Search

Purpose: To study the therapeutic effect of hemagglutinin-2 and fimbrial (HA2-FimA) vaccine on experimental periodontitis in rats. Materials and Methods: The first batch of rats was divided into two groups and immunised with pure water or pVAX1-HA2- FimA at the age of 6, 7, and 9 weeks. After sacrificing the animals, total RNA was extracted from the spleens for RNA high-throughput sequencing (RNA-Seq) analysis. The second batch of rats was divided into four groups (A, B, C, D), and an experimental periodontitis rat model was established by suturing silk thread around the maxillary second molars of rats in groups B, C, and D for 4 weeks. The rats were immunised with pure water, pVAX1-HA2-FimA vaccine, empty pVAX1 vector, and pure water at 10, 11, and 13 weeks of age, respectively. Secretory immunoglobulin A (SIgA) antibodies and cathelicidin antimicrobial peptide (CAMP) levels in saliva were measured by enzyme-linked immunosorbent assay (ELISA). All rats were euthanised at 17 weeks of age, and alveolar bone loss was examined using micro-computed tomography (Micro-CT). Results: Through sequencing analysis, six key genes, including Camp, were identified. Compared with the other three groups, the rats in the periodontitis+pVAX1-HA2-FimA vaccine group showed higher levels of SIgA and CAMP (p < 0.05). MicroCT results showed significantly less alveolar bone loss in the periodontitis+pVAX1-HA2-FimA vaccine group compared to the periodontitis+pVAX1 group and periodontitis+pure water group (p < 0.05). Conclusion: HA2-FimA DNA vaccine can increase the levels of SIgA and CAMP in the saliva of experimental periodontitis model rats and reduce alveolar bone loss. [ABSTRACT FROM AUTHOR]

The prevalence of pain and dementia increases with age, affecting a significant percentage of the population due to aging. Both pathologies are connected through the inflammatory process, specifically through the tumor necrosis factor. The effect of this cytokine is mediated through the modulation of its TNFRI and TNFRII receptors, which are linked to the dementia process. In addition, immunoglobulins such as secretory immunoglobulin A (sIgA) have been recognized as one of the main biomarkers of pain in saliva. sTNFRII and sIgA levels were determined in saliva samples by ELISA from healthy people and patients with dementia in GDS stages 5–7. The concentrations of these markers were also correlated with the GDS stage and sex. We observed a significant decrease (*** p ≤ 0.001) in the levels of sTNFRII (pg/mL) and a significant increase (** p ≤ 0.01) in the levels of sIgA (ng/mL) in the saliva of patients with dementia compared to the healthy control group. We did not observe a correlation with the data of the biomarkers regarding the GDS stage and sex. The results obtained for sTNFRII are consistent with those obtained by other authors on brain tissue, who conclude that unopposed neuronal TNFRI signaling, when TNFRII is selectively downregulated, leads to a more severe course of AD pathogenesis. Regarding sIgA, the elevated values of sIgA may reflect the immune status of these patients. Therefore, these biomarkers can provide us with relevant information through a non-invasive method such as saliva analysis. [ABSTRACT FROM AUTHOR]

K. pneumoniae is one of the leading microorganisms causing nosocomial infections among premature newborns. The ineffectiveness of immune defense, morphofunctional immaturity, length of hospitalization and invasive procedures create the prerequisites for the implementation of the infectious process in a hospital setting. The question of the reasons for the development of infection, the etiological agent of which colonizes the intestines, remains open. Purpose of the study: to evaluate the expression of CD14+CD282+, CD14+CD284+, CD14+HLA-DR+, and CD14+CD11b+ receptors on blood monocytes and the level of sIgA in coprofiltrates in premature infants with intestinal colonization by K. pneumonia with different genetic profiles. We examined 11 children with the uge gene (group 1), 20 newborns with the uge + fim genes (group 2), and 12 children with the kfu + uge + fim genes. Microbiological examination of feces included identification and antibiotic sensitivity of microorganisms. Detection of the uge, fim and kfu genes in K. pneumoniae strains was carried out by PCR. The expression level of monocyte activation markers was determined by flow cytometry. Gestational age and anthropometric parameters did not differ between newborns. Children identified with the fim gene in combination with other genes were more often discharged home with K. pneumoniae than with the uge gene. In these children, a decrease in the level of expression of CD14+CD282+, CD14+CD284+, CD14+CD11b+, CD14+HLA-DR+ receptors at birth and upon reaching postconceptional age, and a low sIgA content in coprofiltrates during 24 days of life were recorded. Thus, a decrease in the expression of CD14+CD282+, CD14+CD284+, CD14+CD282+ and CD14+HLA-DR+ receptors by blood monocytes and insufficiency of sIgA production in the large intestine determine a long period of colonization of K. pneumoniae strains with the presence of the fim gene in combination with other genes (from 15 to 180 days), as well as the possibility of Klebsiella infection occurring in subsequent periods of the child’s life. Much more often, children with the combination of genes uge + fim and kfu + uge + fim were discharged from the hospital with a diagnosis of anemia; only in these groups of children was the development of bronchopulmonary dysplasia recorded.

Abstract Mucosal immunity plays a major role not only in the prevention but probably also in the outcomes of COVID-19. An enhanced production of secretory immunoglobulin A (sIgA) might contribute to the activation of the immune response mechanisms. To assess the levels of sIgA produced by epithelial cells in the nasal and pharyngeal mucosa and those measured in salivary gland secretions and to study the course of COVID-19 following the combined scheme of intranasal and subcutaneous administration of a bacteria-based immunostimulant agent. This study included 69 patients, aged between 18 and 60, who had moderate COVID-19 infection. They were divided into two groups: Group 1 (control group) included 39 patients who received only background therapy, and Group 2 was made up of 30 patients who received background therapy in combination with the Immunovac VP4 vaccine, a bacteria-based immunostimulant agent, which was given for 11 days starting from the day of admission to hospital. The levels of sIgA were measured by ELISA in epithelial, nasal and pharyngeal swabs, and salivary gland secretions at baseline and on days 14 and 30. The combined scheme of intranasal and subcutaneous administration of the Immunovac VP4 vaccine in the complex therapy of patients with COVID-19 is accompanied by increased synthesis of sIgA in nasal and pharyngeal swabs, more intense decrease in the level of C-reactive protein (CRP) and reduction in the duration of fever and length of hospitalization compared to the control group. Prescribing a immunostimulant agent containing bacterial ligands in complex therapy for COVID-19 patients helps to enhance mucosal immunity and improves the course of the disease.

Background: Pandan Anggur plant is an endemic plant of the Papua archipelago in Indonesia, and the fruit called Pandan Anggur Fruit (PAF) is freshly consumed or prepared as a juice. Based on previous studies on the phytochemical content of PAF, the ethanol and water extract contain flavonoids, which act as immunomodulators, to regulate the response of immunity. Objectives: This study aimed to examine the potential of PAF as an immunomodulator in malnutrition cases, by evaluating six parameters which are phagocytosis capacity and nitric oxide (NO) production of peritoneal macrophage, spleen lymphocyte proliferation, IFN-γ and IL-4 in lymphocyte culture, and intestinal sIgA levels. By proving the potential of PAF as an immunomodulator, this research will lead to significant development of functional food products of Pandan Anggur. Methods: A total of 35 Sprague Dawley rats were used as animal models divided into seven different groups named standard group (healthy standard), malnourished (negative control), malnourished rats given Imboost Force (positive control), as well as PAF ethanol extract doses of I, II, III, and PAF water extract. The treatment lasted for seven weeks in total and the measurement of immunomodulator parameters was carried out at the end of the treatment period. The immunomodulator parameters included phagocytosis capacity and nitric oxide (NO) production of peritoneal macrophage, spleen lymphocyte proliferation, IFN-γ and IL-4 in lymphocyte culture, and intestinal sIgA levels. Result: The results indicated that the administration of PAF ethanol extract at a dose of 3.15 mg/mL provided an optimum immunostimulant effect, by increasing the macrophage phagocytosis capacity, nitric oxide, lymphocyte proliferation, IL-4, and sIgA levels in rat intestine. However, increasing the dose of extract did not produce a better effect, but led to suppression of immunity. Conclusion: PAF extract at a dose of 3.15 mg/mL provides an immunostimulant effect. [ABSTRACT FROM AUTHOR]

