Journal: Clinical and vaccine immunology : CVI
Background:With continuing occurrence of varicella despite of increasing vaccine coverage for the past 20 years, a case-based study, a case-control study, and an immunogenicity and safety study were conducted to address the impact of varicella vaccination in Korea.Subjects and methods:Varicella patients under the age of 16 years were enrolled for the case-based study. For the case-control study, varicella patients between 12 months and 15 years of age were enrolled with one control matched for each patient. For the immunogenicity and safety study, otherwise healthy children aged from 12 to 24 months were immunized with Suduvax (Green Cross, Korea). FAMA VZV antibody was measured before and 6weeks after immunization.Results:In the case-based study, the median age of the patients was 4 years. Among 152 cases aged 1-15 years, 139 children received varicella vaccine and all had breakthrough infections. Clinical courses were not ameliorated in vaccinated patients, but more vaccinated patients received outpatient rather than inpatient care. In the case-control study, the adjusted overall effectiveness of varicella vaccination was 54%. In the immunogenicity and safety study, the seroconversion rate and geometric mean titer for FAMA antibody were 76.67% and 5.31.Conclusions:Even with increasing varicella vaccine uptake, we illustrate no upward age-shift in the peak incidence, a high proportion of breakthrough disease, almost no amelioration in disease presentation by vaccination, and insufficient Immunogenicity of domestic varicella vaccine. There are needs to improve the varicella vaccine used in Korea.
Celiac disease (CD) is an autoimmune disorder that occurs in genetically susceptible individuals of all ages and is triggered by immune response to gluten and related proteins. The disease is characterized by the presence of HLA-DQ2 and/or DQ8 haplotypes, diverse clinical manifestations, gluten-sensitive enteropathy and production of several autoantibodies of which endomysial, tissue transglutaminase and deamidated gliadin peptide antibodies are considered specific. Although anti-reticulin antibodies (ARA) have historically been used in the evaluation of CD, these assays lack optimal sensitivities and specificities for routine diagnostic use. This review highlights the advances in CD-specific serologic testing and the rationale for eliminating ARA from CD evaluation consistent with recommendations for diagnosis.
The therapeutic effects of a controlled parasitic nematode infection on the course of inflammatory bowel disease (IBD) have been demonstrated in both animal and human models. However the inability of individual well characterized nematode proteins to recreate these beneficial effects has limited the application of component immunotherapy to human disease. The nematodes that cause chronic human lymphatic filariasis, Brugia malayi and Wuchereria bancrofti, are among the parasites that induce immune suppression. Filarial lymphatic pathology has been shown to involve NFk B pathway dependent production of vascular endothelial growth factor (VEGF), and stimulation of VEGF expression has also been reported by interleukin 8 (IL8) via NFkB pathways. Previously we have shown that the filarial asparaginyl-tRNA synthetase (rBmAsnRS) interacts with IL8 receptors using a combination of extracellular loops that differ from those bound by IL8. To test the hypothesis that rBmAsnRS might induce an anti-inflammatory effect in vivo, we studied the effects of rBmAsnRS in an established murine colitis model using T-cell transfer mice. T cell transfer colitis mice treated intraperitoneally with 100 μg of rBmAsnRS four times over two weeks, showed resolution of cellular infiltration in the colonic mucosa, along with induction of a CD8(+) cellular response. In addition, rBmAsnrs induced a rise in IL10 production from CD3+, LPS- and CPG-stimulated splenic cells. In summary, this work demonstrates a novel anti-inflammatory nematode protein, supports the Hygiene Hypothesis and supports continued refinement of alternative immunotherapies for treatment of IBD.
Anti-TNF-α are used in the treatment of rheumatic diseases not responsive to first-line regimens. Data on the safety of anti-TNF-α in HIV-infected patients are scarce and conflicting. We describe a case of septic shock and multiorgan failure occurred after etanercept initiation and influenza vaccination in a HIV-infected-woman with rheumatoid arthritis.
