Mucosal Immunoglobulin Research Articles

Oral administration enhances directly mucosal immune system in intestine of olive flounder (Paralichthys olivaceus)

Aquaculture is notably vulnerable to diseases, with Edwardsiella tarda causing significant mortality across various commercially important fish species in both freshwater and marine environments. In the aquaculture industry, sustainable disease control hinges on the effective development of vaccines. Oral vaccines present an appealing approach to immunization in fish due to their ease of antigen administration, reduced stress compared to non-oral delivery methods, and their potential applicability to both small and large finfish species. In mammals, the exposure of mucosal surfaces to antigens results in the secretion of antigen-specific IgA at these locations. Mammals have a common mucosal immune system, in which stimulation of one epithelium can also give rise to specific IgA or IgM responses in other mucosal organs. Mucosal immunoglobulins are particularly important in developing vaccines that provide mucosal immunity. However, it remains unclear whether fish share a common mucosal system. Moreover, neither Peyer's patches nor intestinal lymph nodes were identified. Nevertheless, oral vaccination remains an attractive method for inducing immunity. We investigated whether the activation of the mucosal immune response was induced by direct injection of the antigen. After oral antigen administration, antigen-specific antibody titers increased in the experimental group (E. tarda FKC vaccine). In the challenge experiment, the cumulative survival rate was 72% (E. tarda). This suggests that oral administration of antigens can activate intestinal mucosal immunity in flounders. Additionally, these results help understand the intestinal mucosal immune system of teleost fish. In the future, research on the signaling mechanisms of these genes is expected to provide helpful information for developing vaccine adjuvants.

Recombinant OC43 SARS-CoV-2 spike replacement virus: An improved BSL-2 proxy virus for SARS-CoV-2 neutralization assays

We generated a replication-competent OC43 human seasonal coronavirus (CoV) expressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike in place of the native spike (rOC43-CoV2 S). This virus is highly attenuated relative to OC43 and SARS-CoV-2 in cultured cells and animals and is classified as a biosafety level 2 (BSL-2) agent by the NIH biosafety committee. Neutralization of rOC43-CoV2 S and SARS-CoV-2 by S-specific monoclonal antibodies and human sera is highly correlated, unlike recombinant vesicular stomatitis virus-CoV2 S. Single-dose immunization with rOC43-CoV2 S generates high levels of neutralizing antibodies against SARS-CoV-2 and fully protects human ACE2 transgenic mice from SARS-CoV-2 lethal challenge, despite nondetectable replication in respiratory and nonrespiratory organs. rOC43-CoV2 S induces S-specific serum and airway mucosal immunoglobulin A and IgG responses in rhesus macaques. rOC43-CoV2 S has enormous value as a BSL-2 agent to measure S-specific antibodies in the context of a bona fide CoV and is a candidate live attenuated SARS-CoV-2 mucosal vaccine that preferentially replicates in the upper airway.

Equine herpesvirus type 1 (EHV-1) replication at the upper respiratory entry site is inhibited by neutralizing EHV-1-specific IgG1 and IgG4/7 mucosal antibodies.