The treatment and prevention of pathogenic diseases by lactic acid bacteria (LAB) has attracted more and more attention. As a special LAB, Levilactobacillus brevis (L. brevis) has relatively less research on its antibacterial infection in vivo, and its protective effect and mechanism still need to be fully studied. In this study, we selected L. brevis 23017, which can regulate the intestinal immunity of the host animal and resist pathogen infection, to evaluate its protective role and potential molecular mechanisms in the mouse model of S. typhimurium C7731 infection. As expected, we confirmed that L. brevis 23017 reduced the diarrhea rate and increased the daily weight gain and survival rate of the mouse model, and inhibited S. typhimurium colonization in the jejunum and liver. It also reduced the level of oxidative damage and protected the integrity of intestinal tissue by increasing the activity of intestinal antioxidant enzymes (SOD, GSH-Px and T-AOC). From the perspective of intestinal mucosal barrier injury and repair, it was confirmed that L. brevis 23017 could increase the expression levels of intestinal tight junction proteins (ZO-1 and OCLN). Our research results also show that L. brevis 23017 inhibits the inflammatory response and promotes the occurrence of cellular immunity in the body by promoting the increase in IL-10 and inhibiting IL-13 in serum and intestinal tissue. Notably, L. brevis 23017 increased total secretory immunoglobulin A (SIgA) levels in the intestine, which were closely associated with elevated levels of IL-5, IL-13, pIgR, j-chain, and IgAα-chain. In addition, L. brevis 23017 increased the expression of antioxidant proteins Nrf2, NQO1, and HO-1 associated with Nrf2 signaling to inhibit intestinal oxidative damage. This mechanism may be responsible for its protective effect against S. typhimurium-infected intestine. Our study provides new evidence and theoretical support for the analysis of the anti-bacterial infection effect and mechanism of L. brevis, which will contribute to the development of L. brevis and the treatment of pathogenic bacteria intestinal infection. [ABSTRACT FROM AUTHOR]

The Slovenian climate has undergone significant fluctuations, and an understanding of the past climate is necessary to improve models and recognise long-term patterns. The cryosphere environment, such as ice core samples, provides valuable palaeoclimate data. Palynology and dendroclimatology are also effective ways to study long-term changes in vegetation and reconstruct past climates using pollen and tree proxies. Sediment cores from various locations in Slovenia have been studied to understand past environmental changes. Borehole temperature profiles as well as historical records were also used to reconstruct past climate conditions. Studies have shown specific periods when climatic changes likely played a major role, but a complete timeline of the Slovenian climate throughout the Holocene has not yet been fully developed. [ABSTRACT FROM AUTHOR]

Background: The most widely used vaccination against SARS-associated coronavirus (SARS-CoV-2) is the Pfizer vaccine, which provides protection against this virus. However, its ability to safeguard the oral cavity is unclear, and neither are the exact immunological biomarker levels it activates. This study aims to detect if the Pfizer-BionTech covid-19 vaccine protects the oral cavity after vaccination by estimating the salivary sIgA levels, IL-21 in saliva for subjects before and after vaccination with the Pfizer covid-19 vaccine. Methods: In this cross-sectional study, 70 subjects were followed up: the non-vaccinated individuals served as the control group, and those who received the first and second doses of the vaccine constituted the study group. The salivary biomarkers sIgA and IL-21 were detected using enzyme-linked immunosorbent assay (ELISA) kits. Results: The current study showed a highly significant (p=0.0001) in secretary-IgA levels after the first vaccination in follow-up compared with non-vaccinated in same subjects (as control), while a non-significant when compared with after second vaccination groups. However, salivary IL-21 levels showed highly significant differences between the non-vaccinated follow-up comparing with after first and after second vaccination also compared the first with second followed up groups reflect an increased and highly significant difference (p

ABSTRACTVaccination strategies that can induce a broad spectrum immune response are important to enhance protection against SARS-CoV-2 variants. We conducted a randomized, double-blind and parallel controlled trial to evaluate the safety and immunogenicity of the bivalent (5×1010viral particles) and B.1.1.529 variant (5×1010viral particles) adenovirus type-5 (Ad5) vectored COVID-19 vaccines administrated via inhalation. 451 eligible subjects aged 18 years and older who had been vaccinated with three doses inactivated COVID-19 vaccines were randomly assigned to inhale one dose of either B.1.1.529 variant Ad5 vectored COVID-19 vaccine (Ad5-nCoVO-IH group, N=150), bivalent Ad5 vectored COVID-19 vaccine (Ad5-nCoV/O-IH group, N=151), or Ad5 vectored COVID-19 vaccine (5×1010viral particles; Ad5-nCoV-IH group, N=150). Adverse reactions reported by 37 (24.67%) participants in the Ad5-nCoVO-IH group, 28 (18.54%) in the Ad5-nCoV/O-IH group, and 26 (17.33%) in the Ad5-nCoV-IH group with mainly mild to moderate dry mouth, oropharyngeal pain, headache, myalgia, cough, fever and fatigue. No serious adverse events related to the vaccine were reported. Investigational vaccines were immunogenic, with significant difference in the GMTs of neutralizing antibodies against Omicron BA.1 between Ad5-nCoV/O-IH (43.70) and Ad5-nCoV-IH (29.25) at 28 days after vaccination (P=0.0238). The seroconversion rates of neutralizing antibodies against BA.1 in Ad5-nCoVO-IH, Ad5-nCoV/O-IH, and Ad5-nCoV-IH groups were 56.00%, 59.60% and 48.67% with no significant difference among the groups. Overall, the investigational vaccines were demonstrated to be safe and well tolerated in adults, and was highly effective in inducing mucosal immunities in addition to humoral and cellular immune responses defending against SARS-CoV-2 variants.Trial registration: Chictr.org identifier: ChiCTR2200063996.

This study aimed to compare salivary characteristics between SECC and caries free children. It is an analytic study with cross-sectional design. 52 children aged 10-27 months comprised 26 SECC children and 26 caries free children. The subject selection’s technique was purposive sampling from the Johor districts, Medan-Indonesia public health center. SECC characteristics were based on AAPD. Examination of flow rate, pH and salivary buffer capacity were using GC Saliva Check Buffer. sIgA and lysozyme level were examined using the ELISA method using a microplate reader. Examination of lysozyme activities used lysozyme detection kit and read by spectrophotometer. The data were analyzed using the Mann-Whitney test, Chi-Square, and Spearman correlation. The result showed that children with SECC had lower lysozyme level, salivary flow, pH and buffer capacity than caries free children (p<0.05). There were correlations among lysozyme level, salivary flow, pH and buffer capacity to deft index (p<0.05). It was concluded that SECC children had poorer salivary characteristics than caries free children, thus facilitating the development of dental caries. [ABSTRACT FROM AUTHOR]

The yak has a unique physiological structure suited to life in anoxic and cold environments at high altitudes. The aim of this study was to isolate Bacillus species with good probiotic properties from yak feces. A series of tests were performed on the isolated Bacillus: 16S rRNA identification, antibacterial activity, tolerance to gastroenteric fluid, hydrophobicity, auto-aggregation, antibiotic sensitivity, growth performance, antioxidants, and immune indexes. A safe and harmless Bacillus pumilus DX24 strain with good survival rate, hydrophobicity, auto-aggregation, and antibacterial activity was identified in the yak feces. Feeding mice with Bacillus pumilus DX24 increased their daily weight gain, jejunal villus length, villi/Crypt ratio, blood IgG levels, and jejunum sIgA levels. This study confirmed the probiotic effects of Bacillus pumilus isolated from yak feces and provides the theoretical basis for the clinical application and development of new feed additives. [ABSTRACT FROM AUTHOR]

(1) The aim of the study was to analyze the salivary concentrations of lysozyme, lactoferrin, and sIgA antibodies in adult patients in the late period after allogeneic stem cell transplantation (alloHSCT). The relationship between these concentrations and the salivary secretion rate and the time elapsed after alloHSCT was investigated. The relationship between the concentrations of lysozyme, lactoferrin, and sIgA and the titer of the cariogenic bacteria S. mutans and L. acidophilus was assessed. (2) The study included 54 individuals, aged 19 to 67 (SD = 40.06 ± 11.82; Me = 39.5), who were 3 to 96 months after alloHSCT. The concentrations of lysozyme, lactoferrin, and sIgA were assessed in mixed whole resting saliva (WRS) and mixed whole stimulated saliva (WSS). (3) The majority of patients had very low or low concentrations of the studied salivary components (WRS—lysozyme: 52, lactoferrin: 36, sIgA: 49 patients; WSS—lysozyme: 51, lactoferrin: 25, sIgA: 51 patients). The levels of lactoferrin in both WRS and WSS were statistically significantly higher in the alloHSCT group than in the control group (CG) (alloHSCT patients—WRS: M = 40.18 μg/mL; WSS: M = 27.33 μg/mL; CG—WRS: M = 17.58 μg/mL; WSS: 10.69 μg/mL). No statistically significant correlations were observed between lysozyme, lactoferrin, and sIgA concentrations and the time after alloHSCT. In the group of patients after alloHSCT a negative correlation was found between the resting salivary flow rate and the concentration of lactoferrin and sIgA. The stimulated salivary flow rate correlated negatively with lactoferrin and sIgA concentrations. Additionally, the number of S. mutans colonies correlated positively with the concentration of lysozyme and sIgA. (4) The concentrations of non-specific and specific immunological factors in the saliva of patients after alloHSCT may differ when compared to healthy adults; however, the abovementioned differences did not change with the time after transplantation. [ABSTRACT FROM AUTHOR]