Lsr 2 protein of Mycobacterium leprae (ML) and its synthetic peptides were shown earlier to elicit lymphoproliferation and interferon γ (IFN γ) release by peripheral blood mononuclear cells (PBMC) of lepromatous leprosy patients (1). PBMC from 16 lepromatous patients undergoing erythema nodosum leprosum (ENL, Type 2) and 5 with reversal reactions (RR, Type 1) were stimulated with ML, recombinant Lsr 2 and six end to end synthetic peptides ( A-F) spanning the Lsr 2 sequence. During reaction all ENL patients showed lymphoproliferation (> 2 stimulation index) to peptides A and F with other peptides eliciting responses in 75-88% of the subjects. Both lymphoproliferation and IFN γ release for peptide E was significantly higher compared to peptides, B,C and recombinant Lsr 2 (p< 0.05, Wilcoxon signed rank test) in PBMC cultures. Five RR patients also showed enhanced lymphoproliferative responses and IFN γ release to Lsr 2, ML and peptide E. Six months post reaction, 14 ENL patients continued to exhibit responses to Lsr 2 and its peptides with the highest responses being elicited by peptide E. However, 5 subjects showed no lymphoproliferation and reduced IFN γ release to Lsr 2 peptides (p< 0.001, Kruskal Wallis test) but responded to recombinant Lsr 2. Six ENL patients had HLA A*68.01 which showed high peptide binding scores of 20-21 for peptides E, B, C using STFPEITHI program. Eleven patients had HLA-DRB1*1501 and *1502 which had high binding scores for peptides C and E. Thus, Lsr 2 and its peptides are recognized in leprosy reactions during and well after subsidence of clinical signs.
Clostridium difficile produces two major virulence toxins, Toxin A (TcdA) and Toxin B (TcdB). Anti-toxin antibodies, especially neutralizing antibodies, have been shown to be associated with lower incidence of C. difficile infection (CDI) recurrence and antibody levels are predictive of asymptomatic colonization. The development of an assay to detect the presence of neutralizing antibodies in animal and human sera for the evaluation of vaccine efficacy is highly desired. We have developed such an assay which allows for the quantification of the effect of toxins on eukaryotic cells in an automated manner. We describe here the optimization of this assay to measure toxin potency as well as Neutralizing Antibody (NAb) activity against C. difficile toxins using Design of Experiment (DOE) methodology. Toxin concentration and source, cell seeding density, and sera-toxin pre-incubation time were optimized in the assay using Vero cells. The assay was shown to be robust, and to produce linear results across a range of antibody concentrations. It can be used to quantify neutralizing antibodies in sera of monkeys and hamsters immunized with C. difficile toxoid vaccines. This assay was shown to correlate strongly with traditional assays which rely on labor intensive methods of determining neutralizing antibody titers by visual microscopic inspection of intoxicated cell monolayers. This assay has utility for the selection and optimization of C. difficile vaccine candidates.
Hydatidosis is a public health problem in many parts of the world, and improvement in diagnosis of the disease is still being pursued. Protoscoleces of Echinococcus granulosus were isolated from hydatid cysts collected from naturally infected sheep slaughtered in abattoirs in Iran. Sonicated extract of protoscolex was subjected to two-dimensional gel electrophoresis and western blot analysis. Primary antibodies were from serum samples from 130 hydatidosis patients, 38 individuals infected with other parasitic infections and 30 healthy people; while peroxidase (HRP)-conjugated anti-human IgG and IgG4 were used as secondary antibodies. The recombinant form of the identified protein was produced and tested for its sensitivity and specificity for the detection of human hydatidosis. An antigenic band of ∼ 60 kDa was found to be sensitive (82%) and specific (100%) for the detection of hydatidosis when probed with anti-human IgG4-HRP, while the sensitivity and specificity were 33% and 100%, respectively, with anti-human IgG-HRP. By mass-spectrometry, the band was identified as protoscolex tegument paramyosin. The sensitivity and specificity of full-length paramyosin-recombinant protein in IgG4 blots were found to be 86% and 98%, respectively. In conclusion, IgG4 detection of Echinococcus granulosus paramyosin was found to be useful for the diagnosis of human hydatidosis.
