Levels Of Specific IgG Antibodies Research Articles

Association of Helicobacter pylori specific IgG antibody with serum magnesium levels in peritoneal dialysis patients

Introduction: Few studies have reported the relationship between serum magnesium and Helicobacter pylori infection in chronic kidney disease (CKD) and patients receiving dialysis. Objectives: In this study, we aimed to test, the relationship between serum magnesium (Mg) level and H. pylori infection in CKD patients receiving peritoneal dialysis. Patients and methods: Around 40 patients were evaluated through the study. Serum magnesium levels and H. pylori specific IgG antibody levels were assessed. Results: The mean serum magnesium level was 3.00 ± 0.36 mg/dL. No significant difference was seen in serum Mg level between positive and negative groups of H. pylori. No correlations were reported between H. pylori IgG titers with age, serum Mg, Ca, P, parathyroid hormone (PTH), vitamin D, albumin, urea, creatinine (Cr) and plasma hemoglobin (P>0.05). Conclusion: In this study no correlation between serum magnesium levels and H. pylori specific IgG antibody was detected. We believe that this is the first study evaluating the relationship between serum magnesium level and H. pylori infection in peritoneal dialysis patients. More and larger clinical investigations are required to consider the conflicting results of studies regarding the association of serum magnesium and H. pylori in patients undergoing dialysis.

Decision tree and random forest models for outcome prediction in antibody incompatible kidney transplantation

Clinical datasets are commonly limited in size, thus restraining applications of Machine Learning (ML) techniques for predictive modelling in clinical research and organ transplantation. We explored the potential of Decision Tree (DT) and Random Forest (RF) classification models, in the context of small dataset of 80 samples, for outcome prediction in high-risk kidney transplantation. The DT and RF models identified the key risk factors associated with acute rejection: the levels of the donor specific IgG antibodies, the levels of IgG4 subclass and the number of human leucocyte antigen mismatches between the donor and recipient. Furthermore, the DT model determined dangerous levels of donor-specific IgG subclass antibodies, thus demonstrating the potential of discovering new properties in the data when traditional statistical tools are unable to capture them. The DT and RF classifiers developed in this work predicted early transplant rejection with accuracy of 85%, thus offering an accurate decision support tool for doctors tasked with predicting outcomes of kidney transplantation in advance of the clinical intervention.

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand

ABSTRACTBackground: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident.Methods: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0–5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression.Results: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05).Conclusions: The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or stool excretion following 3 doses of RV3-BB Rotavirus Vaccine administered using either a neonatal or infant schedule in New Zealand infants.

Resistance to Chronic Toxoplasma gondii Infection Induced by a DNA Vaccine Expressing GRA16.

Toxoplasma gondii can infect all warm-blooded animals including human beings. T. gondii dense granule protein 16 (TgGRA16) as a crucial virulence factor could modulate the host gene expression. Here, a DNA vaccine expressing TgGRA16 was constructed to explore the protective efficacy against T. gondii infection in Kunming mice. The immune responses induced by pVAX-GRA16 were also evaluated. Mice immunized with pVAX-GRA16 could elicit higher levels of specific IgG antibody and strong cellular response compared to those in controls. The DNA vaccination significantly increased the levels of cytokines (IFN-γ, IL-2, IL-4, and IL-10) and the percentages of CD4+ and CD8+ T cells in mice. After lethal challenge, mice immunized with pVAX-GRA16 (8.4 ± 0.78 days) did not show a significant longer survival time than that in controls (7.1 ± 0.30 days) (p > 0.05). However, in chronic toxoplasmosis model (administration of 10 brain cysts of PRU strain orally), numbers of tissue cysts in mice immunized with pVAX-GRA16 were significantly reduced compared to those in controls (p < 0.05) and the rate of reduction could reach 43.89%. The results indicated that the TgGRA16 would be a promising vaccine candidate for further development of effective epitope-based vaccines against chronic T. gondii infection in mice.