Background: The most widely used vaccination against SARS-associated coronavirus (SARS-CoV-2) is the Pfizer vaccine, which provides protection against this virus. However, its ability to safeguard the oral cavity is unclear, and neither are the exact immunological biomarker levels it activates. This study aims to detect if the Pfizer-BionTech covid-19 vaccine protects the oral cavity after vaccination by estimating the salivary sIgA levels, IL-21 in saliva for subjects before and after vaccination with the Pfizer covid-19 vaccine. Methods: In this cross-sectional study, 70 subjects were followed up: the non-vaccinated individuals served as the control group, and those who received the first and second doses of the vaccine constituted the study group. The salivary biomarkers sIgA and IL-21 were detected using enzyme-linked immunosorbent assay (ELISA) kits. Results: The current study showed a highly significant (p=0.0001) in secretary-IgA levels after the first vaccination in follow-up compared with non-vaccinated in same subjects (as control), while a non-significant when compared with after second vaccination groups. However, salivary IL-21 levels showed highly significant differences between the nonvaccinated follow-up comparing with after first and after second vaccination also compared the first with second followed up groups reflect an increased and highly significant difference (p<0.001). Conclusion: The current study shows that the Pfizer vaccine has a minimal impact on sIgA levels due to its primary role in systemic rather than local salivary protection. However, a rise in IL-21 was observed after the first dose in noninfected participants, indicating its systemic protective effectiveness, which stabilizes after the second dose. [ABSTRACT FROM AUTHOR]

Lactobacilli have played an important role in the gut health of pets. The aim of this research was to study the effects of isolated Lactobacilli (named L11) on the immune, nutrient metabolism, and gut health of cats. Twelve healthy adult cats were randomly assigned into two groups, the control group (CONTROL, n = 6, without any probiotics product) and the treatment group (probiotics, n = 6, L11 109 CFU/kg feed), while using the same dry diet. On day 28, blood and fecal samples were collected, and the blood biochemical indices, fecal microbiota, short-chain fatty acids (SCFAs), immunological parameters, and odorous substances were separately tested. The triglyceride of the blood was decreased after using L11 (p < 0.05), which could probably alleviate the occurrence of cat obesity to some extent. The sIgA of the feces was increased by 30.1% (p < 0.05), which could enhance the cat's immunity. The abundance of Bifidobacteria was increased after using L11 (p < 0.05), and the indole and 3-methylindole of the feces were both reduced compared with the control group; 3-methylindole was especially reduced by 67.3% (p < 0.05), which showed that L11 could also improve the intestinal state of cats. Therefore, this research shows that L11 could be a good choice to improve the gut health and immune functions of cats, and it is probably related to the lipid mechanism of cats. [ABSTRACT FROM AUTHOR]

Mucosal vaccines protect against respiratory virus infection by stimulating the production of IgA antibodies that protect against virus invasion of the mucosal epithelium. In this study, a novel protein subunit mucosal vaccine was constructed for protection against infection by the beta coronavirus SARS-CoV-2. The vaccine was assembled by linking a gene encoding the SARS-CoV-2 virus S1 angiotensin converting enzyme receptor binding domain (ACE-2-RBD) downstream from a DNA fragment encoding the cholera toxin B subunit (CTB), a mucosal adjuvant known to stimulate vaccine immunogenicity. A 42 kDa vaccine fusion protein was identified in homogenates of transformed E. coli BL-21 cells by acrylamide gel electrophoresis and by immunoblotting against anti-CTB and anti-ACE-2-RBD primary antibodies. The chimeric CTB-SARS-CoV-2-ACE-2-RBD vaccine fusion protein was partially purified from clarified bacterial homogenates by nickel affinity column chromatography. Further vaccine purification was accomplished by polyacrylamide gel electrophoresis and electro-elution of the 42 kDa chimeric vaccine protein. Vaccine protection against SARS-CoV-2 infection was assessed by oral, nasal, and parenteral immunization of BALB/c mice with the CTB-SARS-CoV-2-ACE-2-RBD protein. Vaccine-induced SARS-CoV-2 specific antibodies were quantified in immunized mouse serum by ELISA analysis. Serum from immunized mice contained IgG and IgA antibodies that neutralized SARS-CoV-2 infection in Vero E6 cell cultures. In contrast to unimmunized mice, cytological examination of cell necrosis in lung tissues excised from immunized mice revealed no detectable cellular abnormalities. Mouse behavior following vaccine immunization remained normal throughout the duration of the experiments. Together, our data show that a CTB-adjuvant-stimulated CTB-SARS-CoV-2-ACE-2-RBD chimeric mucosal vaccine protein synthesized in bacteria can produce durable and persistent IgA antibodies in mice that neutralize the SARS-CoV-2 subvariant Omicron BA.1.1. [ABSTRACT FROM AUTHOR]

ABSTRACT: The avian influenza virus is infected through the mucosal route, thus mucosal barrier defense is very important. While the inactivated H9N2 vaccine cannot achieve sufficient mucosal immunity, adjuvants are needed to induce mucosal and systemic immunity to prevent poultry from H9N2 influenza virus infection. Our previous study found that polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) had immune-enhancing effects in vitro. This study aimed to evaluate the mucosal immune responses of oral whole-inactivated H9N2 virus (WIV)+AMP-ZnONPs and its impact on the animal challenge protection, and the corresponding changes of pulmonary metabolomics after the second immunization. The results showed that compared to the WIV, the combined treatment of WIV and AMP-ZnONPs significantly enhanced the HI titer, IgG and specific sIgA levels, the number of goblet cells and intestinal epithelial lymphocytes (iIELs) as well as the expression of J-chain, polymeric immunoglobulin receptor (pIgR), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β). In viral attack experiments, WIV combing with AMP-ZnONPs effectively reduced lung damage and viral titers in throat swabs. Interestingly, significant changes of both the IgA intestinal immune network and PPAR pathway could also be found in the WIV+AMP-ZnONPs group compared to the non-infected group. Taken together, these findings suggest that AMP-ZnONPs can serve as a potential mucosal vaccine adjuvant, thereby avoiding adverse stress and corresponding costs caused by vaccine injection.

The oral and nasal cavities are covered by the mucosal epithelium that starts at the beginning of the aero-digestive tract. These mucosal surfaces are continuously exposed to environmental antigens including pathogens and allergens and are thus equipped with a mucosal immune system that mediates initial recognition of pathogenicity and initiates pathogen-specific immune responses. At the dawn of our scientific effort to explore the mucosal immune system, dental science was one of the major driving forces as it provided insights into the importance of mucosal immunity and its application for the control of oral infectious diseases. The development of mucosal vaccines for the prevention of dental caries was thus part of a novel approach that contributed to building the scientific foundations of the mucosal immune system. Since then, mucosal immunology and vaccines have gone on a scientific journey to become one of the major entities within the discipline of immunology. Here, we introduce our past and current efforts and future directions for the development of mucosal vaccines, specifically a rice-based oral vaccine (MucoRice) and a nanogel-based nasal vaccine, with the aim of preventing and controlling gastrointestinal and respiratory infectious diseases using the interdisciplinary fusion of mucosal immunology with agricultural science and biomaterial engineering, respectively.

The treatment and prevention of pathogenic diseases by lactic acid bacteria (LAB) has attracted more and more attention. As a special LAB, Levilactobacillus brevis (L. brevis) has relatively less research on its antibacterial infection in vivo, and its protective effect and mechanism still need to be fully studied. In this study, we selected L. brevis 23017, which can regulate the intestinal immunity of the host animal and resist pathogen infection, to evaluate its protective role and potential molecular mechanisms in the mouse model of S. typhimurium C7731 infection. As expected, we confirmed that L. brevis 23017 reduced the diarrhea rate and increased the daily weight gain and survival rate of the mouse model, and inhibited S. typhimurium colonization in the jejunum and liver. It also reduced the level of oxidative damage and protected the integrity of intestinal tissue by increasing the activity of intestinal antioxidant enzymes (SOD, GSH-Px and T-AOC). From the perspective of intestinal mucosal barrier injury and repair, it was confirmed that L. brevis 23017 could increase the expression levels of intestinal tight junction proteins (ZO-1 and OCLN). Our research results also show that L. brevis 23017 inhibits the inflammatory response and promotes the occurrence of cellular immunity in the body by promoting the increase in IL-10 and inhibiting IL-13 in serum and intestinal tissue. Notably, L. brevis 23017 increased total secretory immunoglobulin A (SIgA) levels in the intestine, which were closely associated with elevated levels of IL-5, IL-13, pIgR, j-chain, and IgAα-chain. In addition, L. brevis 23017 increased the expression of antioxidant proteins Nrf2, NQO1, and HO-1 associated with Nrf2 signaling to inhibit intestinal oxidative damage. This mechanism may be responsible for its protective effect against S. typhimurium-infected intestine. Our study provides new evidence and theoretical support for the analysis of the anti-bacterial infection effect and mechanism of L. brevis, which will contribute to the development of L. brevis and the treatment of pathogenic bacteria intestinal infection.