In Korean field conditions, coinfection with porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) is most commonly observed in porcine respiratory disease complex (PRDC). Despite the wide use of PCV2 vaccination, PRDC remains a serious respiratory problem. Thus, the objective of this study was to determine and compare the efficacy of 4 one-dose PCV2 vaccines on 3-week-old pigs with an experimental PCV2-PRRSV challenge at 17 weeks post vaccination. Regardless of which commercial PCV2 vaccine was used, vaccination of piglets at 3 weeks of age was efficacious against co-challenge of PCV2 and PRRSV based on growth performance and PCV2-associated lesions. However, the inactivated chimeric PCV2 1-2 and PCV2 vaccine induced higher PCV2-specific neutralizing antibody titers and PCV2-specific interferon-γ-secreting cells and lower PCV2 viremia compared to the two PCV2 subunit vaccines. PCV2 vaccination of piglets at 3 weeks of age was effective in reducing PCV2 viremia and PCV2-associated lesions during the finishing period, which is an age frequently affected by PRDC caused by coinfection with PCV2 and PRRSV in Korean field conditions.
Leptospirosis is a serious zoonosis that is under-diagnosed with limited access to laboratory facilities in Southeast Asia, Central and South America and Oceania. Timely diagnosis of locally distributed serovars of high virulence is crucial for successful care and outbreak management. Using pooled patients' sera an expression gene library of a virulent Leptospira interrogans serovar Autumnalis strain N2 isolated in South India was screened. The identified genes were characterized and the purified recombinant proteins were used as antigens in IgM ELISA either singly or in combination. Sera (n = 118) from cases of acute leptospirosis along with sera (n = 58) from normal healthy subjects were tested for reactivity with the identified proteins in an ELISA designed to detect specific IgM. We have identified nine immunoreactive proteins ArgC, RecA, GlpF, FliD, TrmD, RplS, RnhB, Lp28.6, and Lrr44.9 which were found to be highly conserved among pathogenic leptospires. Apparently the proteins ArgC, RecA, GlpF, FliD, TrmD and Lrr44.9 are expressed during natural infection of the host and undetectable in in vitro cultures. Among all the recombinant proteins used as antigens in IgM ELISA, ArgC had the highest sensitivity and specificity of 89.8% and 95.5% respectively for the conclusive diagnosis of leptospirosis. The use of ArgC and RecA in combination for IgM ELISA increased the sensitivity and specificity to 95.7 and 94.9% respectively. ArgC and RecA thus elicited specific IgM responses and therefore effective in laboratory confirmation of Leptospira infection.
We report final event-driven analysis data on the immunogenicity and efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in young women aged 15-25 years from the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT001226810). The total vaccinated cohort (TVC) included all randomised participants who received at least one vaccine dose (vaccine, n=9319; control, n=9325) at months 0, 1 and/or 6. The TVC-naïve (vaccine, n=5822; control, n=5819) had no evidence of high-risk HPV infection at baseline approximating adolescent girls targeted by most HPV vaccination programmes. Mean follow-up was approximately 39 months after the first vaccine dose in each cohort. At baseline, 26% of women in the TVC had evidence of past and/or current HPV-16/18 infection. HPV-16 and HPV-18 antibody titres post-vaccination tended to be higher among 15-17 year-olds than 18-25 year-olds. In the TVC, vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 1 or greater (CIN1+), CIN2+ and CIN3+ associated with HPV-16/18 was 55.5% (96.1% CI: 43.2, 65.3), 52.8% (37.5, 64.7) and 33.6% (-1.1, 56.9). VE against CIN1+, CIN2+ and CIN3+ irrespective of HPV DNA was 21.7% (10.7, 31.4), 30.4% (16.4, 42.1) and 33.4% (9.1, 51.5) and consistently significant only in 15-17 year-old women (27.4% [10.8, 40.9], 41.8% [22.3, 56.7] and 55.8% [19.2, 76.9]). In the TVC-naïve, VE against CIN1+, CIN2+ and CIN3+ associated with HPV-16/18 was 96.5% (89.0, 99.4), 98.4% (90.4, 100) and 100% (64.7, 100); and irrespective of HPV DNA was 50.1% (35.9, 61.4), 70.2% (54.7, 80.9) and 87.0% (54.9, 97.7). VE against 12-month persistent infection with HPV-16/18 was 89.9% (84.0, 94.0) and against HPV-31/33/45/51 was 49.0% (34.7, 60.3). In conclusion, vaccinating adolescents before sexual debut has a substantial impact on the overall incidence of high-grade cervical abnormalities, and catch-up vaccination up to 18 years of age is most likely effective.