Equine herpesvirus type 1 (EHV-1) is a contagious respiratory pathogen that infects the mucosa of the upper respiratory tract (URT). Mucosal immune responses at the URT provide the first line of defense against EHV-1 and are crucial for orchestrating immunity. To define host-pathogen interactions, we characterized B-cell responses, antibody isotype functions, and EHV-1 replication of susceptible (non-immune) and clinically protected (immune) horses after experimental EHV-1 infection. Nasal secretion and nasal wash samples were collected and used for the isolation of DNA, RNA, and mucosal antibodies. Shedding of infectious virus, EHV-1 copy numbers, viral RNA expression, and host B-cell activation in the URT were compared based on host immune status. Mucosal EHV-1-specific antibody responses were associated with EHV-1 shedding and viral RNA transcription. Finally, mucosal immunoglobulin G (IgG) and IgA isotypes were purified and tested for neutralizing capabilities. IgG1 and IgG4/7 neutralized EHV-1, while IgG3/5, IgG6, and IgA did not. Immune horses secreted high amounts of mucosal EHV-1-specific IgG4/7 antibodies and quickly upregulated B-cell pathway genes, while EHV-1 was undetected by virus isolation and PCR. RNA transcription analysis reinforced incomplete viral replication in immune horses. In contrast, complete viral replication with high viral copy numbers and shedding of infectious viruses was characteristic for non-immune horses, together with low or absent EHV-1-specific neutralizing antibodies during viral replication. These data confirm that pre-existing mucosal IgG1 and IgG4/7 and rapid B-cell activation upon EHV-1 infection are essential for virus neutralization, regulation of viral replication, and mucosal immunity against EHV-1.IMPORTANCEEquine herpesvirus type 1 (EHV-1) causes respiratory disease, abortion storms, and neurologic outbreaks known as equine herpes myeloencephalopathy (EHM). EHV-1 is transmitted with respiratory secretions by nose-to-nose contact or via fomites. The virus initially infects the epithelium of the upper respiratory tract (URT). Host-pathogen interactions and mucosal immunity at the viral entry site provide the first line of defense against the EHV-1. Robust mucosal immunity can be essential in protecting against EHV-1 and to reduce EHM outbreaks. It has previously been shown that immune horses do not establish cell-associated viremia, the prerequisite for EHM. Here, we demonstrate how mucosal antibodies can prevent the replication of EHV-1 at the epithelium of the URT and, thereby, the progression of the virus to the peripheral blood. The findings improve the mechanistic understanding of mucosal immunity against EHV-1 and can support the development of enhanced diagnostic tools, vaccines against EHM, and the management of EHV-1 outbreaks.

Fulvic acid modulates mucosal immunity in fish skin: Sustainable aquaculture solution or environmental risk factor?

This is the first study determining the effects of bath exposure to fulvic acid, a humic substance, on the skin mucosal immunity of rainbow trout (Oncorhynchus mykiss). Humic substances have recently been gaining attention for their increasing concentrations in aquatic ecosystems and their use as supplements in sustainable aquaculture. This study demonstrated that water exposure to fulvic acid at concentrations of 5 mg C/L and 50 mg C/L increased lysozyme and alkaline phosphatase activities in the mucus by approximately 2-fold and 2.5 to 3.2-fold, respectively. Furthermore, exposure to 50 mg C/L resulted in a 77.0% increase in mucosal immunoglobulin concentrations compared to the other groups. Importantly, all mucus samples demonstrated significant antibacterial activity against Yersinia ruckeri, with control mucus reducing bacterial growth by 44.5% and exposure to fulvic acid increasing this effect to 26.3%. Although these modulations show promise for application in aquaculture, alterations of the beneficial microbiota from long-term exposure in natural waters can be expected. Monitoring the rising concentrations of humic substances in natural water bodies is therefore urgently needed. Overall, this study represents the first investigation revealing the ability of humic substances to modulate skin mucosal immunity and the capacity to combat microorganisms.

Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents infection of Omicron lineages.

The emergence of Omicron lineages and descendent subvariants continues to present a severe threat to the effectiveness of vaccines and therapeutic antibodies. We have previously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by the mRNA vaccines is associated with a surge in breakthrough infections. Here, we further show that the intramuscular mRNA and/or inactivated vaccines cannot sufficiently boost the mucosal secretory IgA response in uninfected individuals, particularly against the Omicron variant. We thus engineered and characterized recombinant monomeric, dimeric, and secretory IgA1 antibodies derived from four neutralizing IgG monoclonal antibodies (mAbs 01A05, rmAb23, DXP-604, and XG014) targeting the receptor-binding domain of the spike protein. Compared to their parental IgG antibodies, dimeric and secretory IgA1 antibodies showed a higher neutralizing activity against different variants of concern (VOCs), in part due to an increased avidity. Importantly, the dimeric or secretory IgA1 form of the DXP-604 antibody significantly outperformed its parental IgG antibody, and neutralized the Omicron lineages BA.1, BA.2, and BA.4/5 with a 25- to 75-fold increase in potency. In human angiotensin converting enzyme 2 (ACE2) transgenic mice, a single intranasal dose of the dimeric IgA DXP-604 conferred prophylactic and therapeutic protection against Omicron BA.5. Thus, dimeric or secretory IgA delivered by nasal administration may potentially be exploited for the treatment and prevention of Omicron infection, thereby providing an alternative tool for combating immune evasion by the current circulating subvariants and, potentially, future VOCs.

DOES HIGH-INTENSITY RESISTANCE TRAINING AFFECT AN ATHLETE'S IMMUNE FUNCTIONS?