Background: Although extensive research has been conducted on the role of local immunity in patients with SARS-CoV-2, little is known about the production and concentrations of secretory IgA (SIgA) in different mucosal compartments. This article aims to assess the secretion of SIgA in the nasal and pharyngeal compartments and saliva of patients with COVID-19 and to investigate the possibility and efficiency of correction of their secretion using combined intranasal and oral administration of a pharmaceutical containing antigens of opportunistic microorganisms. Methods: This study included 78 inpatients, aged between 18 and 60 years, who had confirmed COVID-19 with moderate lung involvement. The control group (n=45) received basic therapy, and the treatment group (n=33) was additionally administered the bacteria-based pharmaceutical Immunovac VP4 from day 1 to day 10 of hospitalization. SIgA levels were measured by ELISA at baseline and on days 14 and 30. Results: No systemic or local reactions associated with Immunovac VP4 were reported. We observed a statistically significant reduction in the duration of fever and hospitalization in patients who received Immunovac VP4 compared with those from the control group (p=0.03 and p=0.05, respectively). Changes over time in SIgA levels in nasal swabs were found to be significantly different in the two treatment groups (F=7.9, p[78.0]

ABSTRACTCoronavirus disease 2019 (COVID-19) vaccines have saved millions of lives. However, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged causing large numbers of breakthrough infections. These developments necessitated the rollout of COVID-19 vaccine booster doses. It has been reported that mucosal antibody levels in the upper respiratory tract, especially for secretory IgA (sIgA), correlate with protection from infection with SARS-CoV-2. However, it is still unclear how high levels of mucosal antibodies can be induced. In this study, we measured serum IgG, saliva IgG, and saliva sIgA responses in individuals who received COVID-19 mRNA booster vaccinations or who experienced breakthrough infections. We found that mRNA booster doses could induce robust serum and saliva IgG responses, especially in individuals who had not experienced infections before, but saliva sIgA responses were weak. In contrast, breakthrough infections in individuals who had received the primary mRNA vaccination series induced robust serum and saliva IgG as well as saliva sIgA responses. Individuals who had received a booster dose and then had a breakthrough infection showed low IgG induction in serum and saliva but still responded with robust saliva sIgA induction. These data suggest that upper respiratory tract exposure to antigen is an efficient way of inducing mucosal sIgA while exposure via intramuscular injection is not.IMPORTANCEAntibodies on mucosal surfaces of the upper respiratory tract have been shown to be important for protection from infection with SARS-CoV-2. Here we investigate the induction of serum IgG, saliva IgG, and saliva sIgA after COVID-19 mRNA booster vaccination or breakthrough infections.

The oral cavity is home to the second most diverse microbiome in the human body. This community contributes to both oral and systemic health. Acquisition and development of the oral microbiome is a dynamic process that occurs over early life; however, data regarding longitudinal assembly of the infant oral microbiome is scarce. While numerous factors have been associated with the composition of the infant oral microbiome, early feeding practices (breastfeeding and the introduction of solids) appear to be the strongest determinants of the infant oral microbiome. In the present review, we draw together data on the maternal, infant, and environmental factors linked to the composition of the infant oral microbiome, with a focus on early nutrition. Given evidence that breastfeeding powerfully shapes the infant oral microbiome, the review explores potential mechanisms through which human milk components, including microbes, metabolites, oligosaccharides, and antimicrobial proteins, may interact with and shape the infant oral microbiome. Infancy is a unique period for the oral microbiome. By enhancing our understanding of oral microbiome assembly in early life, we may better support both oral and systemic health throughout the lifespan. [ABSTRACT FROM AUTHOR]

Gut microbiota (GM) is essential for host health, and changes in the GM are related to the development of various diseases. Recently, secretory immunoglobulin A (SIgA), the most abundant immunoglobulin isotype in the intestinal mucosa, has been found to play an essential role in controlling GM. SIgA dysfunction can lead to changes in the GM and is associated with the development of various GM-related diseases. Although in early stage, recent studies have shown that assorted dietary interventions, including vitamins, amino acids, fatty acids, polyphenols, oligo/polysaccharides, and probiotics, can influence the intestinal SIgA response and SIgA-GM interaction. Dietary intervention can enhance the SIgA response by directly regulating it (from top to bottom) or by regulating the GM structure or gene expression (from bottom to top). Furthermore, intensive studies involving the particular influence of dietary intervention on SIgA-binding to the GM and SIgA repertoire and the precise regulation of the SIgA response via dietary intervention are still exceedingly scarce and merit further consideration. This review summarizes the existing knowledge and (possible) mechanisms of the influence of dietary intervention on the SIgA-GM interaction. Key issues are considered, and the approaches in addressing these issues in future studies are also discussed. [ABSTRACT FROM AUTHOR]

Latar belakang. Kolostrum susu sapi atau Bovine colostrum mengandung berbagai growth factor dan immune factor, salah satunya secretory IgA (sIgA) yang dengan jumlah signifikan dapat menghalangi adhesi patogen ke membrane mukosa dan menghambat kolonisasi sehingga bermanfaat untuk mengobati penyakit di saluran pencernaan. Penelitian yang telah dilakukan di Indonesia belum banyak membahas secara spesifik hubungan sIgA yang didapatkan dari kolostrum susu sapi sebagai terapi tambahan diare akut pada anak. Tujuan. Mengetahui pengaruh pemberian kolostrum susu sapi terhadap durasi diare akut dehidrasi ringan sedang dan kadar sekretori IgA pada anak Metode. Penelitian eksperimental yang dilaksanakan di Puskesmas dan Rumah Sakit di kota Padang. Penelitian dimulai dari bulan februari tahun 2022 sampai November 2022. Data terkumpul 30 sampel masing-masing pada kelompok kontrol yang mendapatkan terapi standar WHO dan kelompok intervensi yang mendapatkan terapi standar who ditambah kolostrum susu sapi. Dilakukan pengamatan terhadap durasi diare akut serta pemeriksaan terhadap kadar sIgA. Hasil. Terjadi pemendekan durasi diare secara signifikan antara kelompok intervensi dan kelompok kontrol sebesar 11,93 jam (p=0,021). Terdapat perbedaan kadar sIgA yang signifikan antara sebelum dan sesudah pemberian kolostrum susu sapi pada kelompok intervensi (p=0,003). Kesimpulan. Pemberian kolostrum susu sapi dapat memperpendek rerata durasi diare akut dan meningkatkan rerata kadar sIgA secara bermakna. Pemberian kolostrum susu sapi ini dapat disarankan sebagai terapi adjuvan dalam tatalaksana diare akut pada anak.

Copyright of Dergiabant is the property of Dergiabant and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Donor human milk (DHM) is the second-best nutrition for preterm infants when their own mother's milk is unavailable. The nutrient content of human milk is influenced by various factors, including gestational and postpartum age, but there are no data regarding DHM composition in Japan. The aim of this study was to determine the protein and immune component content of DHM in Japan and to elucidate the effects of gestational and postpartum age on nutrient composition. From September 2021 to May 2022, 134 DHM samples were collected from 92 mothers of preterm and term infants. Protein concentrations in preterm DHM (n = 41) and term DHM (n = 93) were analyzed using a Miris Human Milk Analyzer. The concentrations of secretory immunoglobulin A (sIgA) and lactoferrin, major immune components, were measured using enzyme-linked immunosorbent assays. Preterm DHM exhibited higher protein content than term DHM (1.2 g/dL and 1.0 g/dL, respectively, p < 0.001), whereas sIgA content was higher in term DHM than in preterm DHM (110 μg/mL and 68.4 μg/mL, respectively, p < 0.001). Gestational age was negatively correlated with protein levels and positively correlated with sIgA and lactoferrin levels. Furthermore, a negative correlation was found between postpartum week and protein, sIgA, and lactoferrin concentrations. Our data suggest that gestational and postpartum age affects protein, sIgA, and lactoferrin concentrations in DHM. These results indicate the importance of nutritional analysis for the appropriate use of DHM in preterm infants. [ABSTRACT FROM AUTHOR]