Immunogenicity and protective efficacy of a subunit vaccine SHP/TMD consisting of multi-stage antigens against Mycobacterium tuberculosis infection

Objective To construct a fusion protein SHP of subunit vaccine containing multi-stage antigens, and to confirm the immunogenicity and protective effect of SHP through M. tb infected Chinese population and C57BL/6 mice model. Methods Rv0577(secreted by replicating bacilli), Rv2623(expressed in dormant bacilli) and Rv3478(from PE/PPE family) were selected and to construct fusion protein SHP, WBIA(based on TB-IGRA) was performed to detect the specific concentration of IFN-γ stimulated from peripheral-blood lymphocyte of Chinese M. tb infections and non-infections.C57BL/6 mice were immunized(s.c.) with SHP emulsified in the adjuvant TMD.Nine weeks after immunized, SHP-specific antibody titers(IgG, IgG1, IgG2a), as well as the levels of Th1 cytokines by splenic lymphocytes stimulated with SHP and the mRNA expression levels of molecules in the lung of vaccinated mice were detected.Four weeks after challenge by M. tb H37Rv, the protective efficacy of SHP/TMD was evaluated. Results Recombinant plasmid pET30b-SHP and subgroups were constructed and expressed successfully, which stimulated statistically higher levels of IFN-γ in M. tb infected Chinese subjects than in healthy donors[SHP stimulated IFN-γ levels in infected and healthy groups were (1 420.0±253.9)pg/mL and (236.1±95.1)pg/mL, t=2.063, P<0.01]. SHP/TMD induced higher levels of specific IgG, IgG2a and IgG1 antibodies, and the ratio of IgG2a/IgG1 indicated that SHP/TMD mainly induced the Th1-type cell-mediated immune response.Meanwhile, SHP/TMD induced statistically higher levels of specific IFN-γ, TNF-α and IL-2 from splenic lymphocytes, also the mRNA expression levels of IFN-γ, TNF-α and iNOS from the lung.Moreover, SHP/TMD group resulted in the significant reduction of bacterial load in the lung and spleen organ(the reduction of bacterial load of SHP/TMD in comparison of TMD group was 1.03 log, F=1518, P<0.05), as well as lessened inflammation in alveolar tissue. Conclusion Based on the predominant antigens expressed during multi stages which can be recognized by T cells of M. tb infections from China, a subunit vaccine SHP/TMD was constructed.SHP/TMD can provide significant protective efficacy against acute infection of M. tb, which is mainly attributed to the SHP-specific CD4+ Th1-type cell immune response. Key words: Mycobacterium tuberculosis; Vaccine, subunit; BCG vaccine; Immunity

Edible Safety Assessment of Genetically Modified Rice T1C-1 for Sprague Dawley Rats through Horizontal Gene Transfer, Allergenicity and Intestinal Microbiota.

In this study, assessment of the safety of transgenic rice T1C-1 expressing Cry1C was carried out by: (1) studying horizontal gene transfer (HGT) in Sprague Dawley rats fed transgenic rice for 90 d; (2) examining the effect of Cry1C protein in vitro on digestibility and allergenicity; and (3) studying the changes of intestinal microbiota in rats fed with transgenic rice T1C-1 in acute and subchronic toxicity tests. Sprague Dawley rats were fed a diet containing either 60% GM Bacillus thuringiensis (Bt) rice T1C-1 expressing Cry1C protein, the parental rice Minghui 63, or a basic diet for 90 d. The GM Bt rice T1C-1 showed no evidence of HGT between rats and transgenic rice. Sequence searching of the Cry1C protein showed no homology with known allergens or toxins. Cry1C protein was rapidly degraded in vitro with simulated gastric and intestinal fluids. The expressed Cry1C protein did not induce high levels of specific IgG and IgE antibodies in rats. The intestinal microbiota of rats fed T1C-1 was also analyzed in acute and subchronic toxicity tests by DGGE. Cluster analysis of DGGE profiles revealed significant individual differences in the rats' intestinal microbiota.