This research aims to comprehensively examine the latest literature on the effects of high-intensity resistance training on the immune system's long-term performance. Many athletes and active individuals believe that moderate physical activity can enhance resistance to minor illnesses like upper respiratory tract infections (URTI), while intense exercise may have the opposite effect. The study involved 90 athletes who regularly train at Ahly Sporting Club and were divided into three groups: Group 1 included 30 athletes at rest, Group 2 comprised 30 athletes after normal training, and Group 3 had 30 athletes after intense training. Athletes who undergo intense training have lower total white blood cell counts than those who train at normal or resting levels. However, their neutrophil numbers slightly increase after heavy training, while lymphocyte and natural killer cell levels decrease. Additionally, those who undergo heavy training have higher PHA-induced proliferation levels but show a decline in serum immunoglobulin levels, mucosal immunoglobulin concentrations, and plasma glutamine levels. To prevent upper respiratory tract infections in athletes, it is essential to avoid over training and provide sufficient rest and recovery during and after training and competition. It is currently uncertain whether moderate exercise training can prevent infectious illness among the general population.

Critical Signaling Transduction Pathways and Intestinal Barrier: Implications for Pathophysiology and Therapeutics.

The intestinal barrier is a sum of the functions and structures consisting of the intestinal mucosal epithelium, mucus, intestinal flora, secretory immunoglobulins, and digestive juices. It is the first-line defense mechanism that resists nonspecific infections with powerful functions that include physical, endocrine, and immune defenses. Health and physiological homeostasis are greatly dependent on the sturdiness of the intestinal barrier shield, whose dysfunction can contribute to the progression of numerous types of intestinal diseases. Disorders of internal homeostasis may also induce barrier impairment and form vicious cycles during the response to diseases. Therefore, the identification of the underlying mechanisms involved in intestinal barrier function and the development of effective drugs targeting its damage have become popular research topics. Evidence has shown that multiple signaling pathways and corresponding critical molecules are extensively involved in the regulation of the barrier pathophysiological state. Ectopic expression or activation of signaling pathways plays an essential role in the process of shield destruction. Although some drugs, such as molecular or signaling inhibitors, are currently used for the treatment of intestinal diseases, their efficacy cannot meet current medical requirements. In this review, we summarize the current achievements in research on the relationships between the intestinal barrier and signaling pathways. The limitations and future perspectives are also discussed to provide new horizons for targeted therapies for restoring intestinal barrier function that have translational potential.

Salivary secretory immunoglobulin A as a potential biomarker of psychosocial stress response during the first stages of life: A systematic review

Mucosal secretory immunoglobulin A (s-IgA) has been recognized as a key component of human first line defense against infection. However, its reactivity to psychosocial stressors is poorly understood. This systematic review aimed to explore whether s-IgA levels changed after psychosocial stress in subjects under the age of 18. Fifteen articles were included. s-IgA basal levels are increased in children older than 9 years old exposed to stress. Furthermore, s-IgA seems to follow a circadian rhythm, which is altered under stress conditions. Finally, the collective evidence suggests that salivary s-IgA rapidly increases under acute stress after puberty. Overall, our review indicates that s-IgA could be considered a potential psychosocial stress biomarker of interest for pediatric and child-juvenile psychiatric population. Further studies are needed to validate the role of s-IgA circadian rhythm and basal levels as psychosocial stress biomarkers and disentangle the role of age and type of stressor.

Effects of tannic acid on the immunity and intestinal health of broiler chickens with necrotic enteritis infection