The post-COVID-19 recovery period is characterized by persistence of some symptoms, with immunological alterations being of great importance. Development of preventive measures to normalize mucosal immunity after a coronavirus infection determines the relevance of the current study. The aim was to study dynamics of clinical symptoms and level of secretory immunoglobulin A in individuals after a novel coronavirus infection as well as evaluate effectiveness of using IFNa-2b. Materials and methods. A study was conducted with patients aged 18 to 60 years old (n = 130), surveyed 1 to 9 months after post-infection, as well as in apparently healthy individuals lacking COVID-19 (n = 15). Previous novel coronavirus infection and post-COVID manifestations were verified based on medical documentation, complaints, anamnesis data, physical examination and questionnaires. The concentration of salivatory and nasopharyngeal mucosal sIgA was measured dynamically prior to and after administration of local therapy with IFNa-2b (gel applied intranasally twice a day for 30 days). Results. The acute period of COVID-19 was characterized by fever, anosmia, severe asthenia (fatigue and weakness), muscle and joint pain. Among the post-COVID manifestations at early period (13 months), pain in the joints and muscles (75.0%) as well as elevated body temperature (21.2%) were reliably detected, whereas in the long period (69 months) there were revealed dominance with the same frequency of shortness of breath, muscle and joint pain (75.8%, respectively). Based on examination data in healthy subjects, there was determined an arbitrary normal range of secretory IgA in saliva 6.451.81 mg/ml and nasal swabs 13.433.24 mg/ml. In the group of patients 13 months post-infection, therapy with IFNa-2b one month later resulted in significantly increased level of secretory IgA in saliva (from 1.840.28 to 5.781.96 mg/ml) and in nasal swabs (from 28.613.0 to 39.833.85 mg/ml) by more than 3- and 1.5-fold, respectively. In the group of patients without therapy was featured with stably sustained decline in sIgA level up to 9 months after COVID-19. In particular, the level of saliva sIgA ranged from 2.360.56 down to 2.160.66 mg/ml, and in nasal smears from 15.661.32 to 10.231.07 mg/ml that differed insignificantly compared to baseline level. The rate of respiratory diseases prevailed in this group (27.6% of cases), which fully lacked in the group of topically administered IFNa-2b. Conclusion. In the post-COVID period, multiple organ disorders persist and reduced sIgA level is registered. Intranasally applied IFNa-2b made possible to normalize sIgA level and prevent accumulation of respiratory infectious pathologies.

In structural design standards, loads are often assumed to be random quantities to give load factors. This study deals with the Stochastic Isogeometric Analysis (SIGA) for a Functionally Graded Plate (FGP) subjected to random distribution loads. The spatial random variation of distribution loads is modeled as a homogeneous Gaussian random field in the plane of the functionally graded plate. The governing equation of the functional grade plate is derived using the NURBS-based isogeometric analysis and the refined plate theory. SIGA is developed based on standard NURBS-based isogeometric analysis in conjunction with the first-order perturbation expansions of random loads. This approach was verified with Monte Carlo simulation, and the numerical results showed the effect of random loads on the variation of displacements and stresses of the functionally graded plate. [ABSTRACT FROM AUTHOR]

Inflammatory lung diseases represent a persistent burden for patients and the global healthcare system. The combination of high morbidity, (partially) high mortality and limited innovations in the last decades, have resulted in a great demand for new therapeutics. Are therapeutic IgA antibodies possibly a new hope in the treatment of inflammatory lung diseases? Current research increasingly unravels the elementary functions of IgA as protector against infections and as modulator of overwhelming inflammation. With a focus on IgA, this review describes the pathological alterations in mucosal immunity and how they contribute to chronic inflammation in the most common inflammatory lung diseases. The current knowledge of IgA functions in the circulation, and particularly in the respiratory mucosa, are summarized. The interplay between neutrophils and IgA seems to be key in control of inflammation. In addition, the hurdles and benefits of therapeutic IgA antibodies, as well as the currently known clinically used IgA preparations are described. The data highlighted here, together with upcoming research strategies aiming at circumventing the current pitfalls in IgA research may pave the way for this promising antibody class in the application of inflammatory lung diseases. [ABSTRACT FROM AUTHOR]

Given the high prevalence of intestinal disease in humans and animals, there is a strong need for clinically relevant models recapitulating gastrointestinal systems, ideally replacing in vivo models in accordance with the principles of the 3R. We established a canine organoid system and analysed the neutralising effects of recombinant versus natural antibodies on Clostridioides difficile toxins A and B in this in vitro system. Sulforhodamine B cytotoxicity assays in 2D and FITC-dextran barrier integrity assays on basal-out and apical-out organoids revealed that recombinant, but not natural antibodies, effectively neutralised C. difficile toxins. Our findings emphasise that canine intestinal organoids can be used to test different components and suggest that they can be further refined to also mirror complex interactions between the intestinal epithelium and other cells. [ABSTRACT FROM AUTHOR]

How gut immunity in early life is shaped by birth in relation to delivery mode, intrapartum antibiotic prophylaxis (IAP) and labor remains undetermined. We aimed to address this gap with a study of secretory Immunoglobulin A (SIgA) in the infant gut that also tested SIgA-stimulating pathways mediated by gut microbiota and metabolites. Among 1017 Canadian full-term infants, gut microbiota of fecal samples collected at 3 and 12 months were profiled using 16S rRNA sequencing; C. difficile was quantified by qPCR; fecal metabolites and SIgA levels were measured by NMR and SIgA enzyme-linked immunosorbent assay, respectively. We assessed the putative causal relationships from birth events to gut microbiota and metabolites, and ultimately to SIgA, in statistical sequential mediation models, adjusted for maternal gravida status in 551 infants. As birth mode influences the ability to breastfeed, the statistical mediating role of breastfeeding status and milk metabolites was also evaluated. Relative to vaginal birth without maternal IAP, cesarean section (CS) after labor was associated with reduced infant gut SIgA levels at 3 months (6.27 vs. 4.85 mg/g feces, p < 0.05); this association was sequentially mediated through gut microbiota and metabolites of microbial or milk origin. Mediating gut microbiota included Enterobacteriaceae, C. difficile, and Streptococcus. The milk or microbial metabolites in CS-SIgA mediating pathways were galactose, fucose, GABA, choline, lactate, pyruvate and 1,2-propanediol. This cohort study documented the impact of birth on infant gut mucosal SIgA. It is the first to characterize gut microbe-metabolite mediated pathways for early-life SIgA maturation, pathways that require experimental verification. [ABSTRACT FROM AUTHOR]

(1) The aim of the study was to analyze the salivary concentrations of lysozyme, lactoferrin, and sIgA antibodies in adult patients in the late period after allogeneic stem cell transplantation (alloHSCT). The relationship between these concentrations and the salivary secretion rate and the time elapsed after alloHSCT was investigated. The relationship between the concentrations of lysozyme, lactoferrin, and sIgA and the titer of the cariogenic bacteria S. mutans and L. acidophilus was assessed. (2) The study included 54 individuals, aged 19 to 67 (SD = 40.06 ± 11.82; Me = 39.5), who were 3 to 96 months after alloHSCT. The concentrations of lysozyme, lactoferrin, and sIgA were assessed in mixed whole resting saliva (WRS) and mixed whole stimulated saliva (WSS). (3) The majority of patients had very low or low concentrations of the studied salivary components (WRS—lysozyme: 52, lactoferrin: 36, sIgA: 49 patients; WSS—lysozyme: 51, lactoferrin: 25, sIgA: 51 patients). The levels of lactoferrin in both WRS and WSS were statistically significantly higher in the alloHSCT group than in the control group (CG) (alloHSCT patients—WRS: M = 40.18 μg/mL; WSS: M = 27.33 μg/mL; CG—WRS: M = 17.58 μg/mL; WSS: 10.69 μg/mL). No statistically significant correlations were observed between lysozyme, lactoferrin, and sIgA concentrations and the time after alloHSCT. In the group of patients after alloHSCT a negative correlation was found between the resting salivary flow rate and the concentration of lactoferrin and sIgA. The stimulated salivary flow rate correlated negatively with lactoferrin and sIgA concentrations. Additionally, the number of S. mutans colonies correlated positively with the concentration of lysozyme and sIgA. (4) The concentrations of non-specific and specific immunological factors in the saliva of patients after alloHSCT may differ when compared to healthy adults; however, the abovementioned differences did not change with the time after transplantation.