Recombinant Bacillus subtilis spores for the delivery of Mycobacterium tuberculosis Ag85B-CFP10 secretory antigens

Tuberculosis continues to be a great cause of morbidity and mortality in different parts of the world. Unfortunately, the current BCG vaccine being administered is not fully protective against tuberculosis; therefore, there is a great need for alternate vaccines. With an aim to develop such vaccines, we have analyzed the utility of Bacillus subtilis spores for the expression of two major immunodominant antigens of Mycobacterium tuberculosis, Ag85B and CFP10. We created three recombinant B. subtilis strains to express a truncated fusion of Ag85B191-325 and CFP101-70 antigens (T85BCFP), either on the spore coat (MTAG1 strain) or in the cytosol of B. subtilis (MTAG 2 and MTAG 3 strains). Examination of spores isolated from these strains revealed successful expression of T85BCFP antigens on the spore coat of MTAG1 as well as in the cytosol of vegetatively grown cells of MTAG2 and MTAG3, indicating that spores can indeed express M. tuberculosis antigens. In vitro antigen presentation assays with spore-infected mouse bone marrow derived macrophages (BMDM) showed that all three recombinant spores could deliver these antigens to antigen presenting cells (APCs). Mice immunized with recombinant spores displayed significantly higher levels of Ag85B specific IFN-γ producing cells in the spleen than in mice immunized with wild-type (non-recombinant) spores. In addition, these mice showed relatively higher levels of Ag85B specific IgG antibodies in the serum in comparison to mice immunized with non-recombinant spores, thus providing additional evidence that recombinant spores can deliver these antigens in vivo. These results suggest that B. subtilis spores are ideal vehicles for antigen delivery and have great potential in the development of primary and booster vaccines against tuberculosis.

Exploitation of sub-micron cavitation nuclei to enhance ultrasound-mediated transdermal transport and penetration of vaccines

Inertial cavitation mediated by ultrasound has been previously shown to enable skin permeabilisation for transdermal drug and vaccine delivery, by sequentially applying the ultrasound then the therapeutic in liquid form on the skin surface. Using a novel hydrogel dosage form, we demonstrate that the use of sub-micron gas-stabilising polymeric nanoparticles (nanocups) to sustain and promote cavitation activity during simultaneous application of both drug and vaccine results in a significant enhancement of both the dose and penetration of a model vaccine, Ovalbumin (OVA), to depths of 500μm into porcine skin. The nanocups themselves exceeded the penetration depth of the vaccine (up to 700μm) due to their small size and capacity to ‘self-propel’. In vivo murine studies indicated that nanocup-assisted ultrasound transdermal vaccination achieved significantly (p<0.05) higher delivery doses without visible skin damage compared to the use of a chemical penetration enhancer. Transdermal OVA doses of up to 1μg were achieved in a single 90-second treatment, which was sufficient to trigger an antigen-specific immune response. Furthermore, ultrasound-assisted vaccine delivery in the presence of nanocups demonstrated substantially higher specific anti-OVA IgG antibody levels compared to other transdermal methods. Further optimisation can lead to a viable, safe and non-invasive delivery platform for vaccines with potential use in a primary care setting or personalized self-vaccination at home.

Response to pneumococcal polysaccharide vaccine in children with asthma, and children with recurrent respiratory infections, and healthy children

BackgroundTo analyse specific immune response to the 23-valent pneumococcal polysaccharide vaccine by measuring pneumococcal antibodies in children with asthma and with respiratory recurrent infection (RRI) as compared to healthy children. MethodsThe study included 60 children, divided into three groups: 20 with asthma, 20 with RRI, and 20 healthy controls. Post-vaccination specific IgG antibodies against 10 pneumococcal serotypes (S1, S3, S4, S5, S6B, S9V, S14, S18C, S19F, and S23F) contained in the 23-valent pneumococcal polysaccharide vaccine (PPV) were measured. A specific IgG concentration ≥1.3μg/mL was considered a protective response to the vaccine. For statistical analysis, levels of specific IgG antibodies against each of the 10 pneumococcal serotypes were compared across the three groups of children using the x2 test. ResultsAll of the children showed antipneumococcal antibody levels >1.3μg/mL for over 70% of the serotypes, considered within the normal range of response. Average IgG antibody levels and percentages of children protected were statistically comparable among the three groups studied. ConclusionThe asthmatic children without RRI had pneumococcal antibody levels and percentages of serotype-specific protection to PPV comparable to those of healthy children. Asthmatic children with recurrent infections should be evaluated for specific antibody deficiency (SAD). Because asthma patients are at high risk for invasive pneumococcal infections, it would be worthwhile to explore systematic administration of PPV in children over the age of two years who have not received a pneumococcal conjugate vaccine, considering the positive response to PPV reported here.