BackgroundIn broiler chickens, necrotic enteritis (NE) infection can reduce production performance. Tannic acid has shown great potential as a treatment of NE in broilers. However, the appropriate dosage of tannic acid in NE of broilers and the improvement effect on intestinal health are not very clear. In this study, we aimed to investigate the effects of different doses of tannic acid on the production performance, immunity, and intestinal health of broilers by constructing an NE model with C. perfringens infection and determining the appropriate dosage of tannic acid with regard to NE.ResultsChallenged birds showed significant reduction in body weight, villus height, and the ratio of villus height to crypt depth (P < 0.05) and increase in the feed consumption gain ratio, intestinal lesion score, and crypt depth (P < 0.05). The infection significantly reduced the relative Bacteroidota and Ligilactobacillus abundance (P < 0.05) and increased the ratio of Firmicutes/Bacteroidota and cecal content of C. perfringens (P < 0.05). Challenged birds fed diets supplemented with tannic acid showed significantly increased mRNA expression of nutrient transport carriers and intestinal barrier genes and growth performance and reduced serum zonulin and endotoxin levels (P < 0.05). Addition of tannic acid to the diet inhibited the inflammatory response by reducing the number of coccidia oocysts in feces and the content of C. perfringens in the cecum. Specifically, tannic acid reduced the serum levels of C reactive protein, myeloperoxidase, and specific IgY and ileal mucosal secretory immunoglobulin A levels in the ileal mucosa compared with those in the NE-infected birds. NE-infected birds fed diets supplemented with tannic acid also showed significantly increased relative Anaerocolumna, Thermoanaerobacterium, and Thermosinus abundance (P < 0.05); their microbial composition and functional predictions were similar to those of the NC group.ConclusionsTannic acid in the diet alleviated NE by enhancing the intestinal barrier and absorption function. The recommended dietary tannic acid additive level is 500–750 mg/kg. Our study findings would be useful in reducing related economic losses in the broiler industry.

Association of plasma zinc levels with anti-SARS-CoV-2 IgG and IgA seropositivity in the general population: A case–control study

Some micronutrients have key roles in immune defence, including mucosal defence mechanisms and immunoglobulin production. Altered micronutrient status has been linked with COVID-19 infection and disease severity. We assessed the associations of selected circulating micronutrients with anti-SARS-CoV-2 IgG and IgA seropositivity in the Swiss community using early pandemic data. Case-control study comparing the first PCR-confirmed COVID-19 symptomatic cases in the Vaud Canton (May to June 2020, n=199) and controls (random population sample, n=447), seronegative for IgG and IgA. The replication analysis included seropositive (n=134) and seronegative (n=152) close contacts from confirmed COVID-19 cases. Anti-SARS-CoV-2 IgG and IgA levels against the native trimeric spike protein were measured using the Luminex immunoassay. We measured plasma Zn, Se and Cu concentrations by ICP-MS, and 25-hydroxy-vitamin D3 (25(OH)D3) with LC-MS/MS and explored associations using multiple logistic regression. The 932 participants (54.1% women) were aged 48.6±20.2 years (±SD), BMI 25.0±4.7kg/m2 with median C-Reactive Protein 1mg/l. In logistic regressions, log2(Zn) plasma levels were negatively associated with IgG seropositivity (OR [95% CI]: 0.196 [0.0831; 0.465], P<0.001; replication analyses: 0.294 [0.0893; 0.968], P<0.05). Results were similar for IgA. We found no association of Cu, Se, and 25(OH)D3 with anti-SARS-CoV-2 IgG or IgA seropositivity. Low plasma Zn levels were associated with higher anti-SARS-CoV-2 IgG and IgA seropositivity in a Swiss population when the initial viral variant was circulating, and no vaccination available. These results suggest that adequate Zn status may play an important role in protecting the general population against SARS-CoV-2 infection. CORONA IMMUNITAS:: ISRCTN18181860.

Oral Immunization with Escherichia coli Nissle 1917 Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice

As of October 2022, the COVID-19 pandemic continues to pose a major public health conundrum, with increased rates of symptomatic infections in vaccinated individuals. An ideal vaccine candidate for the prevention of outbreaks should be rapidly scalable, easy to administer, and able to elicit a potent mucosal immunity. Towards this aim, we proposed an engineered Escherichia coli (E. coli) Nissle 1917 (EcN) strain with SARS-CoV-2 spike protein (SP)-coding plasmid, which was able to expose SP on its cellular surface by a hybridization with the adhesin involved in diffuse adherence 1 (AIDA1). In this study, we presented the effectiveness of a 16-week intragastrically administered, engineered EcN in producing specific systemic and mucosal immunoglobulins against SARS-CoV-2 SP in mice. We observed a time-dependent increase in anti-SARS-CoV-2 SP IgG antibodies in the sera at week 4, with a titre that more than doubled by week 12 and a stable circulating titre by week 16 (+309% and +325% vs. control; both p < 0.001). A parallel rise in mucosal IgA antibody titre in stools, measured via intestinal and bronchoalveolar lavage fluids of the treated mice, reached a plateau by week 12 and until the end of the immunization protocol (+300, +47, and +150%, at week 16; all p < 0.001 vs. controls). If confirmed in animal models of infection, our data indicated that the engineered EcN may be a potential candidate as an oral vaccine against COVID-19. It is safe, inexpensive, and, most importantly, able to stimulate the production of both systemic and mucosal anti-SARS-CoV-2 spike-protein antibodies.