Lactobacilli have played an important role in the gut health of pets. The aim of this research was to study the effects of isolated Lactobacilli (named L11) on the immune, nutrient metabolism, and gut health of cats. Twelve healthy adult cats were randomly assigned into two groups, the control group (CONTROL, n = 6, without any probiotics product) and the treatment group (probiotics, n = 6, L11 109 CFU/kg feed), while using the same dry diet. On day 28, blood and fecal samples were collected, and the blood biochemical indices, fecal microbiota, short-chain fatty acids (SCFAs), immunological parameters, and odorous substances were separately tested. The triglyceride of the blood was decreased after using L11 (p < 0.05), which could probably alleviate the occurrence of cat obesity to some extent. The sIgA of the feces was increased by 30.1% (p < 0.05), which could enhance the cat’s immunity. The abundance of Bifidobacteria was increased after using L11 (p < 0.05), and the indole and 3-methylindole of the feces were both reduced compared with the control group; 3-methylindole was especially reduced by 67.3% (p < 0.05), which showed that L11 could also improve the intestinal state of cats. Therefore, this research shows that L11 could be a good choice to improve the gut health and immune functions of cats, and it is probably related to the lipid mechanism of cats.

Mucosal vaccines protect against respiratory virus infection by stimulating the production of IgA antibodies that protect against virus invasion of the mucosal epithelium. In this study, a novel protein subunit mucosal vaccine was constructed for protection against infection by the beta coronavirus SARS-CoV-2. The vaccine was assembled by linking a gene encoding the SARS-CoV-2 virus S1 angiotensin converting enzyme receptor binding domain (ACE-2-RBD) downstream from a DNA fragment encoding the cholera toxin B subunit (CTB), a mucosal adjuvant known to stimulate vaccine immunogenicity. A 42 kDa vaccine fusion protein was identified in homogenates of transformed E. coli BL-21 cells by acrylamide gel electrophoresis and by immunoblotting against anti-CTB and anti-ACE-2-RBD primary antibodies. The chimeric CTB-SARS-CoV-2-ACE-2-RBD vaccine fusion protein was partially purified from clarified bacterial homogenates by nickel affinity column chromatography. Further vaccine purification was accomplished by polyacrylamide gel electrophoresis and electro-elution of the 42 kDa chimeric vaccine protein. Vaccine protection against SARS-CoV-2 infection was assessed by oral, nasal, and parenteral immunization of BALB/c mice with the CTB-SARS-CoV-2-ACE-2-RBD protein. Vaccine-induced SARS-CoV-2 specific antibodies were quantified in immunized mouse serum by ELISA analysis. Serum from immunized mice contained IgG and IgA antibodies that neutralized SARS-CoV-2 infection in Vero E6 cell cultures. In contrast to unimmunized mice, cytological examination of cell necrosis in lung tissues excised from immunized mice revealed no detectable cellular abnormalities. Mouse behavior following vaccine immunization remained normal throughout the duration of the experiments. Together, our data show that a CTB-adjuvant-stimulated CTB-SARS-CoV-2-ACE-2-RBD chimeric mucosal vaccine protein synthesized in bacteria can produce durable and persistent IgA antibodies in mice that neutralize the SARS-CoV-2 subvariant Omicron BA.1.1.

The level of secretory immunoglobulin A (SIgA) in saliva is associated with the risk of upper respiratory infection and has been identified as a condition indicator for athletes and an indicator of mucosal immune function in the elderly. In addition, it has been suggested that non-specific polyreactive SIgA is present in human saliva and colostrum. The purpose of this study was to establish a new detection method of polyreactive salivary SIgA. Using saliva samples from eight healthy individuals, indirect ELISA was used to detect anti-LPS antibodies (LPS ELISA), and competitive ELISA was used to detect LPS antibodies after competition with DNA (LPS-DNA ELISA). The difference in SIgA concentration between LPS ELISA and LPS-DNA ELISA is thought to be the concentration of the polyreactive SIgA, which responds to both DNA and LPS. First, we determined the concentration for coating LPS and DNA as 10 μg/ml, and the saliva sample dilution was determined as 1/2. The concentration of anti-LPS antibody contained in the saliva sample, which is strongly reactive to LPS, was defined as the standard. Compared to the SIgA concentration determined by LPS ELISA, SIgA concentration of LPS-DNA ELISA did not decrease in two samples, but was reduced in 6 samples. The decrease in SIgA concentration is thought to be the concentration of polyreactive SIgA that reacts with both DNA and LPS. Notably, we found sample-to-sample differences in the concentration of polyreactive SIgA.

The leading role associated with an anti-infective action of breast milk belongs to secretory IgA (SIgA). Therefore, the determination of the level of SIgA in colostrum and milk of mothers with different lactation levels and mothers at risk at different levels and duration of lactation has a practical interest. Aim. The research aims at studying the dynamics of SIgA content in breast milk, taking into account risk factors and features of lactation. Material and Methods. The content of SIgA in colostrum and breast milk of 372 mothers with full lactation and 208 with hypogalactia, of which 72 with early and 146 with late hypogalactia at different times of lactation (1-8 days and 1-3 months) was determined. The SIgA content was also studied in mothers; 65 with preeclampsia, including 12 with early hypogalactia, 24 with late hypogalactia, 23 with full lactation, and 44 with anemia of pregnancy, including 12 with early hypogalactia, 19 with late hypogalactia and 13 with full lactation. The determination of SIgA content in colostrum and milk was performed using the method of simple radial immunodiffusion in a gel by G. Mancini et al. Results and Discussion. The SIgA concentration in colostrum and breast milk decreased during the secretion process. In early hypogalactia, the content of SIgA did not differ significantly from the level of SIgA in colostrum and breast milk with full lactation in the early neonatal period and at 1-3 months of secretion. In the late hypogalactia, SIgA content did not differ significantly from its level in the control group. Due to the lower amount of milk received by the mother's child with hypogalactia, the supply of children with SIgA is insufficient, and the deficit is higher the sooner the hypogalactia develops. Similar changes in the dynamics of SIgA content have been found in mothers with preeclampsia and at different levels of lactation. The exception was the content of SIgA in colostrum and milk of mothers with anemia of pregnancy and early hypogalactia, which in the first five days of lactation was lower than in mothers with full lactation. Conclusion. The SIgA concentration in colostrum and breast milk decreases during the secretion process. The level of lactation does not affect the dynamics of SIgA content, except for the SIgA content in colostrum and breast milk of mothers with anemia of pregnancy and hypogalactia in the early stages of secretion. Despite the absence of a significant difference in SIgA levels in mothers with different levels of lactation due to less colostrum and milk received by children with early and late hypogalactia, the supply of SIgA is insufficient, and the cumulative deficit is higher the faster the hypogalactia develops.

Inflammatory lung diseases represent a persistent burden for patients and the global healthcare system. The combination of high morbidity, (partially) high mortality and limited innovations in the last decades, have resulted in a great demand for new therapeutics. Are therapeutic IgA antibodies possibly a new hope in the treatment of inflammatory lung diseases? Current research increasingly unravels the elementary functions of IgA as protector against infections and as modulator of overwhelming inflammation. With a focus on IgA, this review describes the pathological alterations in mucosal immunity and how they contribute to chronic inflammation in the most common inflammatory lung diseases. The current knowledge of IgA functions in the circulation, and particularly in the respiratory mucosa, are summarized. The interplay between neutrophils and IgA seems to be key in control of inflammation. In addition, the hurdles and benefits of therapeutic IgA antibodies, as well as the currently known clinically used IgA preparations are described. The data highlighted here, together with upcoming research strategies aiming at circumventing the current pitfalls in IgA research may pave the way for this promising antibody class in the application of inflammatory lung diseases.

Recent advances in next-generation sequencing (NGS) technologies have opened the door to a wellspring of information regarding the composition of the gut microbiota. Leveraging NGS technology, early metagenomic studies revealed that several diseases, such as Alzheimer's disease, Parkinson's disease, autism, and myalgic encephalomyelitis, are characterized by alterations in the diversity of gut-associated microbes. More recently, interest has shifted toward understanding how these microbes impact their host, with a special emphasis on their interactions with the brain. Such interactions typically occur either systemically, through the production of small molecules in the gut that are released into circulation, or through signaling via the vagus nerves which directly connect the enteric nervous system to the central nervous system. Collectively, this system of communication is now commonly referred to as the gut-microbiota-brain axis. While equally important, little attention has focused on the causes of the alterations in the composition of gut microbiota. Although several factors can contribute, mucosal immunity plays a significant role in shaping the microbiota in both healthy individuals and in association with several diseases. The purpose of this review is to provide a brief overview of the components of mucosal immunity that impact the gut microbiota and then discuss how altered immunological conditions may shape the gut microbiota and consequently affect neuroimmune diseases, using a select group of common neuroimmune diseases as examples. [ABSTRACT FROM AUTHOR]

The protective effects of molecular crosslinked ready-to-eat sea cucumber (RSC) against immunosuppression induced by cyclophosphamide in mice were investigated. After gavage of molecular crosslinked RSC, the SIgA levels of intestinal mucosa in mice were significantly increased by 31.6% (P < 0.01), and the terminal differentiation of IgA+ B cell was promoted with the significant up-regulation of IL-6 and IL-10 levels. Moreover, the secretion mechanism of plasma cell was mainly promoted through XBP-1s pathway mediated by IRE1 (P < 0.01), rather than ATF-4 and ATF-6 pathway (P > 0.05). In addition, the diversity of intestinal flora was increased, and the imbalance of intestinal flora was improved. The Lachnospiraceae _NK4A136_group dominated in crosslinked group could promote the repair of intestinal mucosa. Therefore, molecular crosslinked RSC can alleviate the intestinal mucosal damage via promoting SIgA secretion and regulating gut microbiota of mice. [ABSTRACT FROM AUTHOR]

