Human Milk Oligosaccharide 3'-GL Improves Influenza-Specific Vaccination Responsiveness and Immunity after Deoxynivalenol Exposure in Preclinical Models.
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ABSTRACT:
SUBMITTER: Toutounchi NS
PROVIDER: S-EPMC8466816 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:Human milk is uniquely suited to provide optimal nutrition and immune protection to infants. Human milk oligosaccharides are structural complex and diverse consisting of short chain and long chain oligosaccharides typically present in a 9:1 ratio. 2'-Fucosyllactose (2'FL) is one of the most prominent short chain oligosaccharides and is associated with anti-infective capacity of human milk. Aim:To determine the effect of 2'FL on vaccination responsiveness (both innate and adaptive) in a murine influenza vaccination model and elucidate mechanisms involved. Methods:A dose range of 0.25-5% (w/w) dietary 2'FL was provided to 6-week-old female C57Bl/6JOlaHsd mice 2?weeks prior primary and booster vaccination until the end of the experiment. Intradermal (i.d.) challenge was performed to measure the vaccine-specific delayed-type hypersensitivity (DTH). Antigen-specific antibody levels in serum as well as immune cell populations within several organs were evaluated using ELISA and flow cytometry, respectively. In an ex vivo restimulation assay, spleen cells were cocultured with influenza-loaded bone marrow-derived dendritic cells (BMDCs) to study the effects of 2'FL on vaccine-specific CD4+ and CD8+ T-cell proliferation and cytokine secretions. Furthermore, the direct immune regulatory effects of 2'FL were confirmed using in vitro BMDCs T-cell cocultures. Results:Dietary 2'FL significantly (p?<?0.05) enhanced vaccine specific DTH responses accompanied by increased serum levels of vaccine-specific immunoglobulin (Ig) G1 and IgG2a in a dose-dependent manner. Consistently, increased activation marker (CD27) expression on splenic B-cells was detected in mice receiving 2'FL as compared to control mice. Moreover, proliferation of vaccine-specific CD4+ and CD8+ T-cells, as well as interferon-? production after ex vivo restimulation were significantly increased in spleen cells of mice receiving 2'FL as compared to control mice, which were in line with changes detected within dendritic cell populations. Finally, we confirmed a direct effect of 2'FL on the maturation status and antigen presenting capacity of BMDCs. Conclusion:Dietary intervention with 2'FL improves both humoral and cellular immune responses to vaccination in mice, which might be attributed in part to the direct effects of 2'FL on immune cell differentiation.
| S-EPMC5854647 | biostudies-literature
Project description:Oral vaccination would provide an easy and safe measure to prevent infectious diseases by facilitating mass immunization. We investigated the feasibility of oral vaccination with inactivated whole influenza virus (A/PR8/34). Oral vaccination of mice induced high levels of serum IgG and IgA antibodies specific to the homologous virus (A/PR8) as well as cross reactive to heterologous (A/California/04/09) and heterosubtypic viruses (A/Philippines/2/82). IgG1 isotype antibodies were found to be induced at significantly higher levels than IgG2a antibodies. These antibodies induced by oral vaccination exhibited hemagglutination inhibition activities. High levels of both IgG and IgA antibodies were induced in vagina and lungs. Mucosal IgA antibodies were also elicited in other sites including saliva, urine, and fecal samples. Orally vaccinated mice were completely protected against challenge with homologous or heterologous viruses, and partially protected against heterosubtypic virus. Importantly, high recall antibody secreting cell (ASC) responses were induced in spleen, indicating the generation of memory B cells by oral vaccination. The present study therefore presents new findings of cross-reactive antibodies at systemic and diverse mucosal sites, recall antibody responses, and cross-protective efficacies by oral vaccination, thus supporting a proof-of-concept that oral delivery of vaccines can be developed as an effective vaccination route.
| S-EPMC5555299 | biostudies-other
Project description:(1) Background: The influenza virus continues to cause significant annual morbidity and mortality. The overall efficacy of seasonal influenza vaccination is suboptimal, which is partly due to host immune factors. The effects of imprinting and repeated seasonal influenza vaccination were investigated to assess for immune factors and mechanisms that impact influenza vaccine responses. (2) Methods: Twenty participants were enrolled into a prospective pilot study based on birth cohort and seasonal influenza immunization history. Immunologic parameters were assessed over a six-month period after the seasonal influenza vaccine was administered. (3) Results: There was no significant imprinting effect, as measured by hemagglutination inhibition (HAI) fold change, HAI geometric mean titer (GMT) for Day 29 or Day 180 post-vaccination and antigen- specific antibody-secreting cells (ASC) for Day 8 post-vaccination. Individuals who had minimal prior seasonal influenza vaccination had a higher magnitude ASC response and a higher HAI fold change post-vaccination than individuals who were repeatedly vaccinated. (4) Conclusions: Repeated seasonal influenza vaccination resulted in a decreased fold change of the immune response, although individuals in this cohort tended to have high HAI titers at baseline that persisted after vaccination. Imprinting effects were not observed in this cohort. These host immune factors should be considered in the development of universal influenza vaccines. ClinicalTrials.gov Identifier: NCT03686514.
| S-EPMC7712189 | biostudies-literature
Project description:Influenza vaccination often results in a large percentage of low responders, especially in high-risk groups. As a first line of defense, natural killer (NK) cells play a crucial role in the fight against infections. However, their implication with regard to vaccine responsiveness is insufficiently assessed. Therefore, this study aimed at the validation of essential NK cell features potentially associated with differential vaccine responsiveness with a special focus on NKG2C- and/or CD57-expressing NK cells considered to harbor memory-like functions. To this end, 16 healthy volunteers were vaccinated with an adjuvanted pandemic influenza vaccine. Vaccine responders and low responders were classified according to their hemagglutination inhibition antibody titers. A majority of responders displayed enhanced frequencies of NKG2C-expressing NK cells 7- or 14-days post-vaccination as compared to low responders, whereas the expression of CD57 was not differentially modulated. The NK cell cytotoxic potential was found to be confined to CD56dimCD16+ NKG2C-expressing NK cells in the responders but not in the low responders, which was further confirmed by stochastic neighbor embedding analysis. The presented study is the first of its kind that ascribes CD56dimCD16+ NKG2C-expressing NK cells a crucial role in biasing adaptive immune responses upon influenza vaccination and suggests NKG2C as a potential biomarker in predicting pandemic influenza vaccine responsiveness.
| S-EPMC7349951 | biostudies-literature
Project description:BackgroundSchool-located influenza vaccination (SLV) programs can efficiently immunize large numbers of school-aged children. We evaluated the impact of SLV on laboratory-confirmed influenza and absenteeism.MethodsActive surveillance for influenza-like illness (ILI) was conducted on 4455 children in 4 SLV intervention and 4 control elementary schools (grades K-6) matched for sociodemographic characteristics during the 2010-2011 influenza season in Los Angeles County, California. Combined nose/throat swabs were collected from febrile children with ILI at presentation to the school nurse or during absenteeism.ResultsIn SLV schools, 26.9%-46.6% of enrolled students received at least 1 dose of either inactivated or live attenuated influenza vaccine compared with 0.8%-4.3% in control schools. Polymerase chain reaction for respiratory viruses (PCR) was performed on 1021 specimens obtained from 898 children. Specimens were positive for influenza in 217 (21.3%), including 2009 H1N1 (30.9%), H3 (9.2%), and B (59.9%). Children attending SLV schools, regardless of vaccination status, were 30.8% (95% confidence interval, 10.1%-46.8%) less likely to acquire influenza compared with children at control schools. Unvaccinated children were indirectly protected in the school with nearly 50% vaccination coverage compared with control schools (influenza rate, 27.1 vs 60.0 per 1000 children; P = .023). Unvaccinated children missed more school days than vaccinated children (4.3 vs 2.8 days per 100 school days; P < .001).ConclusionsVaccination of at least a quarter of the school population resulted in decreased influenza rates and improved school attendance. Herd immunity for unvaccinated children may occur in schools with vaccination coverage approaching 50%.
| S-EPMC4155443 | biostudies-literature
Project description:Protective antibody immunity against the influenza A virus wanes in 2-7 years due to antigenic drift of the virus' surface proteins. The duration of immune protection is highly variable because antigenic evolution of the virus is irregular. Currently, the variable nature of the duration of immunity has had little attention in analyses of the impact of vaccination, including cost-effectiveness studies.We developed a range of mathematical transmission models to investigate the effect of variable duration of immunity on the size of seasonal epidemics. The models range from simple conceptual to more realistic, by distinguishing between infection- versus vaccination-induced immunity, by inclusion of primary vaccine failure, by assuming a leaky vaccine, and by the inclusion of age-dependent contact patterns.We show that annual variation in the duration of immunity causes large variation in the size of epidemics, and affects the effectiveness of vaccination. Accumulation of susceptible individuals in one or more mild seasons results in a disproportionately large outbreak in a subsequent season. Importantly, variation in the duration of immunity increases the average infection attack rate when the vaccination coverage is around the outbreak threshold. Specifically, in a tailored age-stratified model with a realistic reproduction number (R 0 = 1.4) and vaccination coverage of 25%, we find that the attack rate in unvaccinated children (<10 years old) is negligible if the duration of immunity is constant, while on average 2.8% (2.5-97.5% percentiles: 1.8-4.1%) of the children are infected if the duration of immunity is variable. These findings stem from the buildup of susceptibility over multiple seasons by waning of immunity, and the nonlinear relation between susceptibility and infection attack rates.The models illustrate that variation in the duration of immunity impacts the long-term effectiveness of vaccination, and that vaccine effectiveness cannot be judged for each year in isolation. Our findings have implications for vaccination strategies that aim to maximize the vaccination coverage while extending the age range of persons eligible for vaccination.
| S-EPMC5606000 | biostudies-other
Project description:Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2)) generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4(+)IL-17A(+)TNFα(+)). Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development.
| S-EPMC3900655 | biostudies-literature
Project description:We estimated the effect of oligosaccharide supplementation and feed restriction on calves. The study was divided into two experimental periods of 28 days each with 20 crossbred calves that had initial body weight of 37 Kg and housed in individual pens. The animals were split in four experimental groups: animals fed 6 L milk/day (CON) in the two periods, animals fed milk restricted (3 L milk/day) in the first period and followed by CON feeding in the second period (RES), animals receiving supplementation of 5 g/day of mannanoligosaccharide (MOS) and animals receiving supplementation of 5 g/day mannan and frutoligosaccharide (MFOS). At the end of the study, all the animals were slaughtered. The average weight gain was lower in the restricted group when compared with CON and MFOS groups in the first period (P < 0.05) and there were no difference among the groups in the second period. Animals supplemented with MOS showed a significant increases in jejunal villus height and rumen papillae, which were not observed for MFOS group (P < 0.05) compared with RES and CON groups. There were no difference in ghrelin and leptin levels among treatments during periods 1 and 2 (P > 0.05). Also, the expression of ghrelin receptors in the paraventricular region of the hypothalamus did not differ among groups. We conclude that milk restriction during the first weeks of life in calves resulted in compensatory gain and did not modify the hormonal profile and expression of the ghrelin receptor in the hypothalamus. Moreover, a prebiotic supplementation changed the development of intestinal and ruminal epithelium.
| S-EPMC6438680 | biostudies-literature
Project description:BackgroundConsumption of dairy products reduces risk of type 2 diabetes. Milk proteins and fats exhibit anti-diabetic properties but milk sugars have been studied little in this context. Galactose from milk lactose is readily converted to glycogen in the liver but its effects on insulin sensitivity have not been assessed. Prebiotic oligosaccharides from milk alter gut microbiota and can thereby influence host metabolism. Our objective was to assess the effect on insulin sensitivity of dietary galactose compared to glucose and fructose, and fermentable galacto-oligosaccharides compared to non-fermentable methylcellulose.MethodsDiets containing 15% of dry matter from glucose, fructose, galactose, galacto-oligosaccharides, or methylcellulose were fed to 36 rats per diet for 9 weeks. Hyperinsulinemic-euglycemic clamps with [3-3H]glucose infusion and a steady-state 2-[1-14C]deoxyglucose bolus injection were used to assess insulin sensitivity and glucose uptake indices. Tissue was collected in fed, fasted and fasted, insulin-stimulated states.ResultsGalactose increased glucose infusion rate during the clamp by 53% and decreased endogenous glucose production by 57% compared to glucose and fructose. Fed-state hepatic glycogen content was greater with galactose compared to glucose and fructose, consistent with a potentiation of the insulin effect on glycogen synthase by dephosphorylation. Galactose decreased the fecal Firmicutes:Bacteroidetes ratio while galacto-oligosaccharides increased abundance of fecal Bifidobacterium spp. 481-fold compared to methylcellulose, and also increased abundance of Lactobacillus spp. and Bacteroidetes. Galacto-oligosaccharides did not affect glucose infusion rate or endogenous glucose production during basal or clamp periods compared to methylcellulose.ConclusionsGalactose at 15% of daily intake improved hepatic insulin sensitivity in rats compared to glucose and fructose. Galactose caused an increase in fed-state hepatic glycogen content and a favourable shift in gut microbial populations. Intake of galacto-oligosaccharides improved the gut microbial profile but did not improve insulin sensitivity.
| S-EPMC5313224 | biostudies-literature
Project description:Split inactivated influenza vaccines remain one of the primary preventative strategies against severe influenza disease in the population. However, current vaccines are only effective against a limited number of matched strains. The need for broadly protective vaccines is acute due to the high mutational rate of influenza viruses and multiple strain variants in circulation at any one time. The neuraminidase (NA) glycoprotein expressed on the influenza virion surface has recently regained recognition as a valuable vaccine candidate. We sought to broaden the protection provided by NA within the N1 subtype by computationally engineering consensus NA sequences. Three NA antigens (NA5200, NA7900, NA9100) were designed based on sequence clusters encompassing three major groupings of NA sequence space; (i) H1N1 2009 pandemic and Swine H1N1, (ii) historical seasonal H1N1 and (iii) H1N1 viruses ranging from 1933 till current times. Recombinant NA proteins were produced as a vaccine and used in a mouse challenge model. The design of the protein dictated the protection provided against the challenge strains. NA5200 protected against H1N1 pdm09, a Swine isolate from 1998 and NIBRG-14 (H5N1). NA7900 protected against all seasonal H1N1 viruses tested, and NA9100 showed the broadest range of protection covering all N1 viruses tested. By passive transfer studies and serological assays, the protection provided by the cluster-based consensus (CBC) designs correlated to antibodies capable of mediating NA inhibition. Importantly, sera raised to the consensus NAs displayed a broader pattern of reactivity and protection than naturally occurring NAs, potentially supporting a predictive approach to antigen design.
| S-EPMC6265323 | biostudies-literature