Versatility of bacterial outer membrane vesicles in regulating intestinal homeostasis

Outer membrane vesicles (OMVs) play vital roles in bacterial communication both intraspecifically and interspecifically. However, extracellular mechanisms of gut microbiota-derived OMVs in the intestine remain poorly understood. Here, we report that OMVs released from Akkermansia muciniphila are able to (i) restore disturbed balance of the gut microbiota by selectively promoting the proliferation of beneficial bacteria through membrane fusion, (ii) elicit mucosal immunoglobulin A response by translocating into Peyer's patches and subsequently activating B cells and dendritic cells, and (iii) maintain the integrity of the intestinal barrier by entering intestinal epithelial cells to stimulate the expressions of tight junctions and mucus. We demonstrate that transplantation of gut microbiota-associated OMVs to the intestine can alleviate colitis and enhance anti-programmed cell death protein 1 therapy against colorectal cancer by regulating intestinal homeostasis. This work discloses the importance of gut microbiota-derived OMVs in intestinal ecology, providing an alternative target for disease intervention and treatment.

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders.

Current approved COVID-19 vaccines, notably mRNA and adenoviral vectored technologies, still fail to fully protect against infection and transmission of various SARS-CoV-2 variants. The mucosal immunity at the upper respiratory tract represents the first line of defense against respiratory viruses such as SARS-CoV-2 and is thus critical to develop vaccine blocking human-to-human transmission. We measured systemic and mucosal Immunoglobulin A (IgA) response in serum and saliva from 133 healthcare workers from Percy teaching military hospital following a mild infection (SARS-CoV-2 Wuhan strain, n=58) or not infected (n=75), and after SARS-CoV-2 vaccination (Vaxzevria®/Astrazeneca and/or Comirnaty®/Pfizer). While serum anti-SARS-CoV-2 Spike IgA response lasted up to 16 months post-infection, IgA response in saliva had mostly fallen to baseline level at 6 months post-infection. Vaccination could reactivate the mucosal response generated by prior infection, but failed to induce a significant mucosal IgA response by itself. Early post-COVID-19 serum anti-Spike-NTD IgA titer correlated with seroneutralization titers. Interestingly, its saliva counterpart positively correlated with persistent smell and taste disorders more than one year after mild COVID-19. As breakthrough infections have been correlated with IgA levels, other vaccine platforms inducing a better mucosal immunity are needed to control COVID-19 infection in the future. Our results encourage further studies to explore the prognosis potential of anti-Spike-NTD IgA in saliva at predicting persistent smell and taste disorders.

Dietary Lactobacillus helveticus and Gum Arabic improves growth indices, digestive enzyme activities, intestinal microbiota, innate immunological parameters, antioxidant capacity, and disease resistance in common carp

The present study aimed at determining the effects of Lactobacillus helveticus (LH), Gum Arabic (GA; natural prebiotic), and their combination as synbiotic on growth performance, digestive enzymes activity, gut microbiota, innate immunity status, antioxidant capacity, and disease resistance against Aeromonas hydrophyla in common carp, Cyprinus carpio for 8 weeks. For this, 735 common carp juveniles (Mean ± standard deviation; 22.51 ± 0.40 g) were fed with 7 different diets including basal diet (C), LH1 (1 × 107 CFU/g), LH2 (1 × 109 CFU/g), GA1 (0.5%), GA2 (1%), LH1+GA1 (1 × 107 CFU/g + 0.5%), and LH2+GA2 (1 × 109 CFU/g + 1%) for 8 weeks. Dietary supplementation with GA and/or LH significantly increased growth performance, WBC, serum total immunoglobulin, superoxide dismutase and catalase activities, skin mucus lysozyme and total immunoglobulin and intestinal lactic acid bacteria. Whereas there were significant improvements in various parameters tested in different treatments, the highest improvement in growth performance, WBC, monocyte/neutrophil percentages, serum lysozyme, alternative complement, glutathione peroxidase and malondialdehyde, skin mucosal alkaline phosphatase, protease, and immunoglobulin, intestinal total bacterial count, protease and amylase activities were observed in the synbiotic treatments, particularly LH1+GA1. After an experimental infection with Aeromonas hydrophila, all experimental treatments exhibited significantly higher survival, compared to the control treatment. The highest survival was related to the synbiotic (particularly LH1+GA1), followed by prebiotic, and probiotic treatments. Overall, synbiotic containing 1 × 107 CFU/g LH + 0.5% GA can improve growth rate and feed efficiency in common carp. Moreover, the synbiotic can improve the antioxidant/innate immune systems and dominate lactic acid bacteria in the fish intestine that may be the reasons of the highest resistance against A. hydrophila infection.

Identification and characterization of immunoglobulin tau (IgT) in Asian Seabass (Lates calcarifer) and mucosal immune response to nervous necrosis virus.

Mucosal immunity plays a critical role in the protection of teleost fish against infection, but mucosal immunoglobulin of important aquaculture species unique to Southeast Asia remained greatly understudied. In this study, the sequence of immunoglobulin T (IgT) from Asian sea bass (ASB) is described for the first time. IgT of ASB possesses the characteristic structure of immunoglobulin with a variable heavy chain and four CH4 domains. The CH2-CH4 domains and full-length IgT were expressed and CH2-CH4 specific antibody was validated against full-length IgT expressed in Sf9 III cells. Subsequent use of the anti-CH2-CH4 antibody in immunofluorescence staining confirmed the presence of IgT-positive cells in the ASB gill and intestine. The constitutive expression of ASB IgT was characterized in different tissues and in response to red-spotted grouper nervous necrosis virus (RGNNV) infection. The highest basal expression of secretory IgT (sIgT) was observed in the mucosal and lymphoid tissues such as the gills, intestine and head kidney. Following NNV infection, IgT expression was upregulated in the head kidney and mucosal tissues. Moreover, a significant increase in localized IgT was found in gills and intestines of infected fish on day 14 post-infection. Interestingly, a significant increase in NNV-specific IgT secretion was only observed in the gills of the infected group. Our results suggest that ASB IgT may play an important role in the adaptive mucosal immune responses against viral infection and could potentially be adapted as a tool for the evaluation of prospective mucosal vaccines and adjuvants for the species.

The diarrheal mechanism of mice with a high-fat diet in a fatigued state is associated with intestinal mucosa microbiota.

Growing evidence has demonstrated that fatigue and a high-fat diet trigger diarrhea, and intestinal microbiota disorder interact with diarrhea. However, the association of intestinal mucosal microbiota with fatigue and high-fat diet trigger diarrhea remains unclear. The specific pathogen-free Kunming male mice were randomly divided into the normal group (MCN), standing group (MSD), lard group (MLD), and standing united lard group (MSLD). Mice in the MSD and MSLD groups stood on the multiple-platform apparatus for four h/d for fourteen consecutive days. From the eighth day, mice in the MLD and MSLD groups were intragastric lard, 0.4mL/each, twice a day for seven days. Subsequently, we analyzed the characteristics and interaction relationship of intestinal mucosal microbiota, interleukin-6 (IL-6), interleukin-17 (IL-17), malondialdehyde (MDA), superoxide dismutase (SOD), and secretory immunoglobulin A (sIgA). Results showed that mice in the MSLD group had an increased number of bowel movements. Compared with the MCN group, the contents of IL-17, and IL-6 were higher (p > 0.05), and the content of sIgA was lower in the MSLD group (p > 0.05). MDA and SOD increased in MLD and MSLD groups. Thermoactinomyces and Staphyloccus were the characteristic bacteria of the MSLD group. And Staphyloccus were positively correlated with IL-6, IL-17, and SOD. In conclusion, the interactions between Thermoactinomyces, Staphyloccus and intestinal inflammation, and immunity might be involved in fatigue and high-fat diet-induced diarrhea.

Dynamics of Anti-influenza Mucosal IgA Over a Season in a Cohort of Individuals Living or Working in a Long-term Care Facility.

Serological surveys are used to ascertain influenza infection and immunity, but evidence for the utility of mucosal immunoglobulin A (IgA) as a correlate of infection or protection is limited. We performed influenza-like illness (ILI) surveillance on 220 individuals living or working in a retirement community in Gainesville, Florida from January to May 2018, and took pre- and postseason nasal samples of 11 individuals with polymerase chain reaction (PCR)-confirmed influenza infection and 60 randomly selected controls. Mucosal IgA against 10 strains of influenza was measured from nasal samples. Overall, 28.2% and 11.3% of individuals experienced a 2-fold and 4-fold rise, respectively, in mucosal IgA to at least 1 influenza strain. Individuals with PCR-confirmed influenza A had significantly lower levels of preseason IgA to influenza A. Influenza-associated respiratory illness was associated with a higher rise in mucosal IgA to influenza strains of the same subtype, and H3N2-associated respiratory illness was associated with a higher rise in mucosal IgA to other influenza A strains. By comparing individuals with and without influenza illness, we demonstrated that mucosal IgA is a correlate of influenza infection. There was evidence for cross-reactivity in mucosal IgA across influenza A subtypes.

Intranasal COVID-19 vaccine: a modern vaccination approach.

Dear Editor, The emergence of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) which was originally reported to WHO in December 2019 resulted in the coronavirus illness and it was subsequently declared a global coronavirus disease 2019 (COVID-19) pandemic in March 2020. Recurring disease outbreaks repeatedly overloaded the public health sector, infecting over 613 million people and killing more than 6.5 million as of September 20221. As new strains emerge and natural immunity wanes, the population, particularly immunocompromised individuals, stand an increased risk of severe sickness and death due to this disease. Various research advances paved the way for developing multiple COVID-19 vaccines which have been approved to treat and prevent COVID-19. Currently, available COVID-19 vaccines including mRNA vaccines, recombinant adenovirus vaccines, and recombinant protein vaccines that have received Emergency Use Authorization (EUA) and have been subsequently used to immunize millions of people are all administered through intramuscular injection2. Intramuscular vaccines have been designed to induce antibody-mediated and cell-mediated immune responses and minimal to no detectable mucosal immunity at the site of infection. Since the nose and upper respiratory tract are the primary routes for inhalation pathogens like SARS-CoV-2 and are more susceptible to infection,3 the vaccine response generated after intramuscular immunization can leave the upper respiratory tract vulnerable to viral replication and dissemination because these vaccines are inefficient in stimulating immunoglobulin A secretion in mucosal cells2. Alternatively, it has been found recently that the intranasal (IN) vaccines for COVID-19 have shown a promising ability to induce sterilizing mucosal immunity against mucosal pathogens apart from inducing an antibody-mediated immune response and a robust cell-mediated immunity2. A single dose of effective SARS-CoV-2 vaccine via IN route boosts mucosal immunoglobulin A and T-cell responses in both upper and lower respiratory tract, providing almost complete prevention against viral infection, multiplication, and reducing virus shedding via nasal mucosa that acts as a first-line barrier to the virus entrance before spreading into the lungs2. This immediate protection at the site of infection by restricting the viral replication and clearance of SARS-CoV-2 infection reflects the potency of IN COVID-19 vaccines in the alleviation of seeding new cases of COVID-19 amidst the pandemic; hence, preventing even mild cases of illness and inhibiting the virus transmission to other people. In addition, these vaccines are minimally invasive, have a needle-free mode of administration, and are usually in the form of a nasal spray2. Owing to the easy transportation and storage, these vaccines are also more convenient to use2. However, an essential consideration for IN COVID-19 vaccine is its safety. An extremely rare risk of reversion of live attenuated virus into replicating state, regaining its ability to cause disease in the individual has been observed4. With that, the effectiveness of the vaccine is determined by the immunization type chosen and the addition of essential adjuvants. Phase I, II, and III clinical trials were performed to assess the efficacy of IN COVID-19 immunization by two companies; CanSino Biologics, a Chinese pharmaceutical company, and Bharat Biotech International, a biotechnology company headquartered in India, which received approval in their respective countries for its use after gaining successful results5. These companies have created ‘viral vector’ vaccines that use a harmless adenovirus to deliver the genetic material of the SARS-CoV-2 into host cells. Given the severity of the situation where the healthcare systems are challenged globally due to increased COVID-19-related hospitalizations, it is critical to continue developing effective and reliable COVID-19 vaccines in present times. In the context of respiratory pathogens like SARS-CoV-2, IN vaccines’ pros conceivably outweigh their cons, along with offering both localized protection at the site of infection and activating systemic responses as compared with intramuscular vaccines eliciting only systemic responses. Large-scale clinical studies and trials should be conducted to gather further evidence to prove its effectiveness so that the availability of IN COVID-19 vaccines may be made feasible. This vaccine might also serve as an alternative to limited and inadequate vaccine supplies as well as a booster to intramuscular vaccines. Immunization with IN COVID-19 vaccines will hopefully help deal with the persistent COVID-19 pandemic and potential viral contagious diseases that might arise in the future. Ethics approval Not applicable. Sources of funding None. Authors’ contribution All authors contributed equally. Conflicts of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration Unique Identifying number (UIN) None. Guarantor Govinda Khatri.

Effects of Bougainvillea glabra leaf on growth, skin mucosal immune responses, and disease resistance in common carp Cyprinus carpio

This study evaluated the effects of Bougainvillea glabra (BG) leaf as a feed supplement on growth, skin mucosal immune parameters, serum oxidative stress, expression of immune-related genes, and susceptibility to pathogen infection in carp Cyprinus carpio. Diets containing four different BG concentrations (g kg−1), i.e., 0 g (basal diet), 20 g (BG20), 30 g (BG30), 40 g (BG40), and 50 g (BG50), were fed to the carp (average weight: 14.03 ± 0.81 g) for 8 weeks. Skin mucosal immunological and serum antioxidant parameters were examined 8 weeks post-feeding. Growth performance was significantly higher in BG40. Among the examined skin mucosal immune parameters, lysozyme (33.79 ± 0.98 U mL−1), protein (6.88 ± 0.37 mg mL−1), immunoglobulin (IgM; 5.34 ± 0.37 unit-mg mL−1), and protease activity (3.18 ± 0.36%) were significantly higher in BG40 than in the control; whereas, there was no significant effect on the alkaline phosphatase level. Among serum immune activity, activities of lysozyme, the alternative complement pathway, and IgM were significantly higher in BG40. Phagocytic, and superoxide dismutase (SOD) activities were higher (P < 0.05) in BG30–BG50. Serum ALT, AST, and MDA levels were lower in BG40 than in the control (P < 0.05). Intestinal enzymatic activities were enhanced in BG40 and BG50 (P < 0.05), except for lipase in BG50. Gene expression analysis revealed that the mRNA expressions of antioxidant genes (SOD, GPx, and Nrf2), an anti-inflammatory gene (IL-10), and IκBα were significantly upregulated in BG40. Conversely, the pro-inflammatory gene IL-1β and the signaling molecule NF-κB p65 were downregulated in BG40 and BG50, respectively. BG supplementation had no significant effect on TNF-α, TLR22, or HSP70 mRNA expressions. Moreover, fish in BG40 exhibited the highest relative post-challenge survival (67.74%) against Aeromonas hydrophila infection. These results suggested that dietary supplementation with BG leaves at 40 g/kg can significantly improve the growth performance, immune responses, and disease resistance of C. carpio. BG leaves are a promising food additive for carp in aquaculture.

Rat Mucosal Immunity following an Intensive Chronic Training and an Exhausting Exercise: Effect of Hesperidin Supplementation

Stressful situations such as a high-intensity exercise or exhausting training programs can act as immune disruptors leading to transitory immunodepression status, which can be accompanied by alterations of the gastrointestinal functions. Hesperidin intake has demonstrated ergogenic activity and is able to influence the intestinal ecosystem and immunity. We aimed to investigate the effect of hesperidin consumption in rats submitted to an intense training and a final exhaustion test, focusing on the functionality of the intestinal immune system and on the cecal microbiota. Rats, supplemented or not with hesperidin, were intensively trained on a treadmill for 5 weeks. Samples were obtained 24 h after a regular training session, and immediately and 24 h after a final exhaustion test. Cecal microbiota and composition and function of mesenteric lymph node (MLN) lymphocytes and mucosal immunoglobulin A (IgA) were determined. Results showed that chronic intense exercise followed by an exhausting test induced changes in the intestinal immune compartment such as the distribution and function of MLN lymphocytes. Although the hesperidin supplementation did not prevent these alterations, it was able to enhance IgA synthesis in the intestinal compartment. This could be important in enhancing the immune intestinal barrier in this stressful situation.