definition of FIRS by umbilical cord plasma IL-6 concentrations ≥ 17.5 pg/mL ( p < 0.001). Conclusion: IL-19 and IL-10 are parts of the immunologic response of FIRS. A subset of fetuses with FIRS had high umbilical cord plasma IL-19 concentrations. In utero exposure to high systemic concentrations of IL-19 may reprogram the immune response. [ABSTRACT FROM AUTHOR]

Linoleic acid and α-linolenic acid are essential fatty acids (eFAs) and have to be acquired from the diet. eFAs are the precursors for long-chain polyunsaturated fatty acids (lcPUFAs), which are important immune-modulating compounds. lcPUFAs can be converted into eicosanoids and other mediators. They affect membrane structure and fluidity and can alter gene expression. There has been a marked change in dietary fatty acid intake over the last several decades. Since eFAs are acquired from the diet and immune development occurs mainly perinatally, the maternal diet may influence fetal and neonatal eFA levels, and thereby lcPUFA status, and thus immune development and function. To study whether early exposure to eFAs can program immune function, mice were fed diets varying in the ratio of ω-3 to ω-6-eFAs during pregnancy and/or lactation. After weaning, pups received a Western-style diet. At 11 weeks of age, the effects of maternal diet on the offspring's allergic and vaccination responses were examined using the T-helper 2 driven ovalbumin-induced allergy model and the T-helper 1 driven influenza-vaccination model, respectively. Offspring of dams fed a high α-linolenic acid diet during lactation showed an enhanced vaccination response. As diets with either low or high ω-3/ω-6-eFA ratio attenuated the T-helper 2 allergic response, the high α-linolenic acid diet fed during lactation had the most pronounced effect. These results indicate that there is a programming effect of maternal diet on the offspring's immune response and that in mice the window of greatest susceptibility to maternal dietary intervention is the lactation/suckling period. [ABSTRACT FROM PUBLISHER]

This paper describes Grammar-based Immune Programming (GIP) for evolving programs in an arbitrary language by immunological inspiration. GIP is based on Grammatical Evolution (GE) in which a grammar is used to define a language and decode candidate solutions to a valid representation (program). However, by default, GE uses a Genetic Algorithm in the search process while GIP uses an artificial immune system. Some modifications are needed of an immune algorithm to use a grammar in order to efficiently decode antibodies into programs. Experiments are performed to analyze algorithm behavior over different aspects and compare it with GEVA, a well known GE implementation. The methods are applied to identify a causal model (an ordinary differential equation) from an observed data set, to symbolically regress an iterated function f( f( x)) = g( x), and to find a symbolic representation of a discontinuous function. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we propose RankIP, the first immune programming (IP) based ranking function discovery approach. IP is a novel evolution based machine learning algorithm with the principles of immune systems, which is verified to be superior to Genetic Programming (GP) on the convergence of algorithm according to their experimental results in Musilek et al. (2006). However, such superiority of IP is mainly demonstrated for optimization problems. RankIP adapts IP to the learning to rank problem, a typical classification problem. In doing this, the solution representation, affinity function, and high-affinity antibody selection require completely different treatments. Besides, two formulae focusing on selecting best antibody for test are designed for learning to rank. Experimental results demonstrate that the proposed RankIP outperforms the state-of-the-art learning-based ranking methods significantly in terms of and . [Copyright &y& Elsevier]

Background Allergic diseases cause a large and increasing burden in developed countries and in urban centres in middle-income countries. The causes of this increase are unknown and, currently, there are no interventions to prevent the development of allergic diseases. The ‘hygiene hypothesis’ has tried to explain the increase through a reduction in the frequency of childhood infections causing a failure to program the immune system for adequate immune regulation. Intestinal helminth parasites are prevalent in childhood in developing countries and are associated with a lower prevalence of allergen skin test reactivity and asthma. Objectives To investigate whether children who had intestinal helminth infections during early childhood have a lower prevalence of allergen skin test reactivity later in childhood. Methods We re-visited a population of 1055 children from whom stool samples had been collected for detection of intestinal helminth infections for another study, and collected new stool samples and performed allergen skin prick testing. Information on potential confounding variables was collected. Results Children with heavy infections with Trichuris trichiura in early childhood had a significantly reduced prevalence of allergen skin test reactivity in later childhood, even in the absence of T. trichiura infection at the time of skin testing in later childhood. Conclusion Early heavy infections with T. trichiura may protect against the development of allergen skin test reactivity in later childhood. Novel treatments to program immune-regulation in early childhood in a way that mimics the effects of early infections with T. trichiura may offer new strategies for the prevention of allergic disease. [ABSTRACT FROM AUTHOR]

Summary: We have previously shown that the generation of antibodies to a polysaccharide vaccine (Typhim Vi) is compromised in Pakistani adults born of a lower birth weight. To assess whether this represents a true B-cell-dependent deficit, we revaccinated subjects with a second dose of the same vaccine and with a polysaccharide–protein conjugate vaccine to a different polysaccharide antigen (conjugated Haemophilus influenzae type b (Hib) vaccine). Anti-Vi IgG levels remained positively correlated with birth weight (p =0.0284) but no associations were observed between anti-Hib IgG levels and size at birth. These findings indicate that small size at birth results in a poor antibody response to vaccination with a polysaccharide antigen vaccine in adulthood, even following a second dose of the vaccine. No such association was observed in response to a polysaccharide–protein conjugate vaccine indicating an early-life programming effect on the generation of antibodies during a B-cell-dependent immune response. [Copyright &y& Elsevier]

Background: In rural Gambians, the season of birth strongly predicts adult mortality. Those born during the harvest season have longer life spans than do those born during the hungry season, and the deaths associated with infectious diseases suggest permanent early-life influences on immunity. Thymic measurements showed significantly smaller thymuses in infants born during the hungry season than in those born during the harvest season. The differences were greatest at 8 wk of age, a time when all infants were exclusively breastfed, which suggests the involvement of breast milk factors. Objective: This study tested whether thymic size differences reflect thymic output and ascertained whether thymic output is associated with breast milk interleukin 7 (IL-7) concentrations. Design: We studied thymic size and output in a prospective cohort of 138 Gambian infants born in either the hungry or the harvest season by measuring signal-joint T cell receptor-rearrangement excision circles (sjTRECs) at birth and at 8 wk of age. IL-7 concentrations in breast milk were measured by using an enzyme-linked immunosorbent assay. Results: By age 8 wk, those born in the hungry season had significantly lower sjTREC counts than did those born in the harvest season(0.97 and 2.12 sjTRECs/100 T cells, respectively; P = 0.006). At 1 wk postpartum, the breast milk of mothers of infants born in the hungry season had significantly lower IL-7 than did that of mothers of infants born in the harvest season (79 and 100 pg/mL, respectively; P = 0.02). The findings were similar at 8 wk postpartum. Conclusion: These data show a plausible pathway linking external seasonal insults to mothers with thymic development in their infants, which suggests possible implications for long-term programming of immunity. [ABSTRACT FROM AUTHOR]

Based on Immune Programming(IP), a novel Radial Basis Function (RBF) network designing method is proposed. Through extracting the preliminary knowledge about the width of the basis function as the vaccine to form the immune operator, the algorithm reduces the searching space of canonical algorithm and improves the convergence speed. The application of the RBF network trained with the algorithm in the modulation-style recognition of radar signals demonstrates that the network has a fast convergence speed with good performances. [ABSTRACT FROM AUTHOR]