Yeast β-d-glucans induced antimicrobial peptide expressions against Salmonella infection in broiler chickens

The present study was designed to investigate the effects of yeast β-d-glucans (YG) on gene expression of endogenous β-defensins (AvBDs), cathelicidins (Cath) and liver-expressed antimicrobial peptide-2 (LEAP-2) in broilers challenged with Salmonella enteritidis (SE). 240 day-old Cobb male broilers were randomly assigned to 2×2 factorial arrangements of treatments with two levels of dietary YG (0 or 200mg/kg in diet) and two levels of SE challenge (0 or 1×109 SE at 7–9 days of age). The results showed SE infection reduced growth performance,and increased salmonella cecal colonization and internal organs invasion, increased concentration of intestinal specific IgA and serum specific IgG antibody, as compared to uninfected birds. SE challenge differentially regulated AvBDs, Caths and LEAP-2 gene expression in the jejunum and spleen of broiler chickens during the infection period. However, YG supplementation inhibited the growth depression by SE challenge, and further increased level of serum specific IgG and intestinal specific IgA antibody. Higher level of salmonella colonization and internal organs invasion in the SE-infected birds were reduced by YG. SE-induced differentially expression patterns of AMPs genes was inhibited or changed by YG. Results indicated YG enhance chicken's resistance to salmonella infection.

Immunity in the spleen and blood of mice immunized with irradiated Toxoplasma gondii tachyzoites.

Toxoplasma gondii infection induces a strong and long-lasting immune response that is able to prevent most reinfections but allows tissue cysts. Irradiated, sterilized T. gondii tachyzoites are an interesting vaccine, and they induce immunity that is similar to infection, but without cysts. In this study, we evaluated the cellular immune response in the blood and spleen of mice immunized with this preparation by mouth (v.o.) or intraperitoneally (i.p.) and analyzed the protection after challenge with viable parasites. BALB/c mice were immunized with three i.p. or v.o. doses of irradiated T. gondii tachyzoites. Oral challenge with ten cysts of the ME-49 or VEG strain at 90days after the last dose resulted in high levels of protection with low parasite burden in the immunized animals. There were higher levels of specific IgG, IgA and IgM antibodies in the serum, and the i.p. immunized mice had higher levels of the high-affinity IgG and IgM antibodies than the orally immunized mice, which had more high-affinity IgA antibodies. B cells (CD19(+)), plasma cells (CD138(+)) and the CD4(+) and CD8(+) T cell populations were increased in both the blood and spleen. Cells from the spleen of the i.p. immunized mice also showed antigen-induced production of interleukin-10 (IL-10), interferon gamma (IFN-γ) and interleukin 4 (IL-4). The CD4(+) T cells, B cells and likely CD8(+) T cells from the spleens of the i.p. immunized mice proliferated with a specific antigen. The protection was correlated with the spleen and blood CD8(+) T cell, high-affinity IgG and IgM and antigen-induced IL-10 and IL-4 production. Immunization with irradiated T. gondii tachyzoites induces an immune response that is mediated by B cells and CD4(+) and CD8(+) T cells, with increased humoral and cellular immune responses that are necessary for host protection after infection. The vaccine is similar to natural infection, but free of tissue cysts; this immunity restrains infection at challenge and can be an attractive and efficient model for vaccine development in toxoplasmosis.

Evaluation of humoral immune status in porcine epidemic diarrhea virus (PEDV) infected sows under field conditions.