Lay summaryAdaptive immune proteins in mothers' milk are more variable than innate immune proteins across populations and subsistence strategies. These results suggest that the immune defenses in milk are shaped by a mother's environment throughout her life.Background and objectivesMother's milk contains immune proteins that play critical roles in protecting the infant from infection and priming the infant's developing immune system during early life. The composition of these molecules in milk, particularly the acquired immune proteins, is thought to reflect a mother's immunological exposures throughout her life. In this study, we examine the composition of innate and acquired immune proteins in milk across seven populations with diverse disease and cultural ecologies.MethodologyMilk samples (n = 164) were collected in Argentina, Bolivia, Nepal, Namibia, Philippines, Poland and the USA. Populations were classified as having one of four subsistence patterns: urban-industrialism, rural-shop, horticulturalist-forager or agro-pastoralism. Milk innate (lactalbumin, lactoferrin and lysozyme) and acquired (Secretory IgA, IgG and IgM) protein concentrations were determined using triple-quadrupole mass spectrometry.ResultsBoth innate and acquired immune protein composition in milk varied among populations, though the acquired immune protein composition of milk differed more among populations. Populations living in closer geographic proximity or having similar subsistence strategies (e.g. agro-pastoralists from Nepal and Namibia) had more similar milk immune protein compositions. Agro-pastoralists had different milk innate immune protein composition from horticulturalist-foragers and urban-industrialists. Acquired immune protein composition differed among all subsistence strategies except horticulturist-foragers and rural-shop.Conclusions and implicationsOur results reveal fundamental variation in milk composition that has not been previously explored in human milk research. Further study is needed to understand what specific aspects of the local environment influence milk composition and the effects this variation may have on infant health outcomes.

Fawzia Hassan Abo Ali,1 Nehal Elfawy Mahmoud,1 Amr Yakout Mohamed El-Sayed,1 Mariam Fathy Abdelmaksoud,2 Alaa K Shata,3 Shaimaa Hani Fouad1 1Department of Internal Medicine/Allergy and Clinical Immunology, Ain-Shams University, Cairo, Egypt; 2Department of Clinical Pathology, Ain-Shams University, Cairo, Egypt; 3Department of Pulmonology, Ain Shams University, Cairo, EgyptCorrespondence: Shaimaa Hani FouadDepartment of Internal Medicine/ Allergy and Clinical Immunology, Ain Shams University, Abbasia, Cairo, 11566, EgyptTel/Fax +202 24346888; Tel +2 01116110004Email shaimaahani@med.asu.edu.egBackground: Selective immunoglobulin A (IgA) deficiency is characterized by a high incidence of both recurrent infections and atopic diseases. Asthma is one of the most common lung diseases affecting around 300 million people worldwide and is associated with risk of serious pneumococcal disease and microbial infections. Multiple studies have attributed this to impaired innate and adaptive immunity in asthmatics. An additional probable hypothesis is the existence of an underlying primary immunodeficiency (PID), such as selective IgA deficiency (sIgAD).Aim: To assess the prevalence of selective IgA deficiency and its correlation to recurrent infections in asthmatic patients.Methods: A case–control study was conducted on 80 subjects who were divided into 3 groups: 20 Asthmatic patients with recurrent chest infections (Group A), 20 asthmatic patients without recurrent chest infections (Group B) and 40 healthy controls (Group C).Results: On comparing the 3 studied groups, there was a statistically significant difference between the three groups (p = ˂0.001) concerning serum IgA. The mean serum IgA was statistically significantly lower in Group A&B than in Group C. Furthermore, it was significantly lower in Group A than in Group B and C (p1,2 < 0.002 and < 0.001&ast;, respectively). The percentage of selective IgA deficiency or partial IgA deficiency in asthmatic patients was 56% (26 patients). Group A showed a statistically significant higher percentage of selective/partial IgA deficiency.Keywords: sIgA, sIgE, sIgM, sIgG, asthma, recurrent infections, immune deficiency

Traditional Chinese medicine (TCM) formulas can be adjusted on the basis of TCM basic theory to achieve the best curative effect, especially for diseases with complex pathogenesis, such as post-weaning diarrhea (PWD). Shugan Jianwei Sijunzi decoction (SJ-SJZD) can be recognized as modified Sijunzi Decoction (SJZD) supplemented with Astragalus mongholicus Bunge, Bupleurum chinense DC, Citrus × aurantium L., and Crataegus pinnatifida Bunge (fruit) in a fixed dosage ratio. The inactive ingredients were subsequently added to make granule, which was Shugan Jianwei Sijunzi granule (SJ-SJZG). Previous studies have confirmed the antagonism of SJ-SJZG to PWD. However, the mechanism of SJ-SJZG protective effects on small intestine in weaned Rex rabbits remained unclear. Animals were randomly divided into negative control (NC), low dose (LD), medium dose (MD), high dose (HD), and positive control (PC). SJ-SJZG significantly increased the intestinal length and the jejunum villi length. The SIgA level was statistically increased in duodenum and jejunum with the ELISA. Immunohistochemical detection showed that SIgA protein expression was also increased significantly in jejunum. Meanwhile, the relative expression of Zo1 in duodenum and jejunum of SJ-SJZG group increased significantly. SJ-SJZG significantly increased the relative expression of occludin in duodenum and jejunum as well. Moreover, real-time PCR results showed a significant increase in GLUT2 and SGLT1 relative expression in ileum. SJ-SJZG could also obviously enhance the expression of GLUT2 in jejunum and the expression of SGLT1 in duodenum. In conclusion, SJ-SJZG had been proven to be effective in promoting the development of small intestine and improving the immunity of small intestine. Moreover, SJ-SJZG could ensure the integrity of mucosal barrier and increase the ability of intestine to absorb glucose in small intestine.

Although the use of the probiotic bacterium Lactobacillus for the treatment and prevention of diseases caused by various pathogenic bacteria has received increasing attention in recent years, its mechanism remains incompletely understood. Levilactobacillus brevis 23017 is a select probiotic strain that can regulate the immunity of host animals and resist pathogen infections. In this study, we analyzed the effect of L. brevis 23017 on Yersinia enterocolitica intestinal infection in a BALB/c mouse model and discussed its underlying mechanism. We found that in the mouse model, L. brevis 23017 prevented the damage of villi in the small intestine and decelerated weight loss after Y. enterocolitica infection. Moreover, we focused on the mechanism of the protective effect of L. brevis 23017 from the perspective of the damage and repair of the intestinal mucosal barrier. We observed that L. brevis 23017 maintained a normal mucosal barrier by altering the expression of tight junction proteins. Notably, our results indicated that L. brevis 23017 effectively promoted the secretion of the intestine-specific secretory immunoglobulin A (SIgA) by B cells via regulating cytokines and oxidative damage levels. This mechanism may be the reason for its protective role in Y. enterocolitica infection. In addition, our results demonstrated that the mechanism of L. brevis 23017 was related to antibacterial colonization and inflammation regulation and closely related to antioxidative stress and SIgA promotion. The protective effect of L. brevis 23017 on mice was related to the signaling pathway protein p38 MAPK and the phosphorylation levels of NF-κB. Our study provided novel insight into the mechanism of Lactobacillus against pathogenic bacterial infections. Such insight is of great importance for the prevention, diagnosis, and treatment of related diseases. [ABSTRACT FROM AUTHOR]

Background: Mucosal immunoglobulin comprises mainly secretory immunoglobulin A (SIgA) which mainly participates in the intestinal mucosal pathogenspecific immune response. Immunoglobulin G (IgG) is another common immunoglobulin. Bactrian camels’ gastrointestinal mucosal tissue has a special mucosal immune system. However, the distribution characteristics of these two antibody-secreting cells (ASCs) in Bactrian camel’s large intestine mucosal immunity system remain largely unknown. This study was aimed to describe the distribution characteristics and density of SIgA and IgG ASCs in the mucosal immunity tissues of Bactrian camel large intestine. Materials and methods: Tissue samples were collected from different parts of the large intestines of 10 healthy adult Chinese Alashan Bactrian camels. Immunohistochemistry technology was used to determine the distribution of SIgA and IgG ASCs in the large intestine samples and the image-Pro Plus 6.0 was employed to calculate their densities. Results: SIgA and IgG ASCs were distributed in lamina propria of the large intestine mucosa with some ASCs aggregating around the intestinal glands. The SIgA density increased from ileocecal orifice to the caecum and decreased from the colon to the rectum. The largest number of SIgA ASCs was observed in the caecum, followed by anterior colonic segments, ileocecal orifice, posterior colonic segments, and rectum, and the number of SIgA ASCs in the caecum was significantly larger than that in other four positions (p < 0.05). Similarly, the number of IgG ASCs was also the largest in the caecum, which was significantly higher than that in ileocecal orifice, anterior, posterior colonic segments, and rectum (p < 0.05). Conclusions: Our findings suggest that SIgA and IgG ASCs are mainly distributed in intestinal mucosal immunity effector sites. These distribution characteristics provide evidence to support that SIgA and IgG supply effective protection and maintain homeostasis in the large intestinal mucosa. [ABSTRACT FROM AUTHOR]

Antibiotic resistance genes are usually tightly controlled by transcription factors and RNA regulatory elements including sRNAs, riboswitches, and attenuators, and their expression is activated to respond to antibiotic exposure. In previous work, we revealed that the rppA gene is regulated by attenuator LRR and two mistranslation products in Bacillus thuringiensis BMB171. However, its function and promoter regulation is still not precise. In this study, we demonstrated that the encoding product of the rppA gene acts as an ARE1 ABC-F protein and confers resistance to antibiotics virginiamycin M1 and lincomycin when overexpressed. Besides the reported attenuator LRR, the expression of the rppA gene is controlled by the sigma factor SigA and a global transcription factor CcpA. Consequently, its promoter activity is mainly maintained at the stationary phase of cell growth and inhibited in the presence of glucose. Our study revealed the function and regulation of the rppA gene in detail. Key points: • The RppA protein acts as an ARE1 ABC-F protein • The rppA gene confers resistance to antibiotics virginiamycin M1 and lincomycin when overexpressed • The expression of the rppA gene is regulated by the sigma factor SigA and the pleiotropic regulator CcpA [ABSTRACT FROM AUTHOR]

Human secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse‐transcytosis, the apical‐to‐basal transport of IgA2 immune complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microbiota requires broad affinity IgA and glycan–glycan interaction. Here, we asked whether IgA1 and IgA2‐microbiota interactions might be involved in dysbiosis induction during inflammatory bowel diseases. Using stool HPLC‐purified IgA, we show that reverse‐transcytosis is abrogated in ulcerative colitis (UC) while it is extended to IgA1 in Crohn's disease (CD). 16S RNA sequencing of IgA‐bound microbiota in CD and UC showed distinct IgA1‐ and IgA2‐associated microbiota; the IgA1+ fraction of CD microbiota was notably enriched in beneficial commensals. These features were associated with increased IgA anti‐glycan reactivity in CD and an opposite loss of reactivity in UC. Our results highlight previously unknown pathogenic properties of IgA in IBD that could support dysbiosis. Synopsis: IBD (both CD and UC) is characterized by dysbiosis and altered immune pathways that lead to and sustain prolonged inflammation in the gut. As IgA are the main drivers of commensal selection in the healthy gut, this study aimed at assessing subclass‐related structure and functions of IgA in both CD and UC. Evidence of a chain of subclass‐dependent functional disparities between CD and UC IgAs affecting antibody glycosylation, transport across epithelia, and affinity, which may interfere in optimal commensal selection to promote dysbiosisWhile only IgA2 could undergo RT in non‐IBD, IgA1 in CD had the ability to do so and neither IgA1 nor IgA2 were able to in UC.Despite predominant dual IgA1 and IgA2 binding on stool microbiota, CD associates with enriched commensal binding in the IgA1+ fraction, and UC with a marked reduction in IgA overall reactivity [ABSTRACT FROM AUTHOR]

Background: JYNNEOS is a nonreplicating modified vaccinia Ankara vaccine currently licensed to prevent monkeypox infection, and its milk immunogenicity remains unstudied. Objective: Investigate the human milk immunogenicity of the JYNNEOS vaccine in one individual and examine the milk for evidence of vaccine components. Methods: Immunogenicity of milk and plasma samples were tested by Luminex assays against Vaccinia antigens, and vaccine components were tested using PCR and sandwich ELISA. Results: Plasma antibody (Ab) response increased up to 3.7-fold in immunoglobulin G (IgG) titer and 1.4-fold in IgA compared with baseline, confirming vaccine immunogenicity in this participant 2 weeks post dose 2. Specific plasma IgG remained 1.2- to 1.7-fold above baseline 12 weeks post dose 2, while IgA returned to baseline levels. Notably, the milk response exhibited unique kinetics, particularly for IgA. Milk IgA against all three antigens increased 0.9- to 2.2-fold 2 weeks post dose 2, reaching a peak titer increase of 1.1- to 2.7-fold at 12 weeks post dose 2. Secretory (s) Ab levels increased to 1.1- to 2-fold at 2 weeks post dose 2 and reached a peak of 2- to 3.2-fold increase at the 12-week time point. Importantly, IgA and sAb responses in milk exhibited correlation, suggesting most milk IgA was sIgA. Notably, no vaccine components (VACV protein or DNA) were detected in the milk samples. Conclusion: These data suggest that the milk Ab response to this intradermal (ID) VACV-based vaccine is distinct from that observed systemically, indicating a unique mucosal immune response and highlighting its potential to elicit protective long-lasting sIgA. This case report provides strong evidence for inclusion of this vaccine platform in future studies of maternal vaccines aimed to elicit a protective milk Ab response.

Abstract Human secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse‐transcytosis, the apical‐to‐basal transport of IgA2 immune complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microbiota requires broad affinity IgA and glycan–glycan interaction. Here, we asked whether IgA1 and IgA2‐microbiota interactions might be involved in dysbiosis induction during inflammatory bowel diseases. Using stool HPLC‐purified IgA, we show that reverse‐transcytosis is abrogated in ulcerative colitis (UC) while it is extended to IgA1 in Crohn's disease (CD). 16S RNA sequencing of IgA‐bound microbiota in CD and UC showed distinct IgA1‐ and IgA2‐associated microbiota; the IgA1+ fraction of CD microbiota was notably enriched in beneficial commensals. These features were associated with increased IgA anti‐glycan reactivity in CD and an opposite loss of reactivity in UC. Our results highlight previously unknown pathogenic properties of IgA in IBD that could support dysbiosis.

Donor human milk (DHM) is the second-best nutrition for preterm infants when their own mother’s milk is unavailable. The nutrient content of human milk is influenced by various factors, including gestational and postpartum age, but there are no data regarding DHM composition in Japan. The aim of this study was to determine the protein and immune component content of DHM in Japan and to elucidate the effects of gestational and postpartum age on nutrient composition. From September 2021 to May 2022, 134 DHM samples were collected from 92 mothers of preterm and term infants. Protein concentrations in preterm DHM (n = 41) and term DHM (n = 93) were analyzed using a Miris Human Milk Analyzer. The concentrations of secretory immunoglobulin A (sIgA) and lactoferrin, major immune components, were measured using enzyme-linked immunosorbent assays. Preterm DHM exhibited higher protein content than term DHM (1.2 g/dL and 1.0 g/dL, respectively, p < 0.001), whereas sIgA content was higher in term DHM than in preterm DHM (110 μg/mL and 68.4 μg/mL, respectively, p < 0.001). Gestational age was negatively correlated with protein levels and positively correlated with sIgA and lactoferrin levels. Furthermore, a negative correlation was found between postpartum week and protein, sIgA, and lactoferrin concentrations. Our data suggest that gestational and postpartum age affects protein, sIgA, and lactoferrin concentrations in DHM. These results indicate the importance of nutritional analysis for the appropriate use of DHM in preterm infants.

The intramuscular vaccine is the principal strategy to protect pigs from porcine reproductive and respiratory syndrome virus (PRRSV), However, it is still difficult to control PRRSV effectively. This study infected piglets with PRRSV through intramuscular and intranasal inoculation. Subsequently, viral loads, anti-PRRSV antibody levels, and neutralizing antibodies (NAs) titers in both serum and saliva were monitored for 43 days. Meanwhile, tissues were obtained through necropsy at 43 days post-inoculation (dpi) to detect viral loads. The results indicated that viremia lasted from 3 to 31 dpi in both the inoculation groups, but the viruses survived in the lungs and lymph nodes after viremia clearance. The antibody response was detected from 11 dpi, but the response of NAs was delayed until 3–4 weeks. Furthermore, intranasal inoculation induced lower viral load levels than injection inoculation. In addition, positive SIgA and NAs levels were produced early, with higher levels through intranasal inoculation. Therefore, our data indicated that a more robust antibody response and lower virus loads could be induced by intranasal inoculation, and mucosal inoculation could be a suitable pathway for PRRSV vaccines. [ABSTRACT FROM AUTHOR]