Porcine epidemic diarrhea virus (PEDV) is an economically devastating enteric disease in the swine industry. The virus infects pigs of all ages, but it cause severe clinical disease in neonatal suckling pigs with up to 100% mortality. Currently, available vaccines are not completely effective and feedback methods utilizing PEDV infected material has variable success in preventing reinfection. Comprehensive information on the levels and duration of effector/memory IgA and IgG antibody secreting B cell response in the intestines and lymphoid organs of PEDV-infected sows, and their association with specific antibody levels in clinical samples such as plasma, oral fluid, and feces is important. Therefore, our goal in this study was to quantify PEDV specific IgA and IgG B cell responses in sows at approximately 1 and 6 months post-infection in commercial swine herds, including parity one and higher sows. Our data indicated that evaluation of both PEDV specific IgA and IgG antibody levels in the plasma and oral fluid (but not feces) samples is beneficial in disease diagnosis. PEDV specific B cell response in the intestine and spleen of infected sows decline by 6 months, and this associates with specific antibody levels in the plasma and oral fluid samples; but the virus neutralization titers in plasma remains high beyond 6 months post-infection. In conclusion, in sows infected with PEDV the presence of effector/memory B cell response and strong virus neutralization titers in plasma up to 6 months post-infection, suggests their potential to protect sows from reinfection and provide maternal immunity to neonates, but challenge studies are required to confirm such responses.

Engineering of the PapMV vaccine platform with a shortened M2e peptide leads to an effective one dose influenza vaccine

The emergence of highly virulent influenza strains and the risks of pandemics as well as the limited efficiency of the current seasonal vaccines are important public health concerns. There is a major need for new influenza vaccines that would be broadly cross-protective. The ectodomain of matrix protein 2 (M2e) is highly conserved amongst different influenza strains and could be used as a broad spectrum antigen. To overcome its low immunogenicity we have fused a short peptide epitope derived from the human consensus sequence of M2e (amino acids 6–14, EVETPIRNE) to the N-terminus of papaya mosaic virus coat protein. The fusion harboring coat proteins were assembled around a single stranded RNA into virus-like particles (PapMV-sM2e). The resulting PapMV-sM2e rod-shaped particle was stable and indistinguishable from regular PapMV particles. A single intramuscular immunization with PapMV-sM2e was sufficient to mount appreciable levels of CD4 dependent M2e specific total IgG and IgG2a antibody in mice sera. PapMV-sM2e proved to be self-adjuvanting since the addition of PapMV as an exogenous adjuvant did not result in significantly improved antibody titers. In addition, we confirmed the adjuvant property of PapMV-sM2e using the trivalent inactivated flu vaccine as antigen and demonstrated that the newly engineered nanoparticles areas efficacious as an adjuvant than the original PapMV nanoparticles. Upon infection with a sub-lethal dose of influenza, PapMV-sM2e vaccinated animals were completely protected from virus induced morbidity and mortality. Mice immunized with decreasing amounts of PapMV-sM2e and challenged with a more stringent dose of influenza virus displayed dose-dependent levels of protection. Seventy percent of the mice immunized once with the highest dose of PapMV-sM2e survived the challenged. The survival of the mice correlated mainly with the levels of anti-M2e IgG2a antibodies obtained before the infection. These results demonstrate that PapMV-sM2e can be an important component of a broadly cross-reactive influenza vaccine.

Immunogenic Activity of Secreted Protein-Based Compounds Staphylococcus aureus № 6

Difficulties in the therapy of infection, caused by S. aureus, depends on the resistance of staphylococci to antibiotics, proceeding to chronicity of the diseases and the development on that background the depression of innate immunity functions and decreasing of the host resistance to the infection. In spite of tremendous efforts of researchers, up to date there are no commercial antistaphylococcal vaccine the efficacy of which would be proved in the completed clinical trials. Aim: obtaining secreted protein-based substances of the S. aureus № 6 and investigation their immunogenicity. Material and methods. Secreted protein-based substances (SPS) were obtain as: «initial» – from the filtrates of the culture fluid of the S. aureus № 6, grown to the end of the exponential phase according to the technology described previously [9], and I SPS and II SPS – after the ion-exchange chromatography of the «initial» SPS on the columns with Q-Sepharose and DEAE-Sepharose. The level of specific IgG antibodies in sera of immunized rabbits and mice determined in ELISA, the immunogenic activity evaluated in experiments of active and passive protection from the challenge performed on BALB/с mice and also by the determination of the bacterial content in organs and in the test of abscesses formation in kidneys. Results. Investigated SBS possessed the antigenic activity (the level of specific IgG antibodies in sera of immunized animals increased 2.2 – 7.5 times compared to the control groups), that is favor of the activation of the adaptive immunity system and significant protective activity revealed in experiments of active (index of efficacy 2.63 – 4.28) and passive protection. The immunization of mice with the «initial» and II SPS led to significant decrease of the number of colonyforming units of S. aureus and formation of abscesses in kidneys of mice. It is evidently, that investigated SPS, influence on the severity of staphylococcal infection and possesses the therapeutic effect. Conclusion. The preformed complex analysis at the current stage allowed to reveal perspectives of the further study of «initial» and II SPS in pre-clinical trials, as candidates, possessing the high protective facilities, for including them in the drug composition for immune prophylaxis and immunotherapy of diseases, caused by S. aureus.

Abstract POSTER-TECH-1107: Primary platinum sensitivity in ovarian cancer and serum antibodies recognizing hypoxia-inducible factor 1-alpha and p53

Abstract Objective: Overexpression of hypoxia inducible factor 1-alpha (HIF-1α), a protein associated with apoptosis resistance, angiogenesis and metastasis, correlates with aberrant p53 protein accumulation in ovarian cancer. Humoral immunity to tumor-associated antigens in ovarian cancer has been associated with prognosis. We hypothesize that serum IgG antibodies recognizing HIF-1α and p53 in ovarian cancer patients could predict primary platinum response in ovarian cancer. Methods: Serum samples collected from ovarian cancer patients (n = 171) at the time of their initial surgery were analyzed by enzyme-linked immunosorbent assay for IgG antibodies to human recombinant HIF-1α and p53 proteins. The positive cut-off for each IgG antibody was derived at a serum level yielding highest hazard ratio of overall survival. Age, stage, grade, histology, neo-adjuvant therapy, surgical outcome, primary platinum response, and overall survival (OS) were correlated with serum IgG antibody levels. Results: Ovarian cancer patients were mostly stage III/IV (94%) with serous histology (85%), and the majority were optimally debulked (74%). Primary platinum sensitive patients (n = 116) had significantly higher IgG antibody levels than primary platinum resistant patients (n = 55) (median 0.83 µg/mL vs. 0.0 µg/mL, p = 0.001 for HIF-1α and median 6.37 µg/mL vs. 2.69 µg/mL, p =0.001 for p53). Humoral immune competence among cancer patients was not significantly different between primary platinum sensitive and resistant groups. Multivariate analysis of overall survival associated age and advanced stage with adverse survival, while elevated levels of serum HIF-1α IgG(≥ 0.32 µg/mL, HR = 0.57, p = 0.012) and p53 IgG (≥ 2.8 µg/mL, HR = 0.58, p = 0.024) were favorable prognostic factors. Multivariate logistic regression revealed HIF-1α and p53 -specific IgG antibody levels to be independent predictors of primary platinum sensitivity (OR=3.28, 95% CI 1.55 – 6.94, p = 0.002 for HIF-1α and OR = 4.61, 95% CI 2.11 – 10.1, p &amp;lt; 0.001 for p53). A model predicting sensitivity to adjuvant platinum-based treatment that includes only 2 factors, HIF-1α and p53 IgG antibody levels, yields an AUC = 0.710 and bests one containing 6 clinical variables (age, stage, histology, grade, surgical outcome, neoadjuvant treatment) which reaches AUC = 0.688. Our selected model of 4 factors: HIF-1α and p53 IgG antibody levels, stage, and neoadjuvant treatment, achieves comparable discrimination (AUC = 0.797) with a comprehensive model of 2 serum biomarkers and 6 clinical factors (AUC = 0.802). Conclusion: Viable strategies for the primary treatment of ovarian cancer have expanded beyond intravenous carboplatin and paclitaxel every 3 weeks after primary cytoreductive surgery to include alternate dosing, neoadjuvant chemotherapy, intraperitoneal administration, and the addition of novel biologic agents such as bevacizumab, yet there are no biomarkers to guide which patients derive the most benefit from these treatments, despite significant differences in their toxicities, cost, and associated quality of life. The ability of serum antibodies recognizing tumor associated antigens at time of diagnosis to identify patients most likely to achieve a durable response to platinum based chemotherapy may allow the selection of primary treatment to be optimized and improve response rates. Citation Format: M. D. Dao, K. J. Ovenell, K. J. Agnew, E. M. Swisher, B. A. Goff, M. L. Disis, J. B. Liao. Primary platinum sensitivity in ovarian cancer and serum antibodies recognizing hypoxia-inducible factor 1-alpha and p53 [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-TECH-1107.

Fc receptor γ chain plays a critical role in lung viral clearance and reducing vaccine-enhanced disease in mice immunized with respiratory syncytial virus vaccines (VAC9P.1063)

Abstract Vaccine-enhanced respiratory disease (ERD) is well-known for respiratory syncytial virus (RSV) after vaccination with formalin inactivated RSV (FI-RSV). Induction of Th2 type immune responses and deposition of immune complexes have been suggested to be possible mechanisms. We hypothesized that Fc receptor γ chain (FcRγ) would play a role in conferring protection against RSV after vaccination and that priming with Th1 inducing vaccine would prevent ERD. Virus-like particles presenting RSV fusion protein (F VLP) were found to induce Th1 type immune responses. Wild type (WT) mice and FcRγ KO mice were immunized with FI-RSV or primed with F VLP followed by FI-RSV boost (F VLP/FI-RSV). RSV specific serum IgG and isotype antibody levels were similar in both WT and FcRγ KO mice after RSV vaccination. However, F VLP/FI-RSV FcRγ KO mice showed lower levels of RSV neutralizing antibody titers and IFN-γ secreting CD8+ T cells, higher lung viral titers and more body weight loss compared to F VLP/FI-RSV WT mice. Heterologous F VLP/FI-RSV immunization induced Th1 type humoral and cellular immune responses, no overt sign of ERD in the bronchoalveolar lavage airways in both WT and FcRγ KO mice compared to homologous FI-RSV immunization. The results in this study support a critical role of FcRγ in lung viral clearance and diminishing ERD. More importantly, a strategy of priming with Th1 inducing vaccine might be a promising approach to induce protection against RSV and to prevent ERD.

The combination of the aliphatic diamine AA0029 in ADAD vaccination system with a recombinant fatty acid binding protein could be a good alternative for the animal schistosomiasis control

Fatty acid binding proteins (FABP) from Fasciola hepatica have demonstrated immune cross-protection against schistosomes. The present study was conducted to develop a new formulation of the recombinant FABP rFh15 with the synthetic immunomodulator AA0029 in the adjuvant adaptation (ADAD) vaccination system and to evaluate its ability to induce immune response and protection against the challenge with Schistosoma bovis cercariae. Immunization of BALB/c mice showed high levels of TNFα, IFNγ, interleukin (IL)-2, IL-6, and IL-4 in splenocyte supernatant culture and also high levels of serum specific anti-rFh15 IgG, IgG1, IgG2a IgE and IgM antibodies suggesting a mixed Th1/Th2 immune response. Using this approach, high levels of protection against experimental challenge with S. bovis cercariae were observed in the mouse and hamster models. A marked reduction up to 64% in worm burden, as well as in the number of eggs retained in liver (66%) and intestine (77%) and hepatic lesions (42%), was achieved in vaccinated BALB/c mice. Golden hamsters vaccinated and challenged in similar conditions had reductions in recovered worms (83%), liver eggs (90%), intestine eggs (96%), liver lesions (56%) and worm fecundity (48–80%). These data suggest that formulation of rFh15 in the ADAD vaccination system using the AA0029 immunomodulator could be a good option to drive an effective immunological response against schistosomiasis.

Screening diagnostic candidates for schistosomiasis from tegument proteins of adult Schistosoma japonicum using an immunoproteomic approach.

BackgroundSchistosomiasis is one of the world’s most prevalent zoonotic diseases and a serious worldwide public health problem. Since the tegument (TG) of Schistosoma japonicum is in direct contact with the host and induces a host immune response against infection, the identification of immune response target molecules in the schistosome TG is crucial for screening diagnostic antigens for this disease.Methodology/Principal FindingsIn this study, an immunoproteomics approach used TG proteins as screening antigens to identify potential diagnostic molecules of S. japonicum. Ten spots corresponding to six proteins were identified that immunoreacted with sera from S. japonicum-infected rabbits but not sera from uninfected rabbits and their specific IgG antibody levels declined quickly after praziquantel treatment. Recombinant phosphoglycerate mutase (PGM) and UV excision repair protein RAD23 homolog B (RAD23) proteins were expressed and their diagnostic potential for schistosomiasis was evaluated and compared with schistosome soluble egg antigen (SEA) using ELISA. The results showed high sensitivity and specificity and low crossreactivity when rSjPGM-ELISA and rSjRAD23-ELISA were used to detect water buffalo schistosomiasis. Moreover, antibodies to rSjPGM and rSjRAD23 might be short-lived since they declined quickly after chemotherapy.Conclusion/SignificanceTherefore, the two schistosome TG proteins SjPGM and SjRAD23 were identified as potential diagnostic markers for the disease. The two recombinant proteins might have the potential to evaluate the effectiveness of drug treatments and for distinguishing between current and past infection.

The Anopheles gambiae cE5 salivary protein: a sensitive biomarker to evaluate the efficacy of insecticide-treated nets in malaria vector control

Evaluation of vector control is crucial for improving malaria containment and, according to World Health Organization, new complementary indicators would be very valuable. In this study the IgG response to the Anopheles-specific cE5 salivary protein was tested as a tool to evaluate the efficacy of insecticide-treated nets in reducing human exposure to malaria vectors. Sera collected during a longitudinal study carried out in Angola, and including entomological and parasitological data, were used to assess the IgG response to the Anopheles gambiae cE5 in both children and adults, before and after the application of insecticide-treated nets. Seasonal fluctuation of specific IgG antibody levels according to exposure was only found in children (up to ≈14 years old) whose anti-cE5 IgG response dropped after bed nets installation. These results were fully consistent with previous findings obtained with the same set of sera and indicating a substantial reduction of human-vector contact shortly after nets implementation. Overall, children IgG response to the cE5 protein appeared a very sensitive biomarker, which allowed for the detection of even weak exposure to Anopheles bites, indicating it may represent a reliable additional tool to evaluate the efficacy of vector control interventions.

Recurring Outbreaks of an Infection Apparently Targeting Immune Function, and Consequent Unprecedented Growth in Medical Admission and Costs in the United Kingdom: A Review

Background: The National Health Service (NHS) in the UK has been beset by unprecedented growth in emergency admissions to hospital which are specifically medical in nature, while surgical and trauma admissions are only showing the level of low growth expected from demographic change, or what is called the ageing population. There has never been an adequate explanation for this dichotomy. An Infectious Basis: The proposed infectious basis rests upon the observation that growth in medical admissions occurs in spurts which occur approximately five years apart, albeit three years between spurts have also been observed during the 1990’s. It is these spurts which are driving the long-term growth, rather than the relatively minor growth which occurs in the interval between the spurts. These periods of high growth are characterized by spikes in all-cause mortality, and typically result in a 15% increases in admissions to the medical group of specialties. However much higher growth is seen for particular conditions/diagnoses which appear to have a common Review Article Jones; BJMMR, 6(8): 735-770, 2015; Article no.BJMMR.2015.251 736 immune function basis via infection, inflammation and autoimmunity. These outbreaks can be seen across Europe, and the last three outbreaks commenced around Mar-02, Mar-05 and Mar-10 with subsequent spread over the next two years. The middle of these three outbreaks had the lowest increase in deaths and medical admissions. Implications: There is now an overwhelming body of evidence pointing to a recurring series of infectious-like events. In the UK, the 2012/2013 outbreak led to 45,000 extra deaths while across the 27 EU countries, each outbreak appears to result in somewhere in excess of 467,000 deaths. In Europe, the outbreaks tend to occur earlier in Denmark, Romania, Bulgaria and Slovakia, while they tend to occur later in the UK, Belgium, Greece and Slovenia. Emphasis now needs to switch toward clinical studies which screen the population for changes in the levels of specific IgM and IgG antibodies against a range of potential candidate organisms, and post mortem examination of the tissues of persons who die from a particular range of conditions such as neurological disorders including dementia and Alzheimer’s; respiratory and gastrointestinal tract diseases, and cardio/vascular conditions. Conclusion: This new disease has the potential to be a highly disruptive discovery involving changes in fundamental health care policy, and our understanding of the role of immune function in the exacerbation of a range of common medical